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*

Objective:To investigate the relationship between symptoms of vertigo and vestibular functions and short-term hearing outcomes in patients with flat descending sudden sensorineural hearing loss （SSNHL）. Methods:A retrospective review was conducted of the vestibular symptoms observed in 48 patients with unilateral flat-down sudden sensorineural hearing loss treated at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Symptoms of vertigo and the results of cervical vestibular-evoked myogenic potentials （cVEMP）, ocular VEMP （oVEMP）, caloric test and video head-impulse test （vHIT） were collected to determine whether these factors could predict therapeutic efficacy. Results:The symptoms of vertigo was not correlated with prognosis （P>0.05） or with abnormal vestibular functions （P>0.05）. Patients with abnormal cVEMP, oVEMP, caloric test or vHIT showed significantly lower effective rates （32.0%, 44.0%, 32.0%, and 24.0%, respectively）; the greater the number of abnormal tests, the poorer the outcome. Patients with all four tests abnormal gained only （3.13±15.97） dB HL in hearing recovery, whereas those with normal cVEMP, oVEMP, caloric test or vHIT showed better chances of hearing improvements by （29.22±20.31）, （31.18±21.59）, （26.17±21.31）, and （26.38±24.05） dB HL, respectively. Conclusion:Vestibular function effectively predicts prognosis in flat descending SSNHL. Patients with abnormal vestibular tests, regardless of symptoms of vertigo, responded poorly to treatment, whereas those with normal cVEMP, oVEMP, caloric test and vHIT results achieved better hearing recovery. Abnormal vestibular function implies more extensive and severe inner-ear lesions in patients with SSNHL.
Humans ; Male ; Female ; Retrospective Studies ; Prognosis ; Adult ; Middle Aged ; Vertigo/diagnosis* ; Hearing Loss, Sensorineural/diagnosis* ; Young Adult ; Hearing Loss, Sudden/diagnosis* ; Adolescent ; Aged ; Vestibular Evoked Myogenic Potentials

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*

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Methods: (i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, n = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, n = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, n = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), Aβ25-35 group (treated with 20 μmol/L Aβ25-35 for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L Aβ25-35 for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L Aβ25-35 for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR]. Results: (i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (P < 0.01) and the frequency of crossing the original platform was significantly increased (P < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (P < 0.01), and the width of synaptic gap was decreased (P < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (P > 0.05), and alleviated the cell viability decline induced by Aβ25-35 (P < 0.01). Western blot results showed that compared with Aβ25-35 group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased (P < 0.01), while the protein expression levels of SYP and PSD-95 were increased (P < 0.01). These effects were blocked by LY294002 (P < 0.01). Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD models and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Background::The effect of bariatric surgery on type 2 diabetes mellitus (T2DM) control can be assessed based on predictive models of T2DM remission. Various models have been externally verified internationally. However, long-term validated results after laparoscopic sleeve gastrectomy (LSG) surgery are lacking. The best model for the Chinese population is also unknown.Methods::We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016. The independent t-test, Mann–Whitney U test, and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups. We evaluated the predictive efficacy of each model for longterm T2DM remission after LSG by calculating the area under the curve (AUC), sensitivity, specificity, Youden index, positive predictive value (PPV), negative predictive value (NPV), and predicted-to-observed ratio, and performed calibration using Hosmer–Lemeshow test for 11 prediction models. Results::We enrolled 108 patients, including 44 (40.7%) men, with a mean age of 35.5 years. The mean body mass index was 40.3 ± 9.1 kg/m 2, the percentage of excess weight loss (%EWL) was (75.9 ± 30.4)%, and the percentage of total weight loss (% TWL) was (29.1 ± 10.6)%. The mean glycated hemoglobin A1c (HbA1c) level was (7.3 ± 1.8)% preoperatively and decreased to (5.9 ± 1.0)% 5 years after LSG. The 5-year postoperative complete and partial remission rates of T2DM were 50.9% [55/108] and 27.8% [30/108], respectively. Six models, i.e., "ABCD", individualized metabolic surgery (IMS), advanced-DiaRem, DiaBetter, Dixon et al’s regression model, and Panunzi et al’s regression model, showed a good discrimination ability (all AUC >0.8). The "ABCD" (sensitivity, 74%; specificity, 80%; AUC, 0.82 [95% confidence interval [CI]: 0.74–0.89]), IMS (sensitivity, 78%; specificity, 84%; AUC, 0.82 [95% CI: 0.73–0.89]), and Panunzi et al’s regression models (sensitivity, 78%; specificity, 91%; AUC, 0.86 [95% CI: 0.78–0.92]) showed good discernibility. In the Hosmer–Lemeshow goodness-of-fit test, except for DiaRem ( P <0.01), DiaBetter ( P <0.01), Hayes et al ( P = 0.03), Park et al ( P = 0.02), and Ramos-Levi et al’s ( P <0.01) models, all models had a satifactory fit results ( P >0.05). The P values of calibration results of the "ABCD" and IMS were 0.07 and 0.14, respectively. The predicted-to-observed ratios of the "ABCD" and IMS were 0.87 and 0.89, respectively. Conclusion::The prediction model IMS was recommended for clinical use because of excellent predictive performance, good statistical test results, and simple and practical design features.

Objective To screen differentially expressed miRNAs(DEMs)by comparing the expression of miRNAs in serum exosomes between Alzheimer's disease(AD)patients and healthy controls.Methods A total of 71 AD patients admitted to Department of Geriatric Neurology of Xiangya Hospital from March 2017 to August 2018 and another 71 healthy individuals who taking physical examination in the hospital during same period were recruited and assigned into AD and HC groups,respectively.Four AD patients and four healthy subjects were selected for high-throughput second-generation sequencing of exosome miRNAs.The results were analyzed to obtain the DEMs between them,and the top 4 DEMs were finally selected.Then real-time quantitative real-time PCR was applied for all the subjects to detect the expression of the 4 DEMs.Results High-throughput second-generation sequencing detected 775 miRNAs,and 44 DEMs were found with statistical difference between the 2 groups(P＜0.05).Compared with the HC group,34 miRNAs were up-regulated and 10 were down-regulated in the AD group.The top 4 DEMs were miRNA-148a-3p,miRNA-16-5p,miRNA-19b-3p and miRNA-483-5p.MiRNA-148a-3p was significantly up-regulated in the AD group than the HC group(P＜0.01),but there were no significant differences in the expression level in the other 3 DEMs between the 2 groups.ROC curve analysis showed that the area under the curve of miRNA-148a-3p was 0.7113(95％CI:0.622～0.801),with a sensitivity of 71.6％and a specificity of 69.7％.Conclusion Serum exosome miRNA-148a-3p can be used as a biomarker for the diagnosis of AD.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.