Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

AIM: To investigate the influence of pterygium thickness and area on corneal refractive status.METHODS: Prospective longitudinal study. A total of 60 cases(60 eyes)of pterygium patients admitted to our hospital from January 2024 to September 2024 were randomly selected. All patients underwent pterygium excision combined with pedicle conjunctival flap transplantation for treatment. Optical coherence tomography(OCT)was used to measure the preoperative thickness of patient's pterygium, and a digital slit lamp microscope was used to measure the area of pterygium. The corneal refractive status(degree of corneal astigmatism and average curvature)and changes in uncorrected visual acuity of patients before surgery, 1 d, 1, and 3 mo after surgery were compared. The relationship between preoperative thickness and area of pterygium in patients and corneal refractive status indicators at different postoperative time points were analyzed, and Logistic regression was used to analyze the impact of pterygium thickness and area on postoperative visual improvement in patients.RESULTS: All patients completed follow-up after surgery for 3 mo. At 3 mo after surgery, visual acuity improved in 21 eyes(35%). The results of bivariate Pearson correlation analysis showed that the thickness and area of pterygium positively correlated with the degree of corneal astigmatism and uncorrected visual acuity before surgery and 1 d, 1, and 3 mo after surgery(all P<0.05), and negatively correlated with the average corneal curvature before surgery and 1 d, 1, and 3 mo after surgery(all P<0.05). Logistic regression analysis showed that the thickness and area of pterygium before surgery, high degree of corneal astigmatism, and low uncorrected visual acuity(large LogMAR value)were all risk factors for poor postoperative visual improvement in patients(OR>1, P<0.05). The large average corneal curvature before surgery was a protective factor for poor postoperative visual improvement in patients(OR<1, P<0.05).CONCLUSION: The increase in thickness and area of pterygium can, to some extent, improve corneal astigmatism, reduce the average curvature of the cornea, and affect postoperative visual recovery.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

The high pressure generated from urinary tract obstruction can cause damage to the tissues and cells of the urinary tract. Persistent damage can induce urinary tract fibrosis, ultimately resulting in the loss of urinary tract function and severe clinical problems. In recent years, the role of a novel mechanosensitive ion channel in urinary tract fibrosis, Piezo1, has drawn due attention. This review systematically summarizes the mechanisms of Piezo1. In upper urinary tract fibrosis, Piezo1 participates in fibrotic process through the Calcium-Calpain2-integrin β1-adhesion protein pathway and Piezo1-p38MAPK-YAP signaling pathway. In lower urinary tract fibrosis, Piezo1 mediates bladder fibrosis via the YAP1 and TGF-β1/Smad pathways, and may contribute to prostate cancer-associated urethral obstruction through the Akt/mTOR signaling pathway. This study elucidates the critical roles of Piezo1 in urinary tract fibrosis, providing a theoretical foundation for developing novel Piezo1targeted therapeutic strategies. Future research can leverage advanced technologies such as microfluidic organ-on-a-chip system to explore the precise regulatory mechanisms of Piezo1, thus offering new insights for the clinical management of urinary stricture diseases.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Objective To investigate the pathogenesis of high-altitude cerebral edema(HACE)and develop new therapeutic strategies.Methods Male Sprague-Dawley(SD)rats of 6 weeks old were selected and placed in a hypobaric chamber.The rats were exposed to the high-altitude environment of 7000 m above sea level for 3 days for HACE modeling.Whether the HACE model was successfully established in the rats was evaluated by measuring brain water content,the degree of disruption to the blood-brain barrier(BBB),and brain tissue Nissl staining.The experimental animals were divided into four groups,with 28 rats in each group.The blank control group was exposed to a normobaric and normoxic environment simulating the conditions at 500 m above sea level for 3 d.The other groups,including a model group(the HACE group),a bumetanide group(the positive control group),and a XH-6003 treatment group,were placed at an altitude of 7 000 m above sea level and were injected with normal saline,bumetanide,and XH-6003,a new type of Na-K-2C1 cotransporter 1(NKCC1)inhibitor,via the tail vein,respectively,twice daily for 3 d.The experimental animals were taken out of the hypobaric chamber for testing after 3 d.The primary outcome measures included brain water content,BBB permeability,changes in brain tissue morphology,and the expression levels of aquaporin-4(AQP4)and NKCC1.The secondary outcome measures included behavioral changes,apoptosis,and oxidative stress markers.Results The HACE rat model was successfully established.The model group exhibited increased brain water content(P＜0.0001),BBB disruption(P＜0.0001),impairment in learning skills and memory(P＜0.001),and anxiety/depression-like behaviors(P＜0.01).qPCR results showed significantly increased expression of NKCC1 and AQP4 in the brain tissue of the model group(P＜0.01).Pathology examination revealed neuronal and glial cell damage in the hippocampus of the model group(P＜0.01).Treatment with XH-6003,the NKCC1 inhibitor,reversed brain water content,BBB disruption,and neuronal and glial cell damage to a certain degree(P＜0.05),decreased the expression of NKCC1 and AQP4 in the brain tissue(P＜0.01),and inhibited apoptosis-related proteins.Among the oxidative stress indices,only glutathione(GSH)showed improvement(P＜0.001).Rats treated with XH-6003 showed functional improvement only in the time spent exploring novel objects,while other behavioral outcomes remained unchanged.Conclusion HACE is associated with the activation of the NKCC1/AQP4 pathway.Inhibition of this pathway alleviates brain edema,BBB disruption,and neuronal and glial cell damage.These findings suggest that XH-6003 holds potential as a therapeutic strategy for HACE at the cellular and molecular levels,but its effects in improving HACE-related behavioral disorders warrant further investigation.

