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 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.

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.

Objective:To induce an experimental autoimmune encephalomyelitis(EAE)model by MOG-specific TCR trans-genic mice(2D2TCR transgenic mice),and to investigate effect of exogenous ERMAP on T cells in spleen of MOG35-55-induced 2D2TCR transgenic mice.Methods:EAE models were established in two groups of 2D2TCR transgenic mice(Control-Ig treatment for control group and ERMAP-Ig fusion protein treatment for experimental group),with 9 mice per group.Severity of spinal cord injury of MOG35-55-induced EAE in mice was assessed based on daily clinical scores(DAI),HE and LFB staining results;autoreactive T cells(CD4+Vα3.2+Vβ11+),T cell proliferation activation indicators CD69(CD4+Vα3.2+Vβ11+CD69+)and Ki67(CD4+Vα3.2+Vβ11+Ki67+),Treg(CD4+Vα3.2+Vβ11+CD25+Foxp3+)and Th17 cells(CD4+Vα3.2+Vβ11+IL-17A+)in spleen were detected by flow cytome-try;IL-17A,IL-6,IFN-γ and TGF-β expressions in spinal cord tissues were detected by qRT-PCR.Results:In MOG35-55-induced 2D2TCR transgenic mouse EAE model,ERMAP-Ig fusion protein treatment group showed milder inflammatory infiltration and demye-lination in spinal cord,decreased proportion of autoreactive T cells,decreased proportion of activated and proliferating T cells,increased proportion of Treg,inhibition of Th17 cell differentiation,less inflammatory cell aggregation and cytokine production,and increased expression of anti-inflammatory factors in spinal cord.Conclusion:ERMAP may be involved in development of EAE in 2D2TCR transgenic mice by inhibiting T cell proliferative activation and promoting Treg cell production.

Objective:To investigate the effects of decellularised extracellular matrix material(dECM)extract on macrophage survival,migration,phagocytosis,pro-inflammatory factor expression and ROS production.Methods:CCK-8 method was used to detect whether the extract of dECM material had cytotoxicity on macrophages;effects of dECM material extracts on macrophage recruit-ment and chemotaxis were examined by Transwell migration assay;effects of dECM material extract on macrophage phagocytosis were detected by pHrodo staining;effects of dECM material extract on expression of pro-inflammatory genes and pro-inflammatory specific functional molecules were detected by RT-qPCR and immunofluorescence staining;detection of the effect of dECM material extracts on macrophage ROS production by the DCFH-DA fluorescent probe approach.Results:Compared with DMEM complete medium,①CCK-8 assay showed that dECM material extract had no toxic effect on macrophages,and could promote the formation of macrophage colonies;②pHrodo staining assay showed that dECM material extract did not affect phagocytosis of macrophages;③Transwell migra-tion assay showed that dECM material extract did not promote macrophage migration;④RT-qPCR results showed that dECM material extracts were able to down-regulate gene expressions of pro-inflammatory cytokines and specific functional molecules;⑤Flow cytome-try results showed that dECM material extract could reduce the production of ROS by macrophages.dECM material extract had excel-lent biocompatibility for macrophages.Conclusion:dECM material extract is non-toxic to macrophages and is able to reduce macro-phage pro-inflammatory gene expression and ROS production.

Immune cells are formed by the proliferation and differentiation of hematopoietic stem cells in the bone marrow,in-cluding lymphocytes,macrophages,etc,which participate in the immune defense,immune stability and immune monitoring of the body,and are an indispensable basic component of the immune system.Basic helix-loop-helix family member E40(BHLHE40)has been shown to play an important role in adipogenesis,tumorigenesis,circadian rhythm and hypoxia response.Recently,it was found that BHLHE40 plays a key role in the cell cycle,proliferation and cytokine production of immune cells.This article will review the discovery,naming,structure,and mechanism of BHLHE40 in various periods,as well as it's research progress in immune cells,in order to provide new target for the treatment of immune-related diseases at the genetic level.

Objective To analyze the risk factors of tracheal reintubation after total aortic arch replace-ment and to provide evidence for the prevention of tracheal reintubation after total aortic arch replacement.Methods From January 1,2019 to June 31,2020,162 patients who underwent total aortic arch replacement in the Department of Cardiac Surgery of a tertiary grade-A hospital in Guangdong Province were randomly selected and divided into reintubation group(n=27)and control group(n=135)based on the occurrence of tracheal reintubation.The risk factors were analyzed by univariate and multivariate logistic regression.Results Among the 162 patients,27 cases(16.7%)had tracheal reintubation.Compared with those in the control group,the length of ICU stay and hospitalization cost in the reintubation group were significantly increased(P<0.001).Univariate analysis indicated that there were significant differences in terms of age,glomerular filtration rate,diabetes mellitus,venti-lator time,pulmonary infection,liver insufficiency,hypoxemia,delirium and cerebrovascular accident(P<0.05).Multivariate analysis showed age(OR=1.069,P=0.038),pulmonary infection(OR=5.227,P=0.047),delirium(OR=7.079,P=0.011),and ventilator use time(OR=1.006,P=0.001)were independent risk factors for tracheal reintubation after total arch replacement.A regression equation was established as follows:[Logit(P)=-8.885+0.066×age+1.654×pulmonary infection+1.957×delirium+0.006×time]of first ventilator use.The area under the ROC curve of the subjects in this model was 0.931(95%CI:0.884～0.979),P<0.001;The results of Hosmer-Lemeshow test(χ2=4.76 and P=0.782)indicated that the model had high accuracy.Conclusion Age,pulmonary infection,delirium and ventilator use time are independent risk factors for tracheal reintubation after total aortic arch replacement.

