1.Mechanism of Shenfu Xiongze Prescription in Regulating Autophagy Level to Intervene in Myocardial Remodeling in Rats via AMPK/mTOR Signaling Pathway
Xueqing WANG ; Wei ZHONG ; Liangliang PAN ; Caihong LI ; Man HAN ; Xiaowei YANG ; Yuanwang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):136-144
ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline (ISO) was established. Rats were divided into the blank group,the model group,the low-,medium-, and high-dose groups of Shenfu Xiongze prescription,and the captopril group, 6 rats in each group. Except for the blank group,the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg-1 ISO for 3 consecutive weeks. At the same time of modeling, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution (8.4,16.8,and 33.6 g·kg-1),and the captopril group was administered captopril solution (25 mg·kg-1). As for the blank group and the model group, the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function,and the heart weight index was detected. Masson staining and hematoxylin-eosin (HE) staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 (IL-6) and B-type natriuretic peptide (BNP) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of type Ⅰ collagen (Collagen Ⅰ),type Ⅲ collagen (Collagen Ⅲ),and microtubule-associated protein 1 light chain 3 (LC3) proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ,Collagen Ⅲ,α-smooth muscle actin (α-SMA),LC3,yeast Atg6 homolog protein (Beclin-1),AMPK,and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction (real-time PCR). The protein expression of Collagen Ⅰ,α-SMA,transforming growth factor-β1 (TGF-β1),LC3,Beclin-1,p62, phosphorylation(p)-AMPK,p-mTOR,AMPK,and mTOR was detected by Western blot. ResultsCompared with the normal group,rats in the model group exhibited significantly decreased values of ejection fraction (EF) and left ventricular fractional shortening (FS) (P<0.01), significantly increased values of left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs) (P<0.01). Additionally, the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue, significantly elevated levels of serum IL-6 and BNP (P<0.01), significantly increased mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,and mTOR (P<0.01),and markedly decreased mRNA and protein levels of LC3,Beclin-1,and AMPK (P<0.05,P<0.01). Compared with the model group, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values (P<0.01) and lowered LVIDd and LVIDs (P<0.05). In these groups, the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP (P<0.01), significantly reduced protein expression of Collagen Ⅰ, α-SMA, TGF-β1, p62, and p-mTOR (P<0.01), significantly decreased mRNA expression of Collagen Ⅰ, Collagen Ⅲ, α-SMA, and mTOR (P<0.01), and significantly increased mRNA and protein levels of LC3, Beclin-1, and AMPK (P<0.05,P<0.01). ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level,enhance cardiac function,and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.
2.Joint Relation Extraction of Famous Medical Cases with CasRel Model Combining Entity Mapping and Data Augmentation
Yuxin LI ; Xinghua XIANG ; Hang YANG ; Dasheng LIU ; Jiaheng WANG ; Zhiwei ZHAO ; Jiaxu HAN ; Mengjie WU ; Qianzi CHE ; Wei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):218-225
ObjectiveTo address the challenges of unstructured classical Chinese expressions, nested entity relationships, and limited annotated data in famous traditional Chinese medicine(TCM) case records, this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping, aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction(CasRel) model for TCM semantics was designed, integrating a pre-trained bidirectional encoder representations from transformers(BERT) layer for classical TCM texts to enhance semantic representation, and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model, combining data augmentation and entity mapping, outperformed the pipeline-based Bert-Radical-Lexicon(BRL)-bidirectional long short-term memory(BiLSTM)-Attention model. The overall precision, recall, and F1-score across 12 relation types reached 65.73%, 64.03%, and 64.87%, which represent improvements of 14.26%, 7.98%, and 11.21% compared to the BRL-BiLSTM-Attention model, respectively. Notably, the F1-score for tongue syndrome relations increased by 22.68%(69.32%), and the prescription-syndrome relations performed the best with the F1-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts, offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation, prescription optimization, and drug compatibility, providing a methodological reference for TCM artificial intelligence research.
