ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

Objective To investigate the correlation between thyroid hormone levels and cognitive function in schizophrenia(SCZ)patients with metabolic syndrome(MetS),as well as the mediating role of thyroid hormones in the relationship between MetS-related indicators and cognitive function.Methods A cross-sectional trial was conducted on 120 SCZ inpatients and outpatients(40 cases of MetS and 80 cases of non-MetS)and 80 healthy controls admitted in the Chongqing Mental Health Center from August 2023 to December 2024.Thyroid function indicators[Thyroid-stimulating hormone(TSH),triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),and free thyroxine(FT4)],MetS-related parameters[blood glucose,triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and waist circumference],Positive and Negative Syndrome Scale(PANSS)score,and Montreal Cognitive Assessment(MoCA)scores were collected.One-way ANOVA or Kruskal-Wallis rank sum test was applied to analyze the differences among the 3 groups,and LSD test or Bonferroni correction was performed for post hoc analysis.Pearson correlation analysis was conducted to assess the relationship between thyroid hormone levels and metabolic parameters as well as cognitive/clinical scale scores(MoCA,PANSS)in the MetS group.Results The MetS group exhibited significantly lower FT4 level(P<0.05)and MoCA score(P=0.001),but higher TSH level(P<0.05)and PANSS negative symptom score(P<0.001)when compared to the non-MetS group.Correlation analysis indicated that in the MetS group,TSH level was positively correlated with TG(r=0.672,P<0.001)and PANSS negative symptom score(r=0.458,P<0.05),and negatively with HDL-C(r=-0.377,P=0.017)and MoCA score(r=-0.667,P<0.001);FT4 level was positively correlated with MoCA score(r=0.534,P<0.001).In the non-MetS group,TSH level was positively correlated with PANSS negative symptom score(r=0.267,P=0.017)and negatively with HDL-C(r=-0.236,P=0.036),T3 was positively with waist circumference(r=0.268,P=0.017).No correlation was observed in FT4 level with HDL-C(r=-0.207,P=0.067)or MoCA score(r=0.216,P=0.055).Mediation analysis revealed that TSH partially mediated the association between TG and MoCA score,with a mediation effect accounting for 29.91%of the total effect.The mediating effect was not significant in the non-MetS group.Conclusion Abnormal elevation of TSH may serve as a critical link between MetS and cognitive impairment in SCZ patients,which providing novel insights into the mechanisms underlying cognitive dysfunction in the patients.

ObjectiveTo investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).MethodsWe explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.ResultsNetwork pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P .001), and interleukin-1β (P = .004) mRNAs in vivo.ConclusionsThe results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.

Objective To analyze the clinical,pathological,and endoscopic features of differentiated early gastric cancer,and to study predictors to identify and screen high risk patients with early gastric cancer submucosal infiltration.Methods A total of 172 patients with differentiated early gastric cancer treated by surgical or endoscopic submucosal dissection in our hospital from January 2017 to December 2022 were included,which were divided into the mucosal layer group(144 patients)and submucosal layer group(28 patients)based on postoperative pathology.The clinical,pathological,and white-light endoscopy(WLE)and linked color imaging(LCI)features of the 2 groups were compared.The color difference between the lesion and the surrounding mucosa was evaluated by using the Commission International de L'Eclairage(CIE)L*a*b*system.Indicators with significant differences were included to multifactor logistic stepwise regression analysis(forward method)for the identification and screening of predictors.Results A history of alcohol consumption(P=0.037),a history of smoking(P=0.035),thickening of the gastric wall on enhanced CT(P=0.032),a lesion located in the upper 1/3(P＜0.001)or middle 1/3(P=0.009)part of the stomach,depressed macroscopic type(P＜0.001),marked margin elevation(P=0.003),presence of fold changes(P=0.006),color difference ≥12.3 under WLE(P=0.003)and≥18.2 under LCI(P=0.002)were associated with submucosal infiltration.Multivariate analysis showed that lesions located in the upper 2/3 portion of the stomach(OR=5.463,95％CI:2.562-11.648,P＜0.001),depressed macroscopic type(OR=5.992,95％CI:1.624-22.100,P=0.007),marked margin elevation(OR=4.338,95％CI:1.124-16.747,P=0.033),and color difference ≥18.2 under LCI(OR=4.675,95％CI:1.342-16.288,P=0.015)were independent risk factors for infiltration of submucosal layer of lesions.Conclusion Lesions with depressed macroscopic type,marked elevated margins,located in the upper 2/3 part of the stomach,and having a large color difference from the surrounding mucosa under LCI are high-risk lesions for submucosal infiltration and require more aggressive intervention.

