1.The Structure and Function of The YopJ Family Effectors in The Bacterial Type III Secretion System
Ao-Ning LI ; Wen-Bo LI ; Yu-Ying LU ; Min-Hui ZHU ; Yu-Long QIN ; Yong ZHAO ; Zhao-Huan ZHANG
Progress in Biochemistry and Biophysics 2026;53(3):516-533
The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP6), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP6-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.
2.Effectiveness of generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity
Qiaoyun YAN ; Min LI ; Yawen YAN ; Yaqing NI ; Yun GU ; Jiawen QIN ; Haiping YU ; Haitao ZHANG ; Liming ZHAO
Chinese Journal of Clinical Medicine 2026;33(1):16-23
Objective To explore the effectiveness of the generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity. Methods A quasi-randomized controlled trial study was conducted involving 6 junior nurses, 6 senior nurses and the MedGo model from January 1, 2025 to March 31, 2025 at the Emergency Internal Medicine Ward of Shanghai East Hospital Affiliated to Tongji University. Clinical data of 120 elderly patients with multimorbidity were analyzed to compare the performance of the three groups in four tasks (nursing diagnosis assessment, nursing intervention formulation, complication identification, and complication prevention) from three evaluation dimensions: decision-making time consumption, decision accuracy, and decision-making quality. Results In terms of decision-making time, the senior nurse group completed all four tasks faster than the junior nurse group (P<0.01), and the MedGo group completed all four tasks faster than the junior nurse group (P<0.001) and the senior nurse group (P<0.001). In terms of decision-making accuracy, senior nurse group scored higher than junior nurse group in all four tasks (P<0.001), while the MedGo group outperformed the senior nurse group only in complication identification (P<0.001). In terms of decision-making quality, the MedGo group scored higher than junior nurse group (P<0.001) and senior nurse group (P<0.001) in all four tasks. Conclusions The MedGo model demonstrates advantages of high efficiency, accuracy, and quality in nursing decision-making for elderly patients with multimorbidity; senior nurses outperform junior nurses in decision-making, providing diverse references for clinical nursing decision-making.
3.Analysis of Quality Changes of Small Packaged Alismatis Rhizoma Decoction Pieces Under Different Packaging and Storage Conditions
Gaoting YANG ; Rui XIAN ; Zimin WANG ; Zongyi ZHAO ; Zhiqiong LAN ; Xiaoli PAN ; Min LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):179-188
ObjectiveTo screen suitable packaging and storage conditions for small packaged Alismatis Rhizoma decoction pieces, laying the foundation for developing standardized storage, maintenance techniques and determining shelf life. MethodsUsing the accelerated stability test method, the small packaged decoction pieces of Alismatis Rhizoma were placed in polyethylene plastic bags, aluminum foil polyethylene composite bags, and cowhide coated paper bags under temperature of (40±2) ℃ and relative humidity of (75±5)% conditions, the quality testing was conducted at the end of the 0th, 1st, 2nd, 3rd, and 6th month, respectively. Using long-term stability test method, an orthogonal experiment was designed to investigate storage conditions, packaging materials, and packaging methods. At the end of the 0th, 1st, 3rd, 6th, 9th, 12th, 18th, and 24th month, the quality of small packaged Alismatis Rhizoma decoction pieces was tested under different packaging and storage conditions(including 2 packaging methods:vacuum packaging and sealed packaging, 3 storage conditions:room temperature, cool, and modified atmosphere, 3 packaging materials:cowhide coated paper bag, aluminum foil polyethylene composite bag, and polyethylene plastic bag). Then, the G1-entropy weight method combined with orthogonal experiment was used to analyze the quality changes of the decoction pieces under different packaging and storage conditions to identify optimal packaging and storage conditions. The quality testing indicators for Alismatis Rhizoma decoction pieces were expanded beyond those specified in the 2020 edition of the Pharmacopoeia of the People's Republic of China. In addition to the existing indicators(characteristics, moisture content, extractives, and the total content of 23-acetyl alisol B and 23-acetyl alisol C), new indicators including color value, water activity, total triterpenoid content, and alisol B content have been added. ResultsThe accelerated stability test results indicated that the quality of small packaged Alismatis Rhizoma decoction pieces was more stable when packaged in aluminum foil-polyethylene composite materials compared to cowhide-coated paper bags and polyethylene plastic bags. Analysis of the long-term stability test results using the G1-entropy weight method combined with orthogonal experiment revealed that storage conditions had the greatest impact on both raw and salt-processed products, followed by packaging materials, while the packaging method had the least influence. For both types of small packaged Alismatis Rhizoma decoction pieces, modified atmosphere storage demonstrated superior efficacy compared to cool storage or room temperature storage. Storage in aluminum foil-polyethylene composite bags was superior to polyethylene plastic bags or cowhide-coated paper bags. However, the stability of sealed raw products was better than vacuum-packed ones, whereas vacuum-packed salt-processed products exhibited greater stability than their sealed counterparts. ConclusionBased on the results of the quality changes of small packaged Alismatis Rhizoma decoction pieces under different storage conditions, it is recommended that the suitable storage packaging conditions for small packaged raw products are sealed packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage, and the suitable storage and packaging conditions for small packaged salt-processed products are vacuum packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage.
