OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

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*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To observe the clinical effect and safety of edaravone and dexborneol concentrated solution for injection combined with rosuvastatin calcium capsules in the treatment of patients with acute posterior circulation cerebral infarction.Methods Patients with acute posterior circulation cerebral infarction were divided into control group and treatment group according to cohort method.The control group was treated with rosuvastatin calcium 5 mg,while the treatment group was treated with intravenous drip of edaravone and dexborneol concentrated solution for injection 15 mL on the basis of control group.The clinical effect,neurological function,biochemical indicators,oxidative stress response indicators,the levels of Toll like receptor 4/nuclear factor κB(TLR4/NF-κB)signaling pathway molecules,prognosis,and adverse drug reactions were compared between the two groups.Results There were 49 cases in control group and 51 cases in treatment group.After treatment,the total effective rates in treatment group and control group were 92.16％(47 cases/51 cases)and 77.55％(38 cases/49 cases),with statistically significant difference(P＜0.05).After treatment,the levels of neuron specific enolase in treatment group and control group were(11.67±1.35)and(16.77±1.94)μg·L-1;the levels of central nervous system-specific protein were(1.01±0.12)and(1.54±0.16)μg·L-1;the levels of low density lipoprotein cholesterol were(2.03±0.24)and(3.74±0.38)mmol·L-1;the levels of triglyceride were(1.28±0.14)and(2.12±0.23)mmol·L-1;the levels of total cholesterol were(3.11±0.32)and(4.15±0.42)mmol·L-1;the levels of creatine kinase isozyme were(8.76±1.02)and(10.12±1.06)U·L-1;the levels of high-sensitivity C-reactive protein were(11.01±1.25)and(15.32±1.64)mg·L-1;the levels of serum reactive oxygen species were(387.68±39.24)and(473.11±48.23)μmol·L-1;the levels of malondialdehyde were(3.02±0.39)and(4.14±0.45)nmol·mL-1;the levels of superoxide dismutase were(59.24±6.05)and(41.67±4.97)U·mL-1;the relative expression levels of TLR4 mRNA were 0.26±0.03 and 0.43±0.04;the relative expression levels of NF-KB mRNA were 0.17±0.02 and 0.25±0.03;the modified Rankin scale scores were 2.02±0.29 and 2.94±0.30;the activity of daily living scores were 56.34±5.74 and 45.64±4.69.The above indexes were significantly different between control group and treatment group(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 31.37％and 26.53％,with no statistically significant difference between the two groups(P＞0.05).Conclusion Edaravone and dexborneol concentrated solution for injection combined with rosuvastatin calcium capsules is effective in the treatment of patients with acute posterior circulation cerebral infarction,and can effectively regulate the patients'neurological function,oxidative stress response,blood lipid levels and TLR4/NF-κB signaling pathway molecules,and significantly improve the prognosis.

Objective To observe the application effect of montelukast sodium combined with terbutaline on cough variant asthma(CVA)in children and its influence on airway remodeling and peripheral blood inflammatory indicators.Methods The children with CVA were randomly classified into control group and treatment group.The control group was given aerosol inhalation of terbutaline(5 mg each time,twice a day),and on the basis of the control group,the treatment group was combined with oral administration of montelukast sodium granules(4 mg each time,once a day,taking before going to bed),and both groups were continuously treated for 3 months.The clinical efficacy,airway cross-section area(AO),airway lumen area(AI),airway wall thickness(T),airway wall area(WA),serum interleukin-5(IL-5),eosinophilic chemotactic factor(Eotaxin),macrophage inflammatory protein-1α(MIP-1α)and T lymphocyte subgroups CD4+,CD8+and CD4+/CD8+were compared between the two groups of children,and the medication safety was assessed.Results Fifty-three cases in control group and 53 cases in treatment group were included.After treatment,the total effective rates in treatment group and control group were 96.23％(51 cases/53 cases)and 83.02％(44 cases/53 cases),respectively(P＜0.05).The AO values in treatment group and control group were(39.42±3.67)and(45.69±4.92)mm2;AI values were(22.36±2.85)and(27.06±3.18)mm2;T values were(1.12±0.28)and(1.44±0.33)mm;WA values were(53.82±4.17)and(60.13±4.66)mm2;serum IL-5 levels were(25.46±5.83)and(41.46±7.64)ng·L-1;Eotaxin levels were(181.24±30.05)and(238.21±39.42)ng·L-1;MIP-1a levels were(15.24±3.67)and(22.43±4.05)ng·L-1;CD4+levels were(37.18±4.06)％and(33.57±3.82)％;CD8+levels were(24.08±3.15)％and(27.31±3.07)％;and CD4+/CD8+levels were 1.54±0.33 and 1.24±0.28,respectively(all P＜0.05).The total incidences of adverse drug reactions in treatment group and control group were 9.43％(5 cases/53 cases)and 3.77％(2 cases/53 cases),respectively(P＞0.05).Conclusion Montelukast sodium combined with terbutaline has an exact efficacy in the treatment of CVA in children,and it can effectively reverse airway remodeling,reduce inflammation level and enhance immune function,and it has good safety.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Objective To assess the effect of ultrasonic thyroid artificial intelligence(AI)-assisted diagnostic system(AI-assisted diagnostic system)for diagnosing medullary thyroid carcinoma(MTC)compared with different physicians and taken papillary thyroid carcinoma(PTC)as the controls.Methods Totally 63 MTC,70 PTC and 62 benign thyroid nodules confirmed by pathology were enrolled.AI-assisted diagnostic system was utilized to analyze thyroid nodules and identify the likelihood of malignancy,and the probability value threshold was set at ≥0.40.All thyroid nodules were retrospectively reviewed and categorized by 3 physicians(1 senior physician,1 attending physician and 1 junior physician)according to Chinese thyroid imaging reporting and data system(C-TIRADS).The efficacy of AI-assisted diagnostic system and physicians for diagnosing MTC and PTC were evaluated.Results AI-assisted diagnostic system showed lower sensitivity,specificity,positive predictive value,negative predictive value,accuracy,and area under the curve(AUC)for diagnosing MTC and PTC compared with physicians.Significant differences of AUC were found between senior physician and AI-assisted diagnostic system,as well as between attending physician and AI-assisted diagnostic system for diagnosing MTC and PTC(all P＜0.01),while no significant difference of AUC was between junior physicians and AI-assisted diagnostic system(both P＞0.05).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and AUC for AI-assisted diagnostic system for diagnosing MTC were all lower than those for diagnosing PTC,but the AUC was not significantly different(P＞0.05).Conclusion Ultrasonic thyroid AI-assisted diagnostic system had relatively high value for diagnosing MTC.