Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

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, S_max) alternated with one minute at low speed (50%-55% S_max), 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.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive. OBJECTIVE: This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD. SEARCH STRATEGY: Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025. INCLUSION CRITERIA: Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included. DATA EXTRACTION AND ANALYSIS: Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. RESULTS: A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = -0.57; 95% confidence interval [CI] = [-0.87, -0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = -1.00; 95% CI = [-1.18, -0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = -0.38; 95% CI = [-0.61, -0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture's relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect. CONCLUSION Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future. Please cite this article as: Kuang HJ, Yang HS, Feng YX, Tang H, Fan Q, Xu YQ, Cui S, Musil R, Luxenburger H, Zhang YX, Zhao H, Zhang YQ. Efficacy and safety of acupuncture therapies for adult patients with mild and moderate major depressive disorder: A systematic review and meta-analysis. J Integr Med. 2025; 23(5):471-491.
Humans ; Acupuncture Therapy/methods* ; Depressive Disorder, Major/therapy* ; Adult ; Antidepressive Agents/therapeutic use* ; Treatment Outcome ; Randomized Controlled Trials as Topic

To review the clinical characteristics, short-term outcomes, and risk factors of patients with infective endocarditis(IE) who underwent surgical treatment at a single center, and to summarize treatment experience.

INTRODUCTION: Adolescent depression is prevalent, and teen suicide rates are on the rise locally. A systemic review to understand associated risk and protective factors is important to strengthen measures for the prevention and early detection of adolescent depression and suicide in Singapore. This systematic review aims to identify the factors associated with adolescent depression in Singapore. METHODS: A systematic search on the following databases was performed on 21 May 2020: PubMed, EMBASE and PsycINFO. Full texts were reviewed for eligibility, and the included studies were appraised for quality using the Newcastle Ottawa Scale. Narrative synthesis of the finalised articles was performed through thematic analysis. RESULTS: In total, eight studies were included in this review. The four factors associated with adolescent depression identified were: (1) sociodemographic factors (gender, ethnicity); (2) psychological factors, including childhood maltreatment exposure and psychological constructs (hope, optimism); (3) coexisting chronic medical conditions (asthma); and (4) lifestyle factors (sleep inadequacy, excessive internet use and pathological gaming). CONCLUSION The identified factors were largely similar to those reported in the global literature, except for sleep inadequacy along with conspicuously absent factors such as academic stress and strict parenting, which should prompt further research in these areas. Further research should focus on current and prospective interventions to improve mental health literacy, targeting sleep duration, internet use and gaming, and mitigating the risk of depression in patients with chronic disease in the primary care and community setting.
Humans ; Singapore/epidemiology* ; Adolescent ; Risk Factors ; Depression/etiology* ; Protective Factors ; Male ; Female ; Life Style ; Suicide

OBJECTIVE: To investigate the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on cognitive function and insulin resistance in patients with type 2 diabetes mellitus (T2DM) and cognitive decline. METHODS: Ninety patients with T2DM and cognitive decline were randomly divided into a moxibustion group (n=45, 3 cases dropped out, 2 cases were eliminated) and a waiting moxibustion group (n=45, 2 cases dropped out). Both groups received routine hypoglycemic treatment for 12 weeks. The moxibustion group additionally received Huayu Tongluo moxibustion at Baihui (GV20), Shenting (GV24), and Dazhui (GV14). Pressing moxibustion was applied to Baihui (GV20) for 20 min, while suspended moxibustion was applied to Shenting (GV24) and Dazhui (GV14) for 20 min each. Treatments of moxibustion were administered every other day (three times per week) for 12 weeks. All patients were followed up for 12 weeks, during which their original hypoglycemic medication regimen was maintained. Before treatment, after 12 weeks of treatment, and at the 12-week follow-up, the scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Addenbrooke's cognitive examination Ⅲ (ACE-Ⅲ), symbol digit modalities test (SDMT), and Athens insomnia scale (AIS) and the insulin resistance index (HOMA-IR) were observed in the two groups. RESULTS: Compared with before treatment, the MoCA scores, MMSE scores, ACE-Ⅲ subscale scores (attention, memory, language fluency, language, visuospatial ability) and total scores, and SDMT scores were increased (P<0.01), while the AIS scores were decreased (P<0.05) in the moxibustion group after treatment and at follow-up. Compared with before treatment, the MMSE score, ACE-Ⅲ subscale scores (memory, attention) and total score after treatment, as well as the ACE-Ⅲ subscale scores (language, memory, attention) and total score, and SDMT score at follow-up were increased (P<0.05, P<0.01) in the waiting moxibustion group. Compared with before treatment, HOMA-IR was decreased in both groups after treatment and at follow-up (P<0.01). At follow-up, ACE-Ⅲ subscale scores (attention, memory), and the total score in the moxibustion group were lower than those after treatment (P<0.05, P<0.01), and the ACE-Ⅲ language subscale score, total ACE-Ⅲ score, and SDMT score in the waiting moxibustion group were higher than those after treatment (P<0.01, P<0.05). After treatment and at follow-up, compared with the waiting moxibustion group, the moxibustion group had higher MoCA scores, MMSE scores, SDMT scores, ACE-Ⅲ subscale scores (attention, memory, language fluency) and total scores (P<0.05, P<0.01), and lower HOMA-IR (P<0.05). CONCLUSION Huayu Tongluo moxibustion can effectively improve cognitive function in patients with T2DM and cognitive decline. This improvement may be associated with the reduction in insulin resistance.
Humans ; Insulin Resistance ; Diabetes Mellitus, Type 2/complications* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognition ; Acupuncture Points ; Adult ; Cognitive Dysfunction/therapy*