ObjectiveTo establish the mouse models of psoriasis-like lesions induced by continuous cold exposure or intermittent cold exposure combined with imiquimod （IMQ）， and to evaluate the interventional effects of Kaixuan Jiedu core prescription （KXJD） on the two models. MethodsMale C57BL/6J mice were selected and classified into two experimental batches. The first batch of 36 mice was randomized into a room temperature group， a continuous cold exposure （10 ℃/24 h） group， and an intermittent cold exposure （10 ℃/6 h） group. Each group was further divided into a normal subgroup and a model subgroup （topical application of IMQ to induce skin lesions）， with 6 mice in each subgroup， for modeling and evaluation. The second batch of 54 mice， with 6 in each group， were subjected to the same temperature grouping with an additional KXJD （30.42 g·kg^-1， continuous gavage for 5 days） group. Comprehensive evaluation of model characteristics and KXJD efficacy was conducted through Psoriasis Area and Severity Index （PASI） scoring， skin temperature measurement by infrared thermography， histopathological observation by hematoxylin-eosin （HE） staining， detection of vascular endothelial growth factor （VEGF） and platelet endothelial cell adhesion molecule 1 （CD31） by immunohistochemistry， detection of Claudin-1 and Occludin by immunofluorescence assay， determination of serum levels of tumor necrosis factor-α （TNF-α） and interleukin （IL）-10 by enzyme-linked immunosorbent assay （ELISA）， and quantification of mRNA levels of IL-17A， IL-23， IL-6， and chemokine ligand 20 （CCL20） in skin lesions by quantitative Real-time polymerase chain reaction （Real-time PCR）. ResultsModel mice in all temperature groups exhibited typical psoriasis-like skin lesions. Compared with the normal groups， the model groups showed increased PASI scores， decreased skin temperatures （P<0.05）， obvious epidermal thickening， parakeratosis， and dermal inflammatory cell infiltration， as well as elevated mRNA levels of IL-17A， IL-23， IL-6， and CCL20 （P<0.05）. Cold exposure further aggravated psoriasis. The total PASI score of the intermittent cold exposure model group was higher than that of the room temperature model group （P<0.05）. The serum IL-10 did not show a compensatory elevation， and the blood vessels presented a characteristic of elevated CD31 expression （P<0.05） without a synchronous increase in VEGF. The continuous cold exposure model group exhibited more significant dermal capillary tortuosity and dilation， with the highest mRNA levels of IL-17A， IL-23， IL-6， and CCL20 among all groups. Compared with the respective model groups， KXJD intervention alleviated skin lesions， reduced epidermal thickness and inflammatory cell infiltration， and increased skin temperature， with the temperature increase being particularly significant in the intermittent cold exposure+KXJD group （P<0.05）. Furthermore， KXJD down-regulated the expression of VEGF and CD31， restored the expression of Claudin-1 and Occludin， decreased the mRNA levels of IL-17A and IL-23 （P<0.05）， and reduced the serum TNF-α level. ConclusionThis study successfully established compound psoriasis-like mouse models induced by cold exposure combined with IMQ. It confirms that cold aggravates the severity of psoriasis by exacerbating the closure of Xuanfu （sweat pores）， microcirculation disorders， and immune imbalance. Moreover， different cold exposure patterns have distinct mechanism differences. Continuous cold exposure focuses on enhancing the inflammatory response via the IL-23/IL-17 axis and angiogenesis， simulating chronic aggravation under a long-term cold environment. Intermittent cold exposure tends to impair immune regulation and induce microvascular endothelial stress， corresponding to acute exacerbations caused by sudden temperature drops. KXJD can effectively alleviate psoriasis-like skin lesions under cold conditions by unblocking Xuanfu， regulating vasomotor function， and correcting abnormal immune-inflammatory responses.

