Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Objective To compare the pathological diagnosis rate, number of punctures, and applicability to different lesion locations between a fork-tip biopsy needle and a conventional needle. Methods A retrospective collection of data was conducted on 137 patients who underwent endoscopic ultrasound (EUS)-guided fine needle biopsy (novel needle group, n=12) or aspiration (conventional needle group, n=125) at Zhongshan Hospital, Fudan University from January to August 2023. After propensity score matching at a ratio of 1∶5, there were 12 patients in the novel needle group and 60 patients in the conventional needle group. The pathological diagnosis rate and number of punctures were compared between the two groups. The stratified analyses on the size and location of lesions were performed. Results After matching, the pathological diagnosis rate was 91.7% (11/12) in the novel needle group, with a median of 2 punctures; the rate was 61.7% (37/60) in the conventional needle group, with a median of 3 punctures. No statistically significant differences in pathological diagnosis rate and number of punctures were observed between the two groups. Subgroup analysis showed that for lesions ≥20 mm, there was no significant difference in the number of punctures between the novel and conventional needles. The novel needle achieved a significantly higher pathological diagnosis rate for subepithelial tumors compared with the conventional needle (100.0% vs 30.4%, P＝0.019), whereas no significant differences were found for pancreatic masses or lymph node lesions. Conclusions Compared with EUS-guided aspiration using the conventional needle, EUS-guided biopsy using the novel fork-tip needle shows a trend toward a higher pathological diagnosis rate, with particular advantages in subepithelial tumors.

ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through regulating ferroptosis， and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients （10 cases each） were collected and divided into control group， eutopic group， and EMs group. Hematoxylin-eosin （HE） staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4）. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of malondialdehyde （MDA）， ferrous ion （Fe²⁺）， GPX4 and glutathione （GSH） in endometrial tissues， as well as serum levels of Fe²⁺， GPX4 and GSH. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of SLC7A11， GPX4， transferrin receptor （TFR） and ferritin heavy chain 1 （FTH1）. In the in vitro experiment， primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 （CCK-8） was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species （ROS） was measured， and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments， an EM rat model was established， and the rats were randomly assigned to the sham operation group， EMs group， low-dose Luoshi Neiyi Formula group （7.87 g·kg^-1）， high-dose Luoshi Neiyi prescription group （15.74 g·kg^-1）， and danazol group （42 mg·kg^-1）. Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators （GPX4， Fe²⁺， MDA， GSH） as well as ferroptosis-related mRNAs （GPX4， SLC7A11， FTH1） were analyzed， and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium， ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium， the contents of MDA， ROS， and Fe²⁺ decreased， while GPX4 level increased， and the mRNA expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. In serum， the levels of GPX4 and Fe²⁺ were elevated， whereas the GSH level declined， suggesting abnormalities in ferroptosis-related pathways in ectopic lesions （P<0.05， P<0.01）. After intervention with Luoshi Neiyi prescription-containing serum， the intracellular ROS level in ectopic endometrial stromal cells was elevated， the mRNA expression of SLC7A11 and GPX4 was downregulated， and TFR mRNA expression was upregulated （P<0.05， P<0.01）. Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats， respectively， compared with their corresponding control groups， and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance， with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI（16∶0/17∶0） and PI［18∶2（9Z，12Z）］ were negatively correlated with GPX4 and positively correlated with MDA， while 17α-hydroxyprogesterone was positively correlated with GPX4， SLC7A11， and FTH1 q<0.05）. ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway， and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively， these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.

ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through regulating ferroptosis， and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients （10 cases each） were collected and divided into control group， eutopic group， and EMs group. Hematoxylin-eosin （HE） staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4）. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of malondialdehyde （MDA）， ferrous ion （Fe²⁺）， GPX4 and glutathione （GSH） in endometrial tissues， as well as serum levels of Fe²⁺， GPX4 and GSH. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of SLC7A11， GPX4， transferrin receptor （TFR） and ferritin heavy chain 1 （FTH1）. In the in vitro experiment， primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 （CCK-8） was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species （ROS） was measured， and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments， an EM rat model was established， and the rats were randomly assigned to the sham operation group， EMs group， low-dose Luoshi Neiyi Formula group （7.87 g·kg^-1）， high-dose Luoshi Neiyi prescription group （15.74 g·kg^-1）， and danazol group （42 mg·kg^-1）. Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators （GPX4， Fe²⁺， MDA， GSH） as well as ferroptosis-related mRNAs （GPX4， SLC7A11， FTH1） were analyzed， and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium， ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium， the contents of MDA， ROS， and Fe²⁺ decreased， while GPX4 level increased， and the mRNA expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. In serum， the levels of GPX4 and Fe²⁺ were elevated， whereas the GSH level declined， suggesting abnormalities in ferroptosis-related pathways in ectopic lesions （P<0.05， P<0.01）. After intervention with Luoshi Neiyi prescription-containing serum， the intracellular ROS level in ectopic endometrial stromal cells was elevated， the mRNA expression of SLC7A11 and GPX4 was downregulated， and TFR mRNA expression was upregulated （P<0.05， P<0.01）. Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats， respectively， compared with their corresponding control groups， and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance， with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI（16∶0/17∶0） and PI［18∶2（9Z，12Z）］ were negatively correlated with GPX4 and positively correlated with MDA， while 17α-hydroxyprogesterone was positively correlated with GPX4， SLC7A11， and FTH1 q<0.05）. ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway， and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively， these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.