Objective:To observe the clinical and multimodal imaging features of eyes with acute macular neuroretinopathy (AMN) associated with the coronavirus disease 2019 (COVID-19).Methods:A retrospective study. From December 20, 2022 to January 17, 2023, a total of 29 patients (58 eyes) with COVID-19-associated AMN admitted to Department of Ophthalmology of Eye and ENT Hospital, Shanghai Medical College were included in the study. All the affected eyes underwent the best corrected visual acuity, color fundus photography, infrared fundus photography (IR), short-wavelength autofluorescence (SW-AF), near-infrared autofluorescence (NIL-AF), optical coherence tomography (OCT), and OCT angiography (OCTA). All patients were administered microcirculation-improving oral medication with 12 cases receiving adjunctive low-dose corticosteroid therapy. Follow-ups were conducted 1 to 3 months after the initial diagnosis, with a total of 19 cases (38 eyes) completing the one-month follow-up.Results:Out of the 29 cases, there were 9 males (18 eyes) and 20 females (40 eyes), all of whom experienced bilateral eye involvement. The age of the patients ranged from 12 to 47 years, with an average age of (29.9±9.5) years. The time from the onset of fever to the appearance of ocular symptoms was (2.52±2.01) days. Among the 58 affected eyes, there were 5 cases with retinal cotton wool spots, 2 cases with optic disc edema, and 1 case with parafoveal branch retinal vein occlusion. All affected eyes exhibited deep reddish-brown macular dark spots. IR revealed wedge-shaped, wedge-like, or "petaloid-like" dark areas involving the fovea and parafovea. SW-AF examination showed no obvious abnormality in 39 eyes. Weak autofluorescence dark area were consistent with IR in 19 eyes. NIR-AF examination showed spot-like or flaky self-fluorescent dark areas. OCT examination showed strong reflex lesions spreading vertically upward from the retinal pigment epithelium (RPE) layer in the macular area in the acute stage, showing typical "bean seedling" sign. OCTA revealed reduced blood flow density in the deep capillary plexus (DCP) of 50 eyes. Enface OCT displayed lesion areas that corresponded to the dark areas seen in IR. One month after the initial diagnosis, the condition improved in 18 eyes (47.4%, 18/38). Among the 5 eyes with cotton wool spots, regression of these spots was accompanied by loss of nerve fiber layer in 4 eyes. In cases with optic disc edema, the edema subsided. The "bean sprout" sign disappeared in all affected eyes, and the lesions became localized. The ellipsoid zone and/or interdigitation zone in the lesion areas were discontinuous.Conclusions:COVID-19-related AMN is characterized by distinctive features. IR fundus reveals wedge-shaped, wedge-like, or petaloid dark areas involving the fovea and parafovea. OCT displays strongly reflective lesions with vertical spread above the RPE. OCTA shows reduced blood flow density in the DCP of the retina.

Objective    To study the relationship between preoperative heart rate variability (HRV) and postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB). Methods    A retrospective analysis was performed on the clinical data of 290 patients who were admitted to the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command from May to September 2020 and received OPCAB. There were 217 males and 73 females aged 36-80 years. According to the incidence of POAF, the patients were divided into two groups: a non-atrial fibrillation group (208 patients) and an atrial fibrillation group (82 patients). The time domain and frequency domain factors of mean HRV 7 days before operation were calculated: standard deviation of all normal-to-normal intervals (SDNN), root mean square of successive differences, percentage difference between adjacent normal-to-normal intervals that were greater than 50 ms, low frequency power (LF), high frequency power (HF), LF/HF. Results    The HRV value of patients without POAF was significantly lower than that of patients with POAF (P<0.05). The median SDNN of the two groups were 78.90 ms and 91.55 ms, respectively. Age (OR=3.630, 95%CI 2.015-6.542, P<0.001), left atrial diameter (OR=1.074, 95%CI 1.000-1.155, P=0.046), and SDNN (OR=1.017, 95%CI 1.002-1.032, P=0.024) were independently associated with the risk of POPAF after OPCAB. Conclusion     SDNN may be an independent predictor of POAF after OPCAB.

We report a case of a female teenage with monogenic diabetes mellitus caused by glucokinase regulator (GCKR) gene mutation who presented with diabetic ketosis and misdiagnosed as type 1 diabetes. The patient was treated with insulin for 3 years since diagnosis. The islet function was well preserved, but polycystic ovary syndrome was developed. Whole-exome gene sequencing revealed a GCKR gene c. 69delG heterozygous mutation. After molecular diagnosis, the insulin dosage was gradually reduced to full cessation, and only metformin sustained-release tablets were taken to control blood glucose. It is necessary to regular evaluate islet function of patient with type 1 diabetes, and genetic test is of significance for accurate diagnosis and treatment.

Objective:To evaluate the long-term results of combined ganglion plexus ablation(GPA) during radiofrequency ablation(RF) with long-standing persistent atrial fibrillation(LSP-AF).Methods:This retrospective study sample consisted of 268 patients with LSP-AF underwent valve operations concomitant RF maze Ⅳ procedure. Data were collected prospectively on perioperative outcomes, rhythm status, survival, and clinical events. Propensity score matching conducted by RF and RF+ GPA resulted in 102 patients per group.Results:Independent predictors for rhythm success at 1 year were combined GPA( OR=0.205, P=0.005), smaller left atrium size( OR=1.091, P=0.000); at 5-year and 8-year were a shorter history of AF( OR=1.069, P=0.023; OR=1.066, P=0.030), and smaller left atrium size( OR=1.091, P=0.000; OR=1.086, P=0.000). After matching, RF+ GPA group had significantly higher sinus rhythm(SR) without antiarrhythmic drugs(AADs) at 6 months(91.3% vs. 79.8%, P=0.026), 1-year(90.2% vs. 78.5%, P=0.028), but there were no difference between the two groups at 5-year(64.8% vs. 64.4%, P=0.956), and 8-year(53.3% vs. 50.6%, P=0.711). During the 6 postoperative months, fewer patients in the RF+ GPA group underwent follow-up cardioversions(2.0% vs. 8.8%, P=0.030). Actuarial survival curves did not differ significantly between the 2 groups( HR=1.327, 95% CI 0.4633-3.802, P=0.598). Conclusion:The combination of GPA can be effective at the early postoperative stage for SR restoration in Maze Ⅳ procedures for the treatment of LSP-AF in heart valve surgeries, particularly for lower AADs use and lower cardioversions. However, this effect will gradually diminish after one year.