3.Effect of Qingfei Shenshi Decoction (清肺渗湿汤) Combined with Western Medicine on Clinical Effectiveness and Immune Function for Patients with Bronchial Asthma of Heat Wheezing Syndrome
Ying SUN ; Haibo HU ; Na LIU ; Fengchan WANG ; Jinbao ZONG ; Ping HAN ; Peng LI ; Guojing ZHAO ; Haoran WANG ; Xuechao LU
Journal of Traditional Chinese Medicine 2026;67(1):38-44
ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction (清肺渗湿汤) combined with western medicine for patients with bronchial asthma of heat wheezing syndrome, and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group, each group with 43 participants. The control group received conventional western medicine, and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group, 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness; secondary outcome measures included traditional Chinese medicine (TCM) syndrome score, asthma control test (ACT) score, pulmonary function indices such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), serum inflammatory factor levels including interleukin-4 (IL-4), tumour necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP), and immune function indices including CD3+, CD4+, CD8+, CD4+/CD8+. All outcome measures were evaluated before and after treatment. Vital signs were monitored, and electrocardiography, blood routine, urine routine, liver function, and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% (39/40), which was significantly higher than that of the control group (85.0%, 34/40, P<0.05). After treatment, both groups showed decreased TCM syndrome scores, IL-4, TNF-α, hs-CRP, and CD8+ levels, as well as increased ACT scores, CD3+, CD4+, CD4+/CD8+, FEV1, FVC, and PEF levels (P<0.05 or P<0.01). Moreover, the improvements in these indices were more significant in the treatment group than in the control group (P<0.05 or P<0.01). No significant abnormalities in safety indicators were observed in either group, and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms, pulmonary function, and clinical effectiveness, with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.
4.Expert consensus on clinical application of parenteral direct thrombin inhibitors in perioperative period
Mingyu JIANG ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Fengjiao KANG ; Anhua WEI ; Danjie ZHAO ; Lin WANG ; Ying SHAO ; Li TANG ; Yi WANG ; Shuhong LIANG ; Huijuan LIU ; Guirong XIAO ; Yue LI
China Pharmacy 2026;37(6):689-699
OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors (DTIs) in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (the Affiliated Hospital of UESTC), a multidisciplinary working group was established. Through literature review and the Delphi method, clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework; systematic searches were conducted in CNKI, Medline, Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations (each with an expert consensus rate exceeding 90%) on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection, dosing ranges, key monitoring points, and safety management strategies for parenteral DTIs in various scenarios, including the perioperative period of ventricular assist device implantation, the perioperative period of cardiac surgery, perioperative patients with lower-extremity atherosclerotic disease, the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome, the perioperative period of carotid artery stenting in patients with carotid stenosis, the perioperative period of patients with right heart thrombosis, and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition, warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus, which is formulated based on the best available evidence, provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.
5.Current quality status and management countermeasures of occupational health technical services in Zhejiang Province
Qiuliang XU ; Feng HAN ; Peng WANG ; Zhen ZHOU ; Fei LI ; Hongwei XIE ; Yong HU ; Weiming YUAN ; Lifang ZHOU ; Hua ZOU
Journal of Environmental and Occupational Medicine 2026;43(3):341-346
Background The quality of occupational health technical services is directly linked to the protection of workers' health rights and the efficacy of occupational disease prevention and control. However, the industry still faces critical challenges: sporadic instances of institutional non-compliance and persistent irregularities in professional practice continue to undermine overall service performance. Objective To assess the current quality status of occupational health technical services in Zhejiang Province and propose countermeasures for quality improvement, providing a scientific basis for policy optimization and service delivery quality enhancement. Methods A total of 69 occupational health technical service institutions in Zhejiang Province that obtained formal accreditation as of April 30, 2024, were sampled, including 3 public institutions and 66 private institutions (comprising 3 formerly Class-A, 28 formerly Class-B, 11 formerly Class-C, and 24 newly certified institutions). Following the Technical Protocol for Quality Monitoring of Occupational Health Technical Service in Zhejiang Province and the Technical Protocol for Proficiency Testing of Occupational Health Detection in Zhejiang Province, a quality assessment task force comprising national and provincial experts was established. Evaluation was conducted across four dimensions: qualification maintenance and compliance, standardization of technical services, authenticity of technical services, and proficiency testing, utilizing a combination of document review, on-site inspections, and technical skill assessments. Results The occupational health technical service institutions in Zhejiang Province were predominantly private entities (82.5%), with significant disparities in overall service quality. The pass rates for qualification maintenance and compliance, technical service standardization, technical service authenticity, and the excellence rate for laboratory proficiency testing were 81.5%, 80.7%, 97.3%, and 90.4%, respectively. Regarding qualification maintenance, the pass rates for "environmental conditions" (49.8%, 56.7%) and "instrumentation and equipment" (58.2%、65.6%) were significantly lower for formerly Class-C and newly certified institutions compared to other categories. In terms of technical standardization, "standardized on-site inspections" recorded the lowest pass rate (67.4%), with newly certified institutions at only 48.0%. Regarding technical service authenticity, formerly Class-C institutions exhibited issues such as missing raw chromatograms for blank samples (85.7% pass rate). In laboratory proficiency testing, public and formerly Class-A institutions achieved 100% excellence rates, but the performance of formerly Class-C and newly certified institutions was comparatively weak; specifically, the failure rate for organic analysis in formerly Class-C institutions reached 20%; the failure rate for dust testing items in newly certified institutions was 10.3%. Conclusion The overall quality of occupational health technical services in Zhejiang Province still requires significant improvement, particularly in basic institutional conditions, the standardization of on-site inspections, and laboratory proficiency in organic and dust analysis. Formerly Class-C and newly certified institutions should be the primary focus of quality management efforts. Differentiated regulatory strategies are recommended, alongside strengthening interim and ex-post supervision to gradually enhance the quality of occupational health technical services across all institutions.
