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.

This article explores the pathogenesis ， evolution and the prevention-treatment strategies of hypertension-related coronary microvascular dysfunction （H-CMD） from the collateral disease theory. Long-term hypertension may lead to coronary microvascular vasomotor imbalance， endothelial injury， vascular remodeling， microthrombosis， reduced perfusion reserve， and microvascular rarefaction， suggesting a progressive pathological process from functional disturbance to structural injury， collateral obstruction， and insufficient repair. Collateral disease theory emphasizes the network-like distribution， gradual branching， and permeating and nourishing functions of collaterals， as well as the concept that prolonged disease enters the collaterals， providing a reference for understanding coronary microcirculatory dysfunction and malnourishment of heart collaterals. Accordingly， the traditional Chinese medicine （TCM） pathogenesis of H-CMD can be summarized into four interconnected stages： Collateral Qi stagnation， scorching injury of collateral vessels， phlegm-stasis obstruction of collaterals， and collateral deficiency with malnourishment. Collateral Qi stagnation is the initiating stage， mainly corresponding to abnormal coronary microvascular vasomotor regulation and endothelial dysfunction. Scorching injury of collateral vessels represents the developmental stage and is closely associated with inflammation， oxidative stress， and endothelial barrier injury after Qi stagnation transforms into fire. Phlegm-stasis obstruction of collaterals represents the prolonged stage and may aggravate vascular wall thickening， luminal stenosis， microthrombosis， and insufficient microcirculatory perfusion. Collateral deficiency with malnourishment is the late-stage outcome， reflecting deficiency of healthy Qi， collateral damage， Qi-blood malnourishment， and weakened repair capacity， mainly manifested as microvascular rarefaction， occlusion， and microcirculatory homeostatic imbalance. Therapeutically， stage-based syndrome differentiation and the combined strategy of dredging and nourishing collaterals should be emphasized. Specifically， promoting Qi movement， resolving stagnation， soothing the liver， and harmonizing collaterals should be adopted in the early stage. Clearing heat， pacifying the liver， calming and protecting collaterals should be adopted in the developmental stage. Resolving phlegm， activating blood， and dredging collaterals should be implemented in the prolonged stage. Supplementing Qi， nourishing blood， tonifying the kidney， regulating balance， strengthening healthy Qi， and nourishing collaterals should be carried out in the late stage. Related formulas and medicinals may act by regulating the nitric oxide/endothelin-1（NO/ET-1） balance， inhibiting inflammation and oxidative stress， improving microcirculatory perfusion， and promoting angiogenesis and endothelial repair. Collateral disease theory may provide a theoretical basis for understanding the dynamic pathogenesis of H-CMD and for stage-based TCM intervention.

Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

(rsFC)and their relationship with negative symptoms in schizophrenia patients with predominant negative symptoms(PNS).Methods Fifty-four schizophrenia patients with PNS and sixty-one healthy controls underwent resting-state functional magnetic resonance imaging(fMRI)scans.Data were collected on general demographic information,the Positive and Negative Syndrome Scale(PANSS),the Scale for the Assessment of Negative Symptoms(SANS),and the Temporal Experience of Pleasure Scale(TEPS).Twelve striatal subregions were selected as regions of interest(ROIs)to analyze the rsFC between each ROI and whole-brain voxels.The rsFC values of areas with significant differences were extracted for Pearson correlation analysis with negative symptoms.Results Compared with healthy controls,schizophrenia patients with PNS exhibited decreased rsFC between the right dorsal caudal putamen(DCP)and right insula,left middle frontal gyrus(MFG),right median cingulate and paracingulate gyri(MCC);between the left DCP and right putamen,left insula,left MFG;between the right dorsal rostral putamen(DRP)and bilateral MFG,left insula,right MCC;between the left DRP and right insula,left rolandic operculum;between the right ventral rostral putamen(VRP)and bilateral putamen,left MFG,right MCC;between the left VRP and right insula,left putamen,bilateral MFG,right MCC,left inferior parietal gyrus,excluding supramarginal and angular gyri.Decreased rsFC was also observed between the left ventral caudate/nucleus accumbens(inferior)and right insula,left anterior cingulate cortex,supracallosal,bilateral precuneus(a threshold of P<0.001 in voxel-level with P<0.05 in cluster-lever,corrected for family-wise error,PFWE<0.05/12=0.004).No regions showed increased rsFC in schizophrenia patients with PNS relative to healthy controls.And no significant correlations were found between striatal rsFC and negative symptoms(PBonferroni>0.05).Conclusion Schizophrenia patients with PNS exhibited widespread cortical-striatal functional connectivity abnormalities,particularly reduced rsFC between the putamen and the MFG,MCC and insula.

