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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective:To analyze the changes and structural variations in hospitalization costs for patients with lung malignancies after the implementation of diagnosis-intervention packet (DIP) payment system, and to evaluate its effectiveness.Methods:Data from the first page of medical records and hospitalization cost data from the hospital information system of a tertiary general hospital in Henan Province were extracted for patients diagnosed with lung malignancies from 2020 to 2023. The data were divided into pre-implementation group (2020—2021) and post-implementation group (2022—2023) based on the implementation time of DIP. Chi-square test, t test, and Wilcoxon rank-sum test were used to analyze the differences in basic characteristics and hospitalization costs of patients with lung malignancies before and after the implementation of DIP. Grey relational analysis was employed to examine the internal associations between total hospitalization costs and various cost components. Structural variation analysis was used to assess the changes in the structure of hospitalization costs after the implementation of DIP. Results:A total of 14 587 hospitalized patients with lung malignancies were included, with 6 807 cases in the pre-implementation group and 7 780 cases in the post-implementation group. The average length of hospital stay decreased from (13.17±6.74) days before implementation to (12.02±6.49) days after implementation ( P<0.05). The proportion of level-four surgeries increased from 46.4% to 57.0% ( P<0.05). The average hospitalization cost per patient with lung malignancies decreased from 56 952 yuan before DIP implementation to 55 560 yuan after implementation ( P<0.05). For patients with lung malignancies diagnosed as C34.1, C34.2, C34.3, and C34.8, the top four cost components most strongly associated with total hospitalization costs were treatment costs, material costs, comprehensive medical service costs, and diagnostic costs, with correlation coefficients all>0.80. For patients with C34.9, the top four cost components most strongly associated with total hospitalization costs were treatment costs, comprehensive medical service costs, diagnostic costs, and Western medicine costs, with correlation coefficients>0.95. For patients diagnosed as C34.1, C34.2, C34.3, and C34.9, diagnostic costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 75%, among which Western medicine costs and material costs showed negative variation. For patients diagnosed as C34.8, treatment costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 80%, among which Western medicine costs showed negative variation. Conclusions:The implementation of DIP reduced the hospitalization costs for patients with lung malignancies, optimized the structure of hospitalization costs, improved the efficiency of medical services, and promoted the rational allocation of medical resources.

Polygonatum sibiricum polysaccharide(PSP)is a polysaccharide with multiple pharma-cological activities that has been widely studied and used in the human body.However,there is cur-rently a lack of research investigating the potential advantages of PSP in poultry farming.This study investigated the effects of adding PSP to drinking water on the growth performance,antioxi-dant status,serum biochemical indicators,ileal tissue morphology,immune organs,and intestinal function of chicks.88 Hailan brown laying hens were randomly divided into 4 groups,with 22 hens in each group,namely the blank control group(CON),and fed with basic feed;The low-dose PSP group(250 mg/L),the medium dose PSP group(500 mg/L),and the high-dose PSP group(1 000 mg/L)were fed with corresponding doses of PSP through drinking water on the basis of basic feed,and the experimental period was 21 d.The initial and final body weight and immune or-gan relative quality of chicks,serum biochemical indicators,the activities of SOD,CAT,and GSH-Px,as well as the contents of T-AOC and MDA in the serum of chicks were measured;HE stai-ning method was used to observe the pathological changes of intestinal tissue slices in the ileum;Real time fluorescence quantitative PCR technology was used to detect the mRNA expression lev-els of cytokines ZO-1,Claudin-1,Occludin,Mucin-2,IL-1β,TNF-a,IFN-γ,IL-4,IL-8,and IL-10 in the ileum.The results showed that compared with the blank control group,the addition of medium dose PSP significantly increased the final relative quality(P＜0.01),the final body weight and ADG of PSP500 group chicks significantly increased(P＜0.01),and the F/G of PSP250 and PSP500 groups significantly decreased(P＜0.05 or P＜0.01).The villus height of the jejunum in the 200,500,and 1 000 mg/L PSP groups of chicks significantly increased(P＜0.05).The SOD ac-tivity significantly increased(P＜0.01),and the CAT activity in the PSP1000 group significantly increased(P＜0.01).The PSP500 and PSP1000 groups significantly reduced the mRNA expression of cytokines IL-1β,IL-4,and IFN-γ in the ileum(P＞0.05);PSP did not show significant changes in serum total protein(TP),albumin(ALB),glucose(GLU),cholesterol(T-CHO)content,and immune organ index(P＜0.05).In summary,PSP can improve growth performance,enhance an-tioxidant capacity,improve ileal morphology and epithelial barrier function,and regulate mucosal immune status.Considering the overall economic benefits,the recommended level of PSP addition is 500 mg/L.