ObjectiveTo investigate the ameliorative effects of Kaixuan Jiedu core prescription （KXJD） on skin lesions in psoriasis-like mouse models under cold environment exposure， and to analyze its influences on transient receptor potential （TRP） channels and related neuroimmune regulatory factors. MethodsThirty-six C57BL/6J mice were randomized into 6 groups， with 6 mice in each group. Two feeding conditions were set： Normal temperature and cold ［simulating a cold environment at （10±0.5） ℃， for 6 h daily］. Mice were induced to develop psoriasis-like lesions by applying imiquimod externally. The model mice were allocated into model groups and KXJD （30.42 g·kg^-1， continuous gavage for 5 days） groups. Normal mice were used as the control group. Specifically， mice were allocated into normal temperature， normal temperature model， normal temperature+KXJD， cold exposure control， cold exposure model， and cold exposure+KXJD groups. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining. The expression of cluster of differentiation （CD） 3⁺ T lymphocytes， CD11c⁺ dendritic cells （DCs）， phosphorylated extracellular signal-regulated kinase （p-ERK）， and substance P （SP） were detected by immunofluorescence assay. The protein level of transient receptor potential cation channel subfamily M member 8 （TRPM8） in the skin tissue was determined by Western blot. The expression of TRPM8， transient receptor potential cation channel subfamily V member 1 （TRPV1）， transient receptor potential cation channel subfamily A member 1 （TRPA1）， and transient receptor potential cation channel subfamily V member 2 （TRPV2） at the protein and mRNA levels was determined by immunohistochemistry and Real-time PCR， respectively. The levels of calcitonin gene-related peptide （CGRP） and neuropeptide Y （NPY） in the serum were analyzed by enzyme-linked immunosorbent assay （ELISA）. The enrichment analysis of differentially expressed genes （DEGs） and TRP pathway network construction were conducted based on the GEO database. The co-expression of TRPM8 and CGRP in the skin lesions was verified by immunofluorescence double labeling. ResultsBoth the normal temperature and cold exposure model groups showed typical psoriasis-like skin lesions. Compared with the normal temperature and cold exposure control groups， the model groups had excessive epidermal keratinization， thickened spinous layer， and inflammatory infiltration in the dermis， with increased pathological scores （P<0.05）， increased infiltration of CD3⁺ and CD11c⁺ cells and expression of p-ERK and SP， upregulated mRNA levels of TRPM8， TRPA1， and TRPV2， downregulated mRNA level of TRPV1 （P<0.05）， and reduced content of CGRP and increased content of NPY in the serum. Compared with the normal temperature and cold exposure model groups， KXJD reduced the pathological manifestations and pathological scores of psoriasis-like skin lesions （P<0.05）， and inhibited the infiltration of CD3⁺ and CD11c⁺ cells and the expression of p-ERK and SP. Gene enrichment analysis suggested that the DEGs of psoriasis were significantly enriched in the interleukin （IL）-17 signaling pathway and TRP channel inflammatory regulation. Compared with the normal temperature and cold exposure model groups， KXJD reversed the abnormal mRNA levels of genes related to the TRP channel subfamilies （P<0.05）， increased the CGRP level， and decreased the NPY level. Immunofluorescence double labeling further confirmed that compared with the model groups， KXJD down-regulated the co-expression of TRPM8 and CGRP in the skin lesions. ConclusionKXJD may ameliorate psoriasis-like skin lesions by downregulating the overexpressed cold-sensitive receptor TRPM8 in skin lesions and correcting the disorder of neuropeptide （such as SP and CGRP） release mediated by it， thereby inhibiting the IL-23/helper T cell 17 （Th17） core inflammatory pathway， suppressing the infiltration of inflammatory cells and the activation of the ERK signaling pathway， and regulating the Xuanfu （sweat pore）-TRPM8-neuroimmune response axis.

ObjectiveTo investigate the ameliorative effects and mechanisms of Kaixuan Jiedu core prescription （KXJD） on neuroimmunological inflammation in imiquimod （IMQ）-induced psoriasis-like mice. MethodsA total of 24 C57BL/6J mice were randomly divided into four groups （n=6）： Normal， model， KXJD， and tropomyosin receptor kinase A （TrkA） inhibitor GW441756 groups. The mice in the model， KXJD， and GW441756 groups were topically treated with 5% IMQ cream （62.5 mg·d^-1） on the back to induce psoriasis-like inflammation. The KXJD group received KXJD by gavage （30.42 g·kg^-1）， the GW441756 group received intraperitoneal injection of GW441756 （10 mg·kg^-1）， and the normal and model groups received an equal volume of normal saline by gavage， with continuous intervention for 5 days. The severity of skin lesions was evaluated using the psoriasis area and severity index （PASI）. Hematoxylin-eosin （HE） staining was used to measure epidermal thickness and observe pathological changes in the lesioned skin. Immunohistochemistry was employed to detect the expression of proliferating cell nuclear antigen （Ki67） and interleukin-17A （IL-17A） in the lesioned skin. Enzyme-linked immunosorbent assay （ELISA） was used to quantify the levels of interleukin-23 （IL-23） and calcitonin gene-related peptide （CGRP） in the lesioned tissues. Western blot was used to detect the expression of TrkA and phosphorylated TrkA （p-TrkA）. Immunofluorescence assay was performed to detect the expression of TrkA receptor， protein gene product 9.5 （PGP9.5）， cluster of differentiation 11c （CD11c）， and CGRP in the lesions. Flow cytometry was used