Paranasal sinuses,also known as nasal sinuses,are a collective term for the air-filled cavities surrounding the nasal cavity within the skull.The paranasal sinuses comprise the maxillary sinuses,ethmoid sinuses,frontal sinuses,and sphenoid sinuses,which are bilaterally symmetrical,totaling four pairs.Due to the deep-seated anatomical location of the paranasal sinuses within the skull,accurate measurement has been historically challenging,resultsing in relatively limited early investigations in this field.In recent years,with the continuous advancement of imaging technologies,research on the morphology of the paranasal sinuses has progressively increased.In this paper we provides a systematic review of domestic and international research on the variations of paranasal sinuses among different populations,factors influencing their growth and development,evolutionary characteristics,and measurement method-ologies.Furthermore,a concise retrospective analysis and future prospects for studies on the paranasal sinuses within the domestic context are provided.

Objective:To analyze the risk factors for in-hospital malignant ventricular arrhythmia (MVA) in acute myocardial infarction (AMI) and to construct and validate a risk prediction model.Methods:This study was a retrospective cohort study. Patients aged≥18 years who were admitted to Qilu Hospital of Shandong University with a diagnosis of AMI and underwent coronary angiography (CAG) from May 2016 to March 2023 were selected, and the patients' clinical routine test indicators and CAG results were collected. Univariate and bidirectional stepwise logistic regression were used to screen out the risk factors for constructing the best prediction model. The prediction model was constructed by combining the results of multivariate logistic regression. The Hosmer-Lemeshow test and ROC curve, calibration curve, and decision curve were drawn to evaluate the model. The nomogram was drawn to visualize the model, and the Bootstrap self-sampling method was used for internal validation. The ROC curve was drawn to evaluate the predictive performance of each risk factor and prediction model. Finally, a multicollinearity test was performed.Results:Among the 4 205 patients finally included in the study, 115 patients (2.735%) developed MVA during hospitalization. The predictive factors screened out included age (X1), diastolic blood pressure (X2), respiratory rate (X3), blood glucose (X4), serum potassium (X5), logarithmic NT-proBNP (X6), myocardial infarction type (NSTEMI=X7, unclassified=X8), J wave (X9), Killip grade (Ⅱ=X10, Ⅲ=X11, Ⅳ=X12), and the regression equation was ln(p/1-p)=-4.699+0.029×X1-0.012×X2+0.059×X3+0.148×X4-1.175×X5+0.866×X6-1.427×X7-0.475×X8+0.758×X9+0.294×X10+0.902×X11+1.815×X12. The area under the ROC curve (AUC) of the model was 0.855 (95% CI: 0.816-0.894), and the Hosmer-Lemeshow test ( χ2=14.178, P=0.077) and the calibration curve showed that the predicted probability was consistent with the actual probability. The probability threshold of 0% to 65% had a better clinical net benefit. The area under the internal validation ROC curve (AUC) was 0.855, 95% CI: 0.813-0.891. The prediction performance of the nine variables was stronger than that of any single variable. There was no multicollinearity between the variables. Conclusions:Age, diastolic blood pressure, respiratory rate, blood glucose, serum potassium, NT-proBNP, type of AMI, J wave, and Killip class are forecasting indicator for in-hospital MVA in AMI. The risk prediction model based on the above factors has good predictive performance.

Objective To evaluate the role and potential mechanism of apolipoprotein E(APOE)in drug resistance of colon cancer by bioinformatic tools and cellular experiments.Methods After downloading the microarray dataset GSE196900 from the GEO database,the online tool GEO2R was used to identify genes that were expressed differently in the drug-resistant and control groups.The differently expressed genes were then examined for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The STRING database and Cytoscape software were used to build protein-protein interaction(PPI)networks and find hub genes.Hub genes'predictive significance in colon cancer was further assessed.Western blod and qRT-PCR were used to identify changes in APOE expression,whereas Transwell was used to identify changes in the colon cancer cells'capacity for invasion and migration.Results The analysis of GO and KEGG enrichment revealed that the differential genes derived from the GSE196900 dataset were primarily focused on receptor-ligand activity and cytokine-cytokine receptor interaction pathways.Using the CytoNCA plug-in in Cytoscape software,ten hub genes were obtained through PPI construction.Of these,the prognosis of the patients with colon cancer was negatively correlated with the expression of the APOE gene(P<0.05)and the overexpression of the APOE gene might significantly increase the migration and nvasivenessability of colon cancer cells(P<0.05).Conclusion The increased expression of APOE significantly promotes the migration and invasion ability of colon cancer cells,which may be one of the mechanisms by which APOE gene promotes tumor progression in the patients with colon cancer.