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

Objective To conduct a visual analysis of research hotspots and development trends in stress ulcer(SU)from 2004 to 2024 using CiteSpace software.Methods Relevant SU literature published between January 1,2004,and May 7,2024,was retrieved from the Web of Science data-base and analyzed visually using CiteSpace software.Results A total of 623 articles were included in this study.The number of publications followed a wavy increase trend from 2004 to 2024.The au-thor with the highest number of publications was MOLLER M H,the institution with the most publica-tions was Copenhagen University Hospital in Denmark,and the country with the most publications was China.Keyword analysis revealed that SU research primarily focused on exploring pathogenesis and developing prophylactic and therapeutic drugs.Conclusion The pathogenesis of SU needs further elucidation.Research on drugs and prevention tailored to different mechanisms inducing SU,the im-pact of enteral nutrition on patient prognosis,and the effectiveness of traditional Chinese medicine in prevention and treatment are hotspots and development trends in future research.

Objective: To investigate the mechanism of Anemoside B4 (AB4) on glutamine metabolism in oral li- chen planus (OLP) epithelial cells via the nitric oxide synthase 3 (NOS3)-dihydrofolate reductase (DHFR) axis . Methods: Bioinformatics analysis was performed to identify the intersection of molecular targets of OLP , AB4 , and genes related to glutamine metabolism . A lipopolysaccharide ( LPS)-induced HOK-16B model of OLP was estab- lished . HOK-16B were divided into Ctrl group , OLP group , AB4 group , OLP + oe-NOS3 group , OLP + sh-NOS3 group , OLP + sh-NOS3 + oe-DHFR group , and OLP + sh-NOS3 + AB4 group . Cell proliferation was detected by cell counting kit-8 (CCK-8) ; cell apoptosis was detected by TdT-mediated dUTP Nick-End Labeling ( TUNEL) ; inflammatory factors iInterleukin (IL)-1β, tumor necrosis factors-α ( TNF-α) concentrations in cell supernatants were measured using enzyme-linked immunosorbent assay (ELISA) kits; glutamine uptake and glutamate produc- tion were determined using kits; and the protein expression of alanine-serine-cysteine transporter2 ( ASCT2) and glutamine synthase (GLS) was assessed by Western blot. Results: Bioinformatics analysis of molecular targets of OLP , AB4 , and genes related to glutamine metabolism revealed three intersection targets : NFE2L2 , NOS1 , and NOS3 . Compared with the Ctrl group , the OLP group exhibited decreased HOK-16B cell viability (P < 0. 001) , increased apoptosis rate (P < 0. 01) , upregulated concentrations of IL-1βand TNF-α(P < 0. 001) , elevated glu- tamine uptake and glutamate production (P < 0. 01) , and enhanced expression of ASCPT2 and GLS proteins (P < 0. 001) . Compared with the OLP group , the AB4 group showed improved cell viability (P < 0. 05) , reduced apop- tosis rate and release of IL-1βand TNF-α(P < 0. 05) , decreased glutamine uptake and glutamate production (P < 0. 05) , and downregulated expression of ASCPT2 and GLS proteins ( P < 0. 001) . Compared with the OLP group , the OLP + oe-NOS3 group had increased HOK-16B cell viability (P < 0. 01) , reduced apoptosis rate (P < 0. 05) , decreased concentrations of IL-1βand TNF-α(P < 0. 05) , lowered glutamine uptake and glutamate pro- duction (P < 0. 05) , and weakened expression of ASCPT2 and GLS proteins (P < 0. 01) ; whereas the OLP + sh- NOS3 group had decreased HOK-16B cell viability ( P < 0. 05) , increased apoptosis rate ( P < 0. 05) , elevated concentrations of IL-1βand TNF-α ( P < 0. 01 ) , increased glutamine uptake and glutamate production ( P < 0. 05) , and enhanced expression of ASCPT2 and GLS proteins (P < 0. 001) . Compared with the OLP + sh-NOS3 group , both the OLP + sh-NOS3 + oe-DHFR group and the OLP + sh-NOS3 + AB4 group showed increased HOK- 16B cell viability (P < 0. 001) , reduced apoptosis rate (P < 0. 05) , decreased concentrations of IL-1βand TNF-α (P < 0. 01) , lowered glutamine uptake and glutamate production ( P < 0. 05) , and weakened expression of AS- CPT2 and GLS proteins ( P < 0. 05) . Conclusion AB4 inhibits the progression of OLP by mediating glutamine metabolism via the regulation of the NOS3-DHFR axis .

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Compared with total knee arthroplasty, unicondylar knee replacement has the advantage of preserving the knee tissue structure and motor function to the greatest extent. Pre-clinical in-vitro test is an important tool to evaluate the safety and effectiveness of unicondylar knee prostheses, and it is also a key focus of the product registration process. Through collection, comparison, and analysis of current regulations, technical standards, guidelines, and related research literature, this paper expounds on the relevant research methods for the pre-clinical in-vitrotesting of unicondylar knee prostheses. At the same time, in conjunction with current evaluation requirements and experience, the study discusses the focus of pre-clinical performance research for unicondylar knee prostheses during the registration process to clarify the performance evaluation requirements of this product category. This aims to provide a reference for the pre-clinical performance research of unicondylar knee prostheses and to standardize industry testing standards.
Knee Prosthesis ; Arthroplasty, Replacement, Knee ; Humans ; Prosthesis Design ; Materials Testing