6.Comparison of anti-VEGF treatment at different preoperative time points on retinal neovascularization in PDR
Ruolan LING ; Xi WANG ; Yue HAN ; Yawen QIN ; Jie ZHONG ; Jie LI
International Eye Science 2026;26(5):856-861
AIM:To evaluate the optimal timing of preoperative intravitreal anti vascular endothelial growth factor(VEGF)therapy in proliferative diabetic retinopathy(PDR)using intraoperative fluorescein angiography(IOFA).METHODS:A retrospective case series study was conducted on patients who underwent vitrectomy for PDR with vitreous hemorrhage(VH)at Sichuan Provincial People's Hospital from January 2023 to February 2025. Patients were divided into three groups according to the interval between intravitreal conbercept injection and surgery: Group A(3 d before surgery), Group B(7 d before surgery), and Group C(14 d before surgery). IOFA was used to assess the number and size of retinal neovascularization(NV). Additional data were collected including preoperative best corrected visual acuity(BCVA), vitreous hemorrhage grading, operative time, frequency of intraoperative endodiathermy, duration of high perfusion pressure, vitreoretinal adhesion grade, postoperative BCVA, and central macular thickness(CMT). Multidimensional analyses were performed.RESULTS:This study enrolled a total of 91 patients(94 eyes)with PDR accompanied by vitreous hemorrhage. Among them, Group A consisted of 31 patients(31 eyes; 18 males, 13 females; mean age 53.26±12.38 y), Group B consisted of 34 patients(37 eyes; 21 males, 13 females; mean age 51.61±14.16 y), and Group C consisted of 26 patients(26 eyes; 18 males, 8 females; mean age 51.00±12.02 y), with baseline characteristics comparable among the three groups(all P>0.05). Comparative analysis of NV visualized via IOFA revealed that both the number and size of NVs were significantly lower in Groups B and C than in Group A(all P<0.0167), while no statistically significant differences were observed between Groups B and C(both P>0.05). No significant differences were found among the three groups regarding other intraoperative parameters, including operation time, frequency of electrocoagulation application, duration of high perfusion pressure, or grading of vitreoretinal adhesion(all P>0.05).CONCLUSION:IOFA confirms that preoperative anti-VEGF therapy administered 7 or 14 d before surgery is more effective than a 3 d interval in suppressing retinal NV activity in PDR patients.
7.Genetic disease diagnosis and treatment in Shanghai: Survey and countermeasures for clinical genetics specialist training.
Xiaoju HUANG ; Lin HAN ; Li CAO ; Taosheng HUANG ; Duan MA ; Jian WANG ; Wenjuan QIU ; Fanyi ZENG ; Luming SUN ; Chenming XU ; Songchang CHEN ; Xinyu KUANG ; Hong TIAN
Chinese Journal of Medical Genetics 2026;43(4):241-247
OBJECTIVE:
To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists.
METHODS:
By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements.
RESULTS:
The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development.