Objective To investigate the clinical efficacy of the median and paramedian approaches in ultrasound-guided combined spinal-epidural anesthesia for patients with hemorrhoidectomy and to evaluate the differences between the two techniques.Methods A retrospective analysis was performed on 90 AIDS patients who underwent hemorrhoidectomy under combined spinal-epidural anesthesia from February 2024 to March 2025.The patients were categorized into two groups based on the ultrasound-guided puncture approach:a midline approach group and a paramedian approach group.In the midline approach group,anatomical landmarks such as the spinous process space,facet joint,and transverse process were identified in the transverse axial plane for accurate localiza-tion.The puncture site was determined as the midpoint of the interspinous space along the spinal midline,and an out-of-plane puncture technique was utilized.In the paramedian approach group,positioning was performed by scanning the lamina in the sagittal oblique plane.The dorsal complex structure space with the clearest visibility was centered under the probe,and an in-plane puncture technique was applied,with the needle advanced from the caudal to the cephalad direction to complete the combined spinal-epidural procedure.Data regarding puncture performance,complications,and anesthetic efficacy were systematically recorded and assessed for both groups.Results Intergroup analysis demonstrated that the paramedian approach group exhibited significantly fewer total puncture attempts and a higher success rate on the first attempt(P<0.05).No significant differences were observed between the two groups regarding the need to change puncture levels or modify the puncture approach(P>0.05).The midline approach group showed a significantly higher incidence of paresthesia and a greater frequency of post-operative puncture site tenderness at two days post-surgery compared to the paramedian approach group(P<0.05).Anesthetic efficacy was comparable between the two groups,with no statistically significant difference detected(P>0.05).Conclusions In hemorrhoidectomy procedures for AIDS patients,the paramedian approach demon-strates advantages over the median approach in terms of puncture success and reduced complications associated with ultrasound-guided combined spinal-epidural anesthesia.However,no significant difference in anesthetic efficacy is observed between the two approaches.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.

Objective To understand the current status of work-related musculoskeletal disorders (WMSDs) among operating room doctors,thereby analyzing its effect on mental health. Methods A total of 1013 doctors in the operating rooms of 30 hospitals in 24 provinces from September to December 2022 were selected by cross-sectional survey method. The domestic musculoskeletal disease questionnaire was used to investigate the occurrence of WMSDs in operating room doctors,the symptom check list-90 (SCL-90) was used to evaluate the psychological status of operating room doctors,the relationship between WMSDs related items and SCL-90 scores was analyzed,the correla-tion between the rest time of each shift and SCL-90 factors was analyzed by Pearson method,and the influencing factors of mental health of operating room doctors were analyzed by multivariate Logistic regression.Results A total of 1100 questionnaires were distributed and 1013 valid questionnaires were recovered,with an effective rate of 92.10％. The incidence of WMSDs among operating room doctors in the past 1 year was 95.06％. The body parts with incidences of WMSDs from high to low were as follows:waist (36.92％),neck (35.54％),shoulder (33.56％),and upper back (32.77％). In the past 1 year,the SCL-90 scores and total scores of patients with musculoskeletal pain in various body parts,keeping the same back posture for a long time while work,bending the back at the same time of turning frequently while working,bowing the head for a long time while working,and bending the knee for a long time while working were significantly higher than those who were without the above conditions (P<0.05). Shorter rest time of each shift and longer periods of keeping the same back posture were the risk factors for the development of mental illness in operating room doctors. Conclusion The incidence of WMSDs in operating room doctors is high,which can influence the mental health of operating room doctors. Therefore,operating room doctors should avoid keeping the same back posture for a long time,bending the back at the same time of turning frequently,bowing the head for a long time,and bending the knee for a long time while working,and increase the rest time of each shift,in order to improve the mental condition of the operating room doctors.

Objective:To investigate the correlation between platelet alloantibodies and CD8+T cell with platelet desialylation and apoptosis in platelet transfusion refractoriness(PTR).Methods:The expression of RCA-1,CD62P and Neu1 on platelets were detected in 135 PTR patients and 260 healthy controls.The ability of PTR patients'sera with anti-HLA antibody,anti-CD36 antibody and antibody-negative groups to induce platelet desialylation and apoptosis,and the potential effect of FcγR inhibitors on desialylation and apoptosis were evaluated.Additionally,the association between CD8+T cells and platelet desialylation in patients was analyzed.Results:The expression of RCA-1 and Neu1 on platelets in PTR patients were significantly higher than those in healthy donors(P＜0.05),but were not related to platelet alloantibody(P＞0.05).The sera of PTR patients generally induced platelet desialylation in vitro(P＜0.05),with no significant differences among the groups(P＞0.05).However,the sera with anti-CD36 antibodies could induce platelet apoptosis significantly higher than that in the anti-HLA antibody group and antibody-negative group in vitro(P＜0.05).In PTR patients with anti-CD36 antibodies,platelet apoptosis was dependent on FcγR signaling,while desialylation is not.Moreover,CD8+T cells in PTR patients were significantly associated with platelet desialylation(P＜0.05).Conclusion:Platelet desialylation is a common pathological phenomenon in PTR patients,which involves the participation of CD8+T cell,but isn't associated with platelet alloantibody;while anti-CD36 antibodies have potential clinical significance in predicting platelet apoptosis in PTR patients.