1.Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway
Qinwen TAN ; Jingjing HUANG ; Ruixi ZHONG ; Yuanqin DU ; Jian XU ; Jinli NONG ; Yujiao PENG
Journal of Clinical Hepatology 2025;41(2):300-306
ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation, migration, and aerobic glycolysis of hepatocellular carcinoma (HCC) using cell experiments, as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected, and Sprague-Dawley rats were randomly divided into blank serum group, inhibitor group, and high-, middle-, and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells; glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells; RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression, related proteins, and phosphorylation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group, the Biejia Decoction Pill groups had significant reductions in OD value, migration rate during different periods of time, glycolytic rate-limiting enzymes (hexokinase, phosphofructokinase, pyruvate kinase), and glycolytic metabolites (pyruvate, lactic acid, ATP) (all P<0.05). RT-qPCR results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR, and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT (all P<0.05). Western blot results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins, and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins (all P<0.05). ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells, thereby inhibiting their proliferation and migration, possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.
2.Transzonal Projections and Follicular Development Abnormalities in Polycystic Ovary Syndrome
Di CHENG ; Yu-Hua CHEN ; Xia-Ping JIANG ; Lan-Yu LI ; Yi TAN ; Ming LI ; Zhong-Cheng MO
Progress in Biochemistry and Biophysics 2025;52(10):2499-2511
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.
3.Clinical Efficacy of Fuzheng Huaji Longbi Decoction in Treating Benign Prostatic Hyperplasia with Syndrome of Healthy Qi Deficiency and Blood Stasis
Ninghua LI ; Zulong WANG ; Chenming ZHANG ; Xiao LI ; Rubing CHEN ; Qi ZHANG ; Zhong HUA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):77-82
ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia (BPH) in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups, with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets, and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks, the international prostate symptom score (IPSS), quality of life (QOL) score, residual urine volume (RUV), maximum urinary flow rate (Qmax), TCM syndrome score, TCM symptom score, electrocardiogram, and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment, the total response rate in the control group was 63.64% (28/44), which was lower than that (84.44%, 38/45) in the observation group (χ2=5.026, P<0.05). The clinical efficacy in the observation group was higher than that in the control group (Z=-2.17, P=0.030). The treatment in both groups decreased the IPSS, QOL score, RUV, and TCM syndrome scores and increased the Qmax (P<0.05). Moreover, the observation group had lower IPSS, QOL score, RUV, and TCM syndrome score (P<0.05) and higher Qmax than the control group after treatment (P<0.05). The treatment in the observation group decreased all the TCM symptom scores (P<0.05), while that in the control group only decreased the frequency of urination at night and the scores of dysuria, weak urine stream, and post-urinary drainage (P<0.05). After treatment, the observation group had lower frequency of urination at night and lower scores of mental fatigue, cold limbs, lower abdominal discomfort, and loose stool than the control group (P<0.05). No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life, being a safe and reliable choice for clinical application.
4.Clinical Efficacy of Traditional Chinese Medicine Suppository Combined with Yishen Tongluo Qingkang Decoction in Treatment of Immune Infertility
Zhong HUA ; Pengchao LI ; Ninghua LI ; Zixue SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):114-119
ObjectiveTo evaluate the clinical efficacy and safety of traditional Chinese medicine (TCM) suppository combined with Yishen Tongluo Qingkang decoction in the treatment of immune infertility. MethodA total of 116 patients meeting the inclusion criteria of this study were randomly divided into an observation group (58 cases) and a control group (58 cases). The observation group was treated with TCM suppository combined with Yishen Tongluo Qingkang decoction,and the control group was treated with prednisone acetate tablets. Both groups were treated for 12 weeks and followed up six months after treatment. Semen samples of the patients were collected before and after treatment,and the pregnancy status of their spouses,negative conversion rate of seminal plasma anti-sperm antibody (AsAb),sperm concentration,motility,percentage of forward motile sperm,sperm acrosin activity, and incidence of adverse reactions were compared between the two groups. ResultA total of 104 patients completed the study,including 53 cases in the observation group and 51 cases in the control group. Before treatment,the baseline data of the two groups were balanced. After treatment,the total effective rate of the observation group was 92.45%,which was higher than that of the control group (76.47%)(P<0.05),and the negative conversion rate of AsAb in the observation group was higher than that in the control group,but the difference was not statistically significant. After treatment,the sperm motility, percentage of forward motile sperm, and sperm acrosin activity increased in the two groups(P<0.05),and the sperm concentration in the observation group increased (P<0.05). There was no significant difference in sperm concentration in the control group. After treatment,the sperm concentration,motility,percentage of forward motile sperm, and acrosin activity in the observation group were better than those in the control group (P<0.05). During the trial,the incidence of adverse reactions in the observation group was lower than that in the control group (P<0.05). ConclusionTCM suppository combined with Yishen Tongluo Qingkang decoction can significantly increase the negative conversion rate of AsAb and improve the quality of semen in patients with immune infertility.
