1.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
2.Short-term efficacy of low-dose transscleral cyclophotocoagulation for persistent ocular hypertension in acute angle-closure glaucoma
Qiaoyun LI ; Yong JIA ; Baike ZHANG ; Xiaojing GUO ; Cong LU ; Xinli WEI ; Xuemin TIAN
International Eye Science 2026;26(4):706-710
AIM: To evaluate the safety and efficacy of low-dose transscleral cyclophotocoagulation(TSCP)in the management of persistent ocular hypertension after an acute attack of angle-closure glaucoma(AACG).METHODS:This retrospective study enrolled patients diagnosed with persistent ocular hypertension after an acute AACG attack at the No.988 Hospital of the Joint Logistics Support Force of the Chinese PLA between September 2023 and September 2024. All patients underwent low-dose TSCP using a semiconductor diode laser. Subsequent cataract surgery combined with goniosynechialysis was performed once intraocular pressure(IOP)was stabilized. Changes in anterior chamber depth(ACD), best-corrected visual acuity(VA), and IOP were compared before and after TSCP, as well as before and after phacoemulsification. Post-TSCP complications were also documented.RESULTS: A total of 21 patients(21 eyes)were enrolled, including 8 males and 13 females, with a mean age of 67.95±7.25 y. Compared with pre-cyclophotocoagulation values, ACD increased significantly at 3 d post-TSCP(1.49±0.18 vs 1.22±0.21 mm; P<0.001). BCVA and IOP decreased significantly at 1 d post-TSCP, pre-phacoemulsification, 1 wk post-phacoemulsification, and 1 mo post-phacoemulsification compared with pre-TSCP IOP(all P<0.01). Regarding postoperative complications, 2 eyes experienced pain on the day of the procedure, 5 eyes developed mild corneal endothelial folds, 2 eyes exhibited moderate anterior chamber inflammatory reaction, and 12 eyes showed shallow ciliary body detachment. No serious complications occurred during the 1-month follow-up period.CONCLUSION:Low-dose TSCP appears to be an effective bridging therapy for patients with persistent ocular hypertension following an AACG attack. It facilitates rapid IOP reduction, alleviates symptoms, and helps preserve visual function with a favorable safety profile, thereby reducing the risks associated with subsequent intraocular surgery.
3.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
4.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
5.Comparative Transcriptomic and Metabolomic Analyses Reveal the Mechanism by Which Foam Macrophages Restrict Survival of Intracellular Mycobacterium Tuberculosis.
Xiao PENG ; Yuan Yuan LIU ; Li Yao CHEN ; Hui YANG ; Yan CHANG ; Ye Ran YANG ; Xuan ZHANG ; An Na JIA ; Yong Bo YU ; Yong Li GUO ; Jie LU
Biomedical and Environmental Sciences 2025;38(7):781-791
OBJECTIVES:
This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival.
METHODS:
An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.
RESULTS:
Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.
CONCLUSIONS
FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology*
;
Transcriptome
;
Metabolomics
;
Foam Cells/microbiology*
;
Humans
;
Metabolome
;
Tuberculosis/microbiology*
;
Gene Expression Profiling
6.Analysis of Tongue and Face Image Features of Anemic Women and Construction of Risk-Screening Model.
Hong Yuan FU ; Yi CHUN ; Ya Han ZHANG ; Yu WANG ; Yu Lin SHI ; Tao JIANG ; Xiao Juan HU ; Li Ping TU ; Yong Zhi LI ; Jia Tuo XU
Biomedical and Environmental Sciences 2025;38(8):935-951
OBJECTIVE:
To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance.
METHODS:
A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated.
RESULTS:
Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818].
CONCLUSION
Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans
;
Female
;
Tongue/diagnostic imaging*
;
Adult
;
Anemia/diagnosis*
;
Middle Aged
;
Face/diagnostic imaging*
;
Young Adult
;
Machine Learning
7.Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction(2025)
Chunhua ZHANG ; Weiwei BIAN ; Congmin WANG ; Lin SHEN ; Yong MIAO ; Na LIU ; Shan JIA ; Junhong AN ; Hongxia WANG ; Dongmei ZHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1606-1613
To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice
8.Four Weeks of HIIT Modulates Lactate-mediated Synaptic Plasticity to Improve Depressive-like Behavior in CUMS Rats
Yu-Mei HAN ; Zi-Wei ZHANG ; Jia-Ren LIANG ; Chun-Hui BAO ; Jun-Sheng TIAN ; Shi ZHOU ; Huan XIANG ; Yong-Hong YANG
Progress in Biochemistry and Biophysics 2025;52(6):1499-1510
ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, Smax) alternated with one minute at low speed (50%-55% Smax), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.
9.Analysis of Animal Models of Autoimmune Thyroiditis Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Sifeng JIA ; Zhuo ZHANG ; Yuyu DUAN ; Keqiu YAN ; Xinhe ZUO ; Yang LI ; Yong ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):235-243
ObjectiveAutoimmune thyroiditis (AIT) is a complex and immune-mediated disorder, with no established treatment protocol. Both Western and traditional Chinese medicine (TCM) focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM, using a novel evaluation method. Additionally, it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models, using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM, and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization, iodine induction, heterologous thyroid antigen immunization, and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%, 60%, 54%, and 63%, with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common, with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory, meeting the surface and structural effectiveness criteria of Western medicine. However, there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine, with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine, creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM, providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.
10.Efficacy comparison of foldable capsular body with scleral buckling in treating experimental retinal detachment
Yifan DONG ; Baike ZHANG ; Yong JIA ; Fan YANG ; Lisha GUO ; Xiangyang ZHANG ; Cong LU ; Zhonghao ZHANG ; Haiyan WU ; Xuemin TIAN
International Eye Science 2025;25(10):1566-1573
AIM: To compare the effectiveness of foldable capsular body(FCB)with traditional scleral buckling(SB)in the treatment of experimental retinal detachment animal models.METHODS: After successfully establishing rhegmatogenous retinal detachment(RRD)animal models, 24 New Zealand white rabbits were randomly divided into three groups(RRD models group, SB group, and FCB group), with 8 rabbits in each group. The FCB and SB groups underwent SB and FCB surgeries for the RRD animal models, while the RRD models group only consists of RRD models without any surgical intervention during the follow-up period. The follow-up duration was 3 mo. Wide-field neonatal fundus imaging system and ophthalmic B-ultrasound were used to assess the fundus conditions before and after surgery. The Icare® TONOVET Plus tonometer was utilized to evaluate intraocular pressure changes before and after surgery. The Eaton and Draize scoring systems were selected to monitor postoperative inflammatory reactions.RESULTS: The retinal reattachment rates in the FCB and SB groups were 87.5% and 75.0%, respectively, with no statistically significant difference between the groups(P>0.05). The intraocular pressure in both the FCB and SB groups increased postoperatively compared to preoperative levels(P<0.01), and there were no significant differences in intraocular pressure at any time points during the follow-up period between the groups(P>0.05). The intraocular pressure in the RRD models group remained at a low level throughout the follow-up period. The average surgical time for the FCB group was 16.87±2.29 min, which was shorter than 46.25±4.74 min in the SB group(t=-15.166, P<0.001). According to the Eaton and Draize scoring systems, the FCB group had lower grades of conjunctival hyperemia and edema in the early postoperative period compared to the SB group, indicating milder inflammatory reactions(P<0.05).CONCLUSION: Both FCB and SB are effective in treating experimental RRD. Compared to SB, FCB is simpler to operate, and also has a shorter surgical time and milder postoperative inflammatory reactions.

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