Objective:To describe the trend of changes in the disease burden of age-related hearing loss in China and globally from 1990 to 2021,to forecast the prevalence and years lived with disability(YLD)rates of age-related hearing loss from 2022 to 2036,and to provide a reference for the prevention and control of the disease burden associated with age-related hearing loss.Methods:Using the Global Burden of Disease 2021(GBD2021)data,this study selected age-standardized prevalence rate(ASPR)and YLD as indicators.The disease burden and long-term trends of age-related hearing loss in China and globally from 1990 to 2021 were described by different socio-demographic index(SDI)and gender.Joinpoint regression was used to calculate the average annual percent change(AAPC)to assess the trend changes in the disease burden.Decomposition analysis was applied to explore the relative im-pacts of aging,population growth,and epidemiological changes on the variation in disease burden.An autoregressive integrated moving average(ARIMA)model was used to forecast the age-standardized pre-valence rate and YLD rates from 2022 to 2036.Results:The prevalence of age-related hearing loss in China in 2021 was 82 162.49(73 288.08-89 187.21)per 100 000,higher than the global SDI level of 66 238.16(59 982.54-72 669.82)per 100 000,the high SDI region's level of 57 650.42(52 059.12-63 889.02)per 100 000,the upper-middle SDI region's level of 69 115.59(62 494.18-75 340.64)per 100 000,the middle SDI region's level of 72 365.56(65 181.43-78 912.01)per 100 000,the lower-middle SDI region's level of 64 439.66(58 368.22-71 468.27)per 100 000,and the low SDI region's level of 61 725.25(55 749.18-68 477.67)per 100 000.The age-related hearing loss YLD rate in China was 2 762.98[95％uncertainty interval(UI):1 855.28-3 880.68]per100000,higher than the global SDI level of 2 236.75(95％UI:1 511.56-3 155.88)per 100 000,the high SDI region's level of 1 805.79(95％UI:1 212.69-2 577.17)per 100 000,the upper-middle SDI re-gion's level of 2 316.58(95％UI:1 557.53-3 274.87)per 100 000,the middle SDI region's level of 2 480.99(95％UI:1 678.17-3 489.24)per 100 000,the lower-middle SDI region's level of 2 313.28(95％UI:1 578.35-3 271.50)per 100 000,and the low SDI region's level of 2 383.55(95％UI:1 623.66-3 365.68)per 100 000.From 1990 to 2021,both the prevalence and YLD rate of age-related hearing loss in China showed an increasing trend,rising by an average of 0.18％(95％CI:0.16％-0.19％)and 0.29％(95％CI:0.27％-0.30％)per year,respectively.The rates of in-crease in prevalence were the same for both men and women,with men showing a 0.18％increase(95％CI:0.17％-0.19％,P＜0.001)and women showing a 0.18％increase(95％CI:0.16％-0.19％,P＜0.001).However,the YLD rate increase was faster in men than in women,with men experiencing a 0.32％increase(95％CI:0.27％-0.37％,P＜0.001)and women experiencing a 0.27％increase(95％CI:0.26％-0.28％,P＜0.001).Decomposition analysis showed that population growth was the main factor driving the increase in prevalence and YLD rate globally and across different SDI regions.However,aging was the primary factor contributing to the increase in prevalence and YLD rate in China.ARIMA model predictions suggested that the prevalence and YLD rate of age-related hearing loss would continue to rise from 2022 to 2036,with the predicted prevalence and YLD rate in 2036 reaching 89 723.99 per 100 000 and 2 872.47 per 100 000,respectively.Conclusion:The prevalence and disease burden of age-related hearing loss in individuals aged 60 and above in China rank first globally.From 1990 to 2021,both the prevalence and YLD rate of age-related hearing loss have shown a continuous upward trend,consistently surpassing the levels observed in various SDI regions worldwide.The prevalence and disease burden of age-related hearing loss are particularly significant among elderly men.Moreover,projections indicate that the disease burden of age-related hearing loss will continue to rise over the next 15 years.Therefore,it is urgent to pay close attention to age-related hearing loss in this specific population,and early intervention measures are crucial to reduce the disease burden associated with age-related hearing loss.