5.Stick-point Sinew-soothing and Bone-setting Manipulation for Scapulohumeral Periarthritis: a Randomised Controlled Trial
Haijun JIANG ; Xianzhong BU ; Yuanming ZHONG ; Jianfeng HUANG ; Baohe YIN ; Dingshan CEN
Journal of Traditional Chinese Medicine 2024;65(3):292-298
ObjectiveTo explore the clinical effectiveness and safety of stick-point sinew-soothing and bone-setting manipulation for scapulohumeral periarthritis. MethodsUsing prospective randomised controlled trial method, 60 cases of patients with scapulohumeral periarthritis were collected and randomly divided into 30 cases each in control group and trial group. Both groups of patients were orally treated with celecoxib, on the basis of which the control group was treated with traditional bonesetting manipulation once every other day for 14 days, while the trial group was treated with stick-point sinew-soothing and bone-setting manipulation once every 3~5 days for 14 days. Both groups were treated for 2 courses. The main observation indexes were pain visual analogue scale (VAS) score and shoulder pain and dysfunction index (SPADI), which were evaluated once before treatment and after 2 and 4 weeks of treatment. The secondary effectiveness indicators included the university of California at Los Angeles shoulder rating scale (UCLA), traditional Chinese medicine syndrome score (including symptom scores as joint pain, pain in a fixed place, activity limitation, local stiffness), and serum interleukin (IL-6) and tumour necrosis factor α (TNF-α) levels before and after the treatment, in order to evaluate the clinical effectiveness, and to record the adverse reactions that occurred in the process of diagnosis and treatment. ResultsCompared with the groups before treatment, the pain VAS score, SPADI and scores of joint pain, pain with a fixed place, activity limitation and local stiffness were lower, UCLA score was higher, and serum IL-6 and TNF-α levels were lower at 4 weeks of treatment in the two groups (P<0.05). When comparing the two groups between the groups at 2 and 4 weeks of treatment, the pain VAS score, SPADI and TCM scores of each symptom in the study group were lower than those in the control group, the UCLA score was higher than those in the control group (P<0.01), and the serum IL-6 and TNF-α levels were lower than those in the control group at 4 weeks of treatment (P<0.01). The clinical effectiveness rate of the study group was 66.67%, which was significantly higher than that of the control group, which was 40.00% (P = 0.038). No adverse reactions were seen in both groups during the study. ConclusionCompared with the traditional massage manipulation, the treatment of scapulohumeral periarthritis with stick-point sinew-soothing and bone-setting manipulation has more advantages in relieving pain symptoms, reducing inflammatory reaction, and promoting the recovery of shoulder joint function.