4.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
5.Dose response relationship between sleep duration and depressive symptoms risk in children and adolescents
DAI Chaolan, ZHAO Min, WANG Mingming, XI Bo
Chinese Journal of School Health 2026;47(1):80-84
Objective:
To investigate the association between sleep duration and depressive symptoms in children and adolescents, so as to provide scientific evidence for promoting mental health and preventing depression among relevant populations.
Methods:
A total of 2 192 children and adolescents aged 10-17 years with complete data from the 2018 China Family Panel Studies Database were included. Eight item Center for Epidemiologic Studies Depressive Scale(CES-D8) was used to assess participants depressive levels, and sleep duration was assessed via questionnaire. Multivariate Logistic regression model was used to analyze the association between different sleep duration categories and depressive symptom occurrence among children and adolescents. A restricted cubic spline(RCS) model analyzed the dose response relationship between sleep duration and the risk of depressive symptoms occurrence and segmented Logistic regression models to identify dose response effects.
Results:
Among the surveyed children and adolescents, 524(23.91%) exhibited depressive symptoms. Compared to those with sufficient sleep, children aged 10-12 years had a higher risk of depressive symptoms on average per day( OR =1.66, 95% CI =1.19-2.33) and during weekdays( OR =1.76, 95% CI =1.26-2.46), as well as in adolescents aged 13-17 years on a daily basis( OR =1.40,95% CI =1.06-1.85) and during weekdays( OR = 1.48,95% CI =1.12-1.95), and excessive sleep in adolescents on rest days was also significantly associated with higher risk of depressive symptoms( OR =1.65,95% CI =1.11-2.43)(all P <0.05). RCS analysis results indicate that children s sleep duration exhibits a linear negative correlation with the risk of depressive symptoms(all P nonlinear >0.05), while adolescents sleep duration showed a U shaped association with depressive symptoms(all P nonlinear <0.05) on a daily basis, during weekdays and weekends, with potential threshold effects at 10.00, 9.88, and 9.60 hours, respectively.
Conclusions
Sleep duration among children and adolescents is associated with depressive symptoms, with notable age related differeneces. It is recommended to develop targeted age specific interventions to reduce the risk of depressive symptoms in children and adolescents.