Objective:To explore the association between perceived social support,TMEM161B gene rs768705 polymorphism,and their interaction with incidence of depressive symptoms in the freshmen.Methods:A total of 9928 freshmen from two medical universities were investigated at baseline and follow-up two years later during 2018-2020 by cluster sampling.A self-report demographic characteristics questionnaire was used to collect information of general demographic characteristics.Perceived Social Support Scale,Beck Depression Inventory,Beck Anxiety Inventory and Adolescent Self-Rating Life Events Check List were used to measure the level of perceived social support,depressive symptoms,anxiety symptoms and the number of negative life events of individuals.Blood sam-ples were collected and typed for DNA by professionals.Results:Family support and other support were all nega-tively associated with depressive symptoms in the freshmen(OR=0.96,95％CI:0.93-0.99;OR=0.94,95％CI:0.91-0.98).There was no correlation between friend support and depressive symptoms in the freshmen(OR=0.99,95％CI:0.95-1.02).TMEM161B gene rs768705 polymorphism(AG)was positively associated with de-pressive symptoms in the freshmen(OR=1.58,95％CI:1.12-2.23).The interactions of friend support with TMEM161B gene rs768705 polymorphism(AG)(OR=1.13,95％CI:1.02-1.26)and other support with TMEM161B gene rs768705 polymorphism(AG)(OR=1.13,95％CI:1.02-1.25)had significant effects on the incidence of depressive symptoms in the females and no significant effect in the males.Conclusion:The perceived social support,TMEM161B gene rs768705 polymorphism and their interaction are associated with influence of de-pressive symptoms,and have sex difference in the freshmen.

Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

Objective To investigate the role of the GPR120 gene in the progression of sepsis,explore the molecular mechanisms through which GPR120 gene regulates NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome activation and macrophage polarization.Methods The blood and pleural fluid samples were collected from the sepsis patients and the control group.The expression of inflammatory factors and the associated proteins were detected by flow cytometry and ELISA.C57BL/6 mice and monocyte-macrophage cell line(Raw264.7)were treated with lipopolysaccharide(LPS)to construct the sepsis models.After the intervention of GPR120 agonist TUG891,the expression of GPR120 gene,NLRP3 inflammasome protein and macrophage polarization protein were detected between the control group and the sepsis group.Results The expression of inflammatory factors,such as IL-1β in the serum of septic patients,significantly increased compared with the control(P<0.001).And the expression of inflammasome proteins such as NLRP3,Caspase-1 and IL-1β in the pleural fluid also increased(all P<0.05).In vivo,LPS could induce severe inflammation in lung tissue,the GPR120 gene expression decreased in lung tissue,and inflammatory factors were up-regulated in mouse serum(P<0.01).The inflammasome-associated protein and M1 type polarization of macrophages were enhanced,the TUG891 could reduce the inflammatory response,inhibit the NLRP3 inflammasome activating,and promote the M2 polarization of macrophages(P<0.01).In vitro,LPS could inhibit the intracellular GPR120 expression.The inflammatory factors secreted more in LPS-induced sepsis cells.TUG891 could promote the up-regulation of GPR120 protein and alleviate the secretion of inflammatory factors(P<0.05).Conclusion In sepsis,GPR120 gene activation could inhibit the NLRP3 inflammasome activation,promote macrophage polarization,and reduce the inflammatory damage,thereby delay the rapid progression of sepsis.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

OBJECTIVES: To study the incidence and disease burden of congenital birth defects in children under five in China from 1990 to 2021 and to predict the incidence of congenital birth defects in this population from 2022 to 2036, providing a reference for the prevention of congenital birth defects in children. METHODS: Using the Global Burden of Disease Study 2021 (GBD 2021) database, the incidence and disability-adjusted life years (DALY) were employed to describe the disease burden. The Joinpoint regression model was used to analyze the trends in incidence and DALY rates of congenital birth defects in children under five. A grey prediction model GM(1,1) was applied to fit the trend of incidence rates of congenital birth defects in this age group and to predict the incidence from 2022 to 2036. RESULTS: In 2021, the incidence rate of congenital birth defects among children under five in China was 737.28 per 100 000. Among these, congenital musculoskeletal and limb deformities had the highest incidence rate at 307.15 per 100 000, followed by congenital heart defects (223.53 per 100 000), congenital urinary and genital tract malformations (74.99 per 100 000), and congenital gastrointestinal malformations (62.61 per 100 000). From 1990 to 2021, the incidence rate and DALY rate of congenital birth defects in children under five in China decreased at an average annual rate of 1.73% and 5.42%, respectively. The prediction analysis indicated a decreasing trend in the incidence of congenital birth defects among children under five in China from 2022 to 2036, with the incidence rate dropping from 892.36 per 100 000 in 2022 to 783.35 per 100 000 in 2036. CONCLUSIONS The incidence and disease burden of congenital birth defects in children under five in China showed a significant declining trend from 1990 to 2021. It is predicted that this incidence will continue to decrease until 2036.
Humans ; Congenital Abnormalities/epidemiology* ; China/epidemiology* ; Incidence ; Infant ; Infant, Newborn ; Child, Preschool ; Female ; Male ; Forecasting ; Disability-Adjusted Life Years