6.The Effect and Mechanism of Mitophagy on Insulin Resistance
Yu-Hua CHEN ; Biao ZHENG ; Di CHENG ; Yu-Lin HE ; Zhong-Cheng MO
Progress in Biochemistry and Biophysics 2024;51(4):772-784
Mitophagy, a highly precise form of autophagy, plays a pivotal role in maintaining cellular homeostasis by selectively targeting and eliminating damaged mitochondria through a process known as mitophagy. Within this tightly regulated mechanism, dysfunctional mitochondria are specifically delivered to lysosomes for degradation. Disruptions in mitophagy have been implicated in a diverse range of pathological conditions, spanning diseases of the nervous system, cardiovascular system, cancer, aging, and metabolic syndrome. The elucidation of mitophagy’s impact on cardiovascular disorders, liver diseases, metabolic syndromes, immune dysfunctions, inflammatory conditions, and cancer has significantly advanced our understanding of the complex pathogenesis underlying these conditions. These studies have shed light on the intricate connections between dysfunctional mitophagy and disease progression. Among the disorders associated with mitochondrial dysfunction, insulin resistance (IR) stands out as a prominent condition linked to metabolic disorders. IR is characterized by a diminished response to normal levels of insulin, necessitating higher insulin levels to trigger a typical physiological reaction. Hyperinsulinemia and metabolic disturbances often coexist with IR, primarily due to defects in insulin signal transduction. Oxidative stress, stemming from mitochondrial dysfunction, exerts dual effects in the context of IR. Initially, it disrupts insulin signaling pathways and subtly contributes to the development of IR. Additionally, by inducing mitochondrial damage and autophagy, oxidative stress indirectly impedes insulin signaling pathways. Consequently, mitophagy acts as a protective mechanism, encapsulating damaged or dysfunctional mitochondria through the autophagy-lysosome pathway. This efficient process eliminates excessive oxidative stress reactive. The intricate interplay between mitochondrial function, oxidative stress, mitophagy, and IR represents a captivating field of investigation in the realm of metabolic disorders. By unraveling the underlying complexities and comprehending the intricate relationships between these intertwined processes, researchers strive toward uncovering novel therapeutic strategies. With a particular focus on mitochondrial quality control and the maintenance of redox homeostasis, these interventions hold tremendous potential in mitigating IR and enhancing overall metabolic health. Emerging evidence from a myriad of studies has shed light on the active involvement of mitophagy in the pathogenesis of metabolic disorders. Notably, interventions such as exercise, drug therapies, and natural products have been documented to induce mitophagy, thereby exerting beneficial effects on metabolic health through the activation of diverse signaling pathways. Several pivotal signaling molecules, including AMPK, PINK1/Parkin, BNIP3/Nix, and FUNDC1, have been identified as key regulators of mitophagy and have been implicated in the favorable outcomes observed in metabolic disorders. Of particular interest is the unique role of PINK1/Parkin in mitophagy compared to other proteins involved in this process. PINK1/Parkin exerts influence on mitophagy through the ubiquitination of outer mitochondrial membrane proteins. Conversely, BNIP3/Nix and FUNDC1 modulate mitophagy through their interaction with LC3, while also displaying certain interrelationships with each other. In this comprehensive review, our objective is to investigate the intricate interplay between mitophagy and IR, elucidating the relevant signaling pathways and exploring the treatment strategies that have garnered attention in recent years. By assimilating and integrating these findings, we aim to establish a comprehensive understanding of the multifaceted roles and intricate mechanisms by which mitophagy influences IR. This endeavor, in turn, seeks to provide novel insights and serve as a catalyst for further research in the pursuit of innovative treatments targeting IR.
7.Evaluation and analysis of bleeding risk of anticoagulation therapy in severe non-ICU patients with COVID-19 based on heparinase-modified TEG
Ying ZHONG ; Xianwen HUANG ; Chunfeng LIANG
Chinese Journal of Blood Transfusion 2024;37(3):312-318
【Objective】 To investigate the clinical application of heparinase-modified TEG (hmTEG) in evaluating coagulation status and monitoring anticoagulant therapy in severe non-ICU patients with COVID-19. 【Methods】 The clinical data of severe non-ICU patients with COVID-19 confirmed to be infected with novel coronary disease (SARS-CoV-2) from December 2022 to May 2023 were analyzed retrospectively. The patients were divided into therapeutic dose group and prophylactic dose group according to the initial dose of enoxaparin. The changes of platelet count, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, D-dimer, TEG and hmTEG before and after heparin treatment were compared between the two groups, so as to evaluate the changes of coagulation function and bleeding risk of COVID-19 severe non-ICU patients after anticoagulation with different doses of heparin. 【Results】 A total of 179 severe non-ICU patients with COVID-19 were enrolled in this study, including 102 patients in therapeutic dose group and 77 patients in prophylactic dose group. Before receiving heparin anticoagulation, except for age(63.4±11.6 vs 59.8±9.1) D-dimer(678 ng/mL vs 621 ng/mL) and MA values [(69.1±10.2)mm vs (65.6±8.5)mm], there were no statistical differences in platelet count, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, R value, K time, α angle and coagulation index (CI) between the therapeutic dose group and the prophylactic dose group (P>0.05). After receiving heparin anticoagulation, there were significant differences in CKR value [(12.2±4.1)min vs (10.2±3.3)min] and CKHR value [(8.1±3.2)min vs (7.1±2.6)min] between therapeutic dose group and prophylactic dose group (P<0.05), but no significant differences in other parameters between groups (P>0.05). Meanwhile, the proportion of heparin overdose in the therapeutic dose group was significantly higher than that in the prophylactic dose group 15.69%(16/102) vs 5.19%(4/77)(P<0.05). However, there was no difference in the incidence of VTE events 2.35 %(2/85) vs 2.78%(2/72), gastrointestinal bleeding 2.35%(2/85) vs 1.39%(1/72), ICU admission 4.71%(4/85) vs 4.17%(3/72) and death events 3.53%(3/85) vs 2.78%(2/72) between the two groups (P>0.05). 【Conclusion】 In the current epidemic trend of COVID-19, in order to reduce the occurrence of bleeding events, the heparin dose should be selected more carefully in the prevention of thrombosis in severe non-ICU patients with COVID-19. The individualized assessment of bleeding risk by hmTEG is more conducive to the adjustment and control of heparin dose.