6.Umbrella review analysis of the safety and efficacy of vonoprazan in the treatment of peptic ulcers and post-ESD ulcers
Qingmei ZHU ; Min SHI ; Dongliang YANG ; Haixia ZHAO
China Pharmacy 2026;37(3):389-394
OBJECTIVE To analyze the safety and efficacy of vonoprazan (VPZ) in the treatment of peptic ulcer (PU) and post-endoscopic submucosal dissection (ESD) ulcers, providing evidence-based pharmaceutical evidence for clinical practice and medical decision-making. METHODS Retrieved from CNKI, Wanfang, VIP, CBM, PubMed, Embase, Web of Science, and the Cochrane Library, meta-analyses/systematic reviews related to VPZ in the treatment of PU and post-ESD ulcers were collected. Two researchers independently performed literature screening, data extraction, quality assessment of included studies, and evaluation of literature overlap. By employing the umbrella review analysis, a fresh meta-analysis was conducted on all relevant raw research data when a high degree of overlap was identified among the included studies. RESULTS A total of 17 meta-analyses were included, with quality ranging from high to very low; all outcome measures involved showed a very high level of overlap in the included meta-analyses (corrected covered area: 22.22%-100%). In the treatment of post-ESD ulcers, compared to proton pump inhibitor (PPI), VPZ significantly improved the ulcer healing rate at 4 weeks post-ESD [RR=1.27, 95%CI (1.03, 1.56), Z=2.21, P= 0.027] and the ulcer contraction rate post-ESD [MD=0.08, 95%CI (0.00, 0.16), Z=2.09, P=0.037], while significantly reducing the ulcer recurrence rate in patients with a history of PU [RR=0.49, 95%CI (0.32, 0.73), Z=3.49, P=0.001]; the delayed bleeding rate in the VPZ group was significantly lower than that in the lansoprazole subgroup [RR=0.47, 95%CI (0.25, 0.90), Z=2.28, P=0.02]. In the treatment of PU, the incidence of adverse events with VPZ was significantly higher than that with PPI in the duodenal ulcer subgroup [RR=1.13, 95%CI (1.02, 1.26), Z=2.38, P=0.017]. CONCLUSIONS For post-ESD ulcers, VPZ demonstrates superior therapeutic efficacy compared to PPI and can reduce ulcer recurrence rates in patients with a history of PU. However, it does not offer advantages in terms of safety for duodenal ulcer treatment.
7.Intervention of Exercise Combined with Shenghui Tang in M1AChR Regulation of Mitochondrial Autophagy Improves Learning and Memory Ability of Alzheimer's Disease Model Rats
Xiaoxue TAO ; Min XIAO ; Kunyang TANG ; Bo WANG ; Chunchun ZHAO ; Rongxiang LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):120-130
ObjectiveTo make clear exercise combined with Shenghui Tang interferes in acetylcholine receptor (M1AChR) to improve mitochondrial autophagy and enhance cognition of Alzheimer's disease (AD) model rats through the adenylate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsForty-eight male SD rats of SPF grade were randomly divided into a blank group, a model group, a Shenghui Tang group (9.3 g·kg-1), an exercise group, an exercise + Shenghui Tang group (9.3 g·kg-1), and a rapamycin group (1.5 mg·kg-1). Except for the blank group, the rat model of AD was constructed by injecting amyloid beta (Aβ1-42) into hippocampus stereotaxically. The exercise group received treadmill exercise for 4 weeks, while the Shenghui Tang group received intragastric administration for 4 weeks, and the exercise + Shenghui Tang group received treadmill exercise and intragastric administration of Shenghui Tang for 4 weeks simultaneously. After the intervention, the Morris water maze test was used to detect the learning and memory ability. Spontaneous behavior was observed in the open field test. The pathological structure of hippocampal neurons was observed by NISSl staining. The expression level of M1AChR in hippocampus was detected by immunohistochemistry (IHC). The autophagy ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The apoptosis rate was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of Beclin1 and microtubule-associated protein light chain 3β (LC3β) was detected by immunofluorescence (IF). The protein expression of M1AChR, AMPK, p-AMPK, mTOR, Beclin1, LC3β, and chelate 1 (SQSTM1/p62) in hippocampus was detected by Western blot. ResultsCompared with the blank group, the model group exhibited significantly increased platform escape latency on the fifth day (P<0.01) and significantly decreased activity distance in the target quadrant and times of crossing the platform (P<0.01). The total movement distance in the open field, the time of movement in the central area, and the average speed obviously decreased (P<0.05). The arrangement of nerve cells in hippocampus CA1 region was dispersed, and the numbers of Nissl bodies and M1AChR positive cells significantly decreased (P<0.01). The expression of TUNEL positive cells was significantly increased (P<0.01). The typical autophagic lysosomal structure decreased. The protein expression of M1AChR, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, LC3Ⅱ/Ⅰ in hippocampus was significantly decreased (P<0.01), and the protein expression of p62 was significantly increased (P<0.01). Compared with the model group, the exercise + Shenghui Tang group exhibited obviously improved space exploration and positioning navigation ability (P<0.05, P<0.01). The total movement distance in the open field, the time of movement in the central area, and the average speed of movement significantly increased (P<0.01). The number of Nissl bodies significantly