CONCLUSION
Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans
;
China
;
Surveys and Questionnaires
;
Genetic Diseases, Inborn/genetics*
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Cross-Sectional Studies
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Genetics, Medical/education*
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Genetic Testing
8.Mechanisms of Huanglian Jiedutang and Its Major Active Constituents in Inhibiting LPS-induced M1 Polarisation of BV2 Microglia
Haojia ZHANG ; Kai WANG ; Kunjing LIU ; Xin LAN ; Zijin SUN ; Chunyu WANG ; Wenyuan MA ; Wei SHAO ; Jinhua HAN ; Liyang DONG ; Changxiang LI ; Xueqian WANG ; Youxiang CUI ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):44-55
ObjectiveTo investigate whether Huanglian Jiedutang (HLJD) and its major active constituents (geniposide, baicalin, and berberine) can inhibit the inflammatory response of BV2 cells under lipopolysaccharide (LPS) stimulation via the high-mobility group protein B1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, and to explore differences in therapeutic efficacy among the three monomers, their combined formula, and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 (CCK-8) method to examine the effects of different concentrations of dimethyl sulfoxide (DMSO, 0.8%, 0.4%, 0.2%, 0.1%, and 0.05%) on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD (200, 100, 50, 25, 12.5, 6.25 mg·L-1). Nitric oxide (NO) assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography (HPLC) determined the content of geniposide, baicalin, and berberine in HLJD, and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay (ELISA) measured levels of inflammatory factors (TNF-α, IL-1β, IL-6, IL-10) in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1, TLR4, and NF-κB-related proteins. ResultsCompared with the blank group, DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L-1 HLJD. Under stimulation with 2 mg·L-1 LPS, this concentration of HLJD effectively reduced NO release, and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide, 15 μg of baicalin, and 30 μg of berberine. Based on these ratios, experimental groups were blank, LPS (2 mg·L-1), HLJD (200 mg·L-1), monomer combination, geniposide (4.8 mg·L-1), baicalin (3 mg·L-1), and berberine (6 mg·L-1). The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α, IL-1β, IL-6, and IL-10 in the supernatant (P<0.01). HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01) while upregulating anti-inflammatory IL-10 (P<0.01), with the monomer combination showing the strongest effect (P<0.05, P<0.01). Compared with the blank group, LPS significantly increased the proportion of CD80⁺CD86⁺ (M1-type) BV2 cells (P<0.01). HLJD and its constituents partially inhibited M1 polarization (P<0.05, P<0.01), with the monomer combination exhibiting the most pronounced effect (P<0.05, P<0.01). Compared with the blank group, LPS upregulated HMGB1, TLR4, and NF-κB-related proteins (P<0.01), whereas HLJD and its active constituents significantly reduced their expression (P<0.05, P<0.01), with the monomer combination having the strongest regulatory effect (P<0.05, P<0.01). ConclusionHLJD and its major active constituents (geniposide, baicalin, berberine) can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect, significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.
9.The Role and Regulatory Mechanisms of FOXO1 in Hepatic Lipid Deposition
Meng JIA ; Fang-Hui LI ; Shi-Zhan YAN ; Ai-Ju LI ; Yi-Le WANG ; Pin-Shi NI ; Jia-Han HE ; Yin-Lu LI
Progress in Biochemistry and Biophysics 2026;53(4):905-919
Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.
10.WANG Qingguo's Experience in Treatment of Headache Based on the Concept of "Achieving Harmony by Unblocking and Balancing"
Chuxin ZHANG ; Zilin REN ; Yang ZHAO ; Jinhua HAN ; Bomin ZHANG ; Fafeng CHENG ; Changxiang LI ; Xueqian WANG ;
Journal of Traditional Chinese Medicine 2026;67(9):935-940
This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment", clinical presentations often involve a complex mixture of deficiency and excess, as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing", advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals, treatment should focus on dispersing and unblocking through modified Gegen Decoction (葛根汤). For wind-dampness binding, it is recommended to unblock and drain, using modified Qingshang Juantong Decoction (清上蠲痛汤). For damp-heat congestion, unblocking and clearing is the method, using modified Toufeng Shen Formula (头风神方). For liver-gallbladder qi constraint, unblocking and soothing is the treatment principle, and modified Sanpian Decoction (散偏汤) is suggested. For insufficiency of center qi, even supplementation method is recommended, and modified Yiqi Congming Decoction (益气聪明汤) can be used. For liver yang hyperactivity, unblocking and subduing are combined, using modified Xunlong Decoction (驯龙汤). For deficiency-cold in the liver and stomach, warming, harmonizing, unblocking, and descending are applied, using modified Wuzhuyu Decoction (吴茱萸汤). For blood deficiency with cold congelation, unblocking and nourishing are undertaken together, using modified Danggui Sini Decoction (当归四逆汤). The ultimate goal is to restore the dynamic balance of yin, yang, qi, and blood in the body, thereby allevia-ting pain by restoring clarity and function to the head orifices.

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