8.Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice
Ying Li MENG ; Fu Wen TAO ; Jing LI ; Min ZHU ; Bin De ZHONG ; Jing ZHOU ; Xue QIN ; Guo Rong WEI
Biomedical and Environmental Sciences 2024;37(1):19-30
Objective The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.Methods We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg·day) and 50 μg/(kg·day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing. Results Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment. Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.
9.Study on in vitro anti-inflammatory effects and mechanisms of oblongifolins A extracted from Garcinia oblon-gifolia
Xueshan LI ; Guiming QIN ; Huiying SHI ; Xiaoqin ZOU ; Jie FENG ; Xiaobin ZHONG
China Pharmacy 2024;35(10):1209-1214
OBJECTIVE To investigate the in vitro anti-inflammatory effects and mechanisms of oblongifolins A (OA) extracted from Garcinia oblongifolia. METHODS RAW264.7 cells were used as the research subject and divided into control group (0.5% DMSO), lipopolysaccharide (LPS) group (1 μg/mL), DEX group (10 µmol/L DEX+1 μg/mL LPS), and low-, medium-, and high-concentration groups of OA (7.5, 15, 30 µmol/L OA+1 μg/mL LPS). Except for the control group, the remaining groups were first stimulated with LPS for 1 hour and then mixed with drugs for 24 hours. The morphological changes of cells were observed in each group. The contents of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, IL-4 and IL-10 were detected in cells of each group; mRNA expression levels of TNF-α, IL-6 and IL-1β were measured. The expression of key proteins in the nuclear factor κB (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathways in each group, as well as the nuclear translocation of NF-κB p65 and Nrf2 proteins in control group, LPS group and OA high-concentration group, were detected. RESULTS Compared to the LPS group, the number of spindle-shaped and irregular cells gradually decreased in OA groups, the contents of NO, ROS (except for OA low-concentration group), TNF-α, IL-6 and IL-1β, the mRNA expressions of TNF-α, IL-6 (except for OA low-concentration group) and IL-1β as well as the protein expressions of phosphorylated NF-κB p65 (p-NF-κB p65), p-IκBα, and Kelch-like ECH-associated protein 1 (Keap1) were decreased significantly (P<0.05). The contents of IL-4 and IL-10, protein expressions of IκBα, Nrf2 (except for OA low- and medium-concentration groups), HO-1 (except for OA low-concentration group) and NQO1 were all increased significantly (P<0.05). OA of high concentration could inhibit NF-κB p65 protein nuclear translocation and promote Nrf2 protein nuclear translocation. CONCLUSIONS OA can suppress LPS-induced inflammation in RAW264.7 macrophages. The underlying molecular mechanism likely entails the inhibition of the NF-κB signaling pathway, the activation of the Nrf2 signaling pathway and the reduction of ROS and inflammatory factor release.
10.Advances in the role of macrophages in the immunoregulatory treatment mechanism of uveitis
International Eye Science 2024;24(7):1068-1072
Uveitis is a common and refractory inflammatory blinding disease involving the uvea, retina, retinal vessels, and vitreous body. Its occurrence is related to the imbalance of immune mechanisms in various cell subpopulations. Macrophages play a central role in the body's innate immune system and can effectively clear pathogenic bacteria from the body. In stress responses, macrophages can participate in the body's pathogen response and inflammation regulation through polarization. Therefore, in order to systematically understand the important role of macrophage polarization balance in the immune regulation mechanism of uveitis, this article mainly links it with the occurrence and development of uveitis disease through the study of the source recognition of macrophages and the mechanism pathway, and finally summarizes the progress of related diagnosis and treatment.

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