increased (P<0.01). The number of M1AChR positive cells in hippocampus was significantly increased (P<0.01). The expression of TUNEL positive cells was significantly decreased (P<0.01). The protein expression of M1AChR, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, LC3Ⅱ/Ⅰ in hippocampus was significantly increased (P<0.01), while the protein expression of p62 was significantly decreased (P<0.01). Compared with the exercise + Shenghui Tang group, the Shenghui Tang group and the exercise group showed significantly increased platform escape latency on the fifth day (P<0.01) and obviously decreased activity distance in the target quadrant and times of crossing the platform (P<0.05, P<0.01). The total movement distance in the open field, the time of movement in the central area, and the average speed of movement significantly decreased (P<0.01). The number of Nissl bodies and the number of M1AChR positive cells significantly decreased (P<0.01). The expression of TUNEL positive cells was obviously increased (P<0.05). Ultrastructure of the hippocampal region showed decreased autophagy level. The protein expression of M1AChR, p-AMPK/AMPK, p-mTOR/mTOR, LC3Ⅱ/Ⅰ in the hippocampus was obviously decreased in the Shenghui Tang group (P<0.05, P<0.01), while the protein expression of p62 was significantly increased (P<0.01). In the exercise group, the protein expression of M1AChR, p-AMPK/AMPK, Beclin1, and LC3Ⅱ/Ⅰ was obviously decreased (P<0.05, P<0.01), while the protein expression of p-mTOR/mTOR and p62 was significantly increased (P<0.01). ConclusionExercise combined with traditional Chinese medicine can enhance the expression of M1AChR in the hippocampus of AD model rats, induce autophagy through the AMPK/mTOR signaling pathway, and improve the learning and memory ability of AD rats.
8.Mechanisms of Tianma Goutengyin in Alleviating Neuronal Injury in Vascular Dementia Model Rats by Inhibiting A1 Astrocyte Activation via Regulating TNF-α/STAT3/α1ACT Signaling Pathway
Xiaoyan WANG ; Min ZHAO ; Feng TIAN ; Min XIAO ; Nan QU ; Fugui LIU ; Chixiao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):56-65
ObjectiveTo investigate the effects of Tianma Goutengyin on the tumor necrosis factor-α (TNF-α)/signal transducer and activator of transcription 3 (STAT3)/α1-antichymotrypsin C-terminal tail fragment (α1ACT) signaling pathway and A1-type astrocytes in a rat model of vascular dementia. MethodsSeventy-two male Sprague-Dawley rats were randomly divided into six groups (n=12 per group): Sham-operated group, model group, Tianma Goutengyin high-, medium-, and low-dose groups (5.13, 10.26, and 20.52 g·kg-1), and a nimodipine group (8.1 mg·kg-1). The vascular dementia model was established by permanent bilateral common carotid artery occlusion, followed by 4 weeks of intervention. Learning and memory ability were evaluated using the novel object recognition test, and behavioral performance was assessed using the forced swimming test. Levels of interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2) in hippocampal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Hippocampal neuronal morphology was observed by Nissl staining, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Immunohistochemistry was used to detect positive expression of brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). Western blot analysis was performed to measure the protein expression levels of TNF-α, TNF receptor 1 (TNFR1), phosphorylated STAT3 (p-STAT3), α1ACT, IL-6, complement component 3 (C3), BDNF, S100 calcium-binding protein A10 (S100A10), and GFAP in hippocampal tissue. ResultsCompared with the sham-operated group, the model group showed a significantly reduced relative recognition index in the novel object recognition test (P<0.01), prolonged immobility time and increased immobility frequency in the forced swimming test (P<0.01). Hippocampal IL-6 and CCL2 levels were significantly increased (P<0.01). Nissl staining revealed a marked reduction in neuronal number and loss of Nissl bodies (P<0.01). MBP-positive expression was significantly decreased (P<0.01), apoptosis was significantly increased (P<0.01), BDNF-positive expression was significantly reduced (P<0.05), and GFAP-positive expression was significantly increased (P<0.01). In addition, the protein expression levels of TNF-α, TNFR1, p-STAT3, α1ACT, IL-6, and C3 were significantly elevated (P<0.01), while BDNF and S100A10 expression levels were significantly decreased (P<0.01). Compared with the model group, all Tianma Gouteng yin dose groups exhibited a significant increase in the relative recognition index (P<0.05), shortened immobility time and reduced immobility frequency (P<0.05, P<0.01). IL-6 and CCL2 levels were significantly decreased (P<0.01), neuronal number was significantly increased (P<0.05, P<0.01), and MBP-positive expression was significantly enhanced (P<0.01). Apoptosis was significantly reduced (P<0.01), BDNF-positive expression was significantly increased (P<0.05), and GFAP-positive expression was significantly decreased (P<0.01). Moreover, the protein expression levels of TNF-α, TNFR1, p-STAT3, α1ACT, IL-6, and C3 were significantly decreased (P<0.01), while BDNF and S100A10 protein expression levels were significantly increased (P<0.01). ConclusionTianma Goutengyin may inhibit A1-type astrocyte activation in rats with vascular dementia through the TNF-α/STAT3/α1ACT signaling pathway, thereby reducing neuronal apoptosis and improving learning and memory function.
9.Epidemiologic Burden of Colorectal Cancer in Xishan District, Kunming City, Yunnan Province, 2018—2020
Mingzhu GAO ; Ruiqi CAI ; Sile LI ; Yuying PANG ; Yanyan YANG ; Weilin ZHANG ; Min ZHAO
Cancer Research on Prevention and Treatment 2026;53(2):142-151
Objective To analyze the epidemiologic burden of colorectal cancer in Xishan District, Kunming City, Yunnan Province from 2018 to 2020. Methods Indicators of epidemiologic burden were calculated, including incidence rate, mortality rate, age-specific incidence/mortality rates, potential years of life lost (PYLL), and disability-adjusted life years (DALY) based on the National Disease Control and Prevention Center’s "Cancer Information Registration and Reporting System" and "Cause of Death Registration System". Results From 2018 to 2020, the ASR (China) for the incidence of colorectal cancer in Xishan District, Kunming City increased from 25.27/105 to 26.29/105, while the ASR (China) for mortality decreased from 17.11/105 to 16.03/105. The PYLL in 2018–2020 were
10.Mechanisms of Mahuang Lianqiao Chixiaodoutang in Improving Obesity-type Polycystic Ovary Syndrome in Rats Based on PI3K/Akt Signaling Pathway
Shiwei HU ; Biran ZHU ; Jinrong ZHANG ; Luyao RUAN ; Ji KUANG ; Jianghuan HUA ; Zhe LIU ; Yanyue YAO ; Ji WANG ; Min ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):21-31
ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang (MLC) improves obesity-type polycystic ovary syndrome (PCOS) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsThirty-six female Sprague-Dawley (SD) rats were randomly divided into a blank control group (Con) and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole (1 mg·kg-1) combined with a high-fat diet (HFD). After model establishment, the obesity-type PCOS model preparation group was further divided into the model group (Mod, normal saline), metformin group (Met, 0.3 g·kg-1), low-dose MLC group (MLC-L, 4.3 g·kg-1), medium-dose MLC group (MLC-M, 8.6 g·kg-1), and high-dose MLC group (MLC-H, 17.2 g·kg-1). Active components of MLC and targets of obesity-type PCOS were screened from databases, a protein-protein interaction (PPI) network was constructed, and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin (HE) staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), testosterone (T), and estradiol (E2). Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K (p-PI3K/PI3K), phosphorylated Akt/Akt (p-Akt/Akt), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing, the abundances of Lachnospiraceae, Lachnoclostridium, and Dorea were increased in the MLC groups (P<0.05), while the abundance of Veillonella was decreased (P<0.05). KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that, compared with the Mod group, body weight decreased to normal levels in the Met, MLC-M, and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T, FSH, and LH/FSH were reduced (P<0.05, P<0.01), while the E2 level was increased (P<0.01). Ovarian cell apoptosis was reduced (P<0.01), and the protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and Bcl-2 in ovarian tissue were significantly increased, whereas Bax protein expression was significantly decreased (P<0.05, P<0.01). ConclusionMLC can regulate gut microbiota structure, effectively improve ovarian pathology in rats with obesity-type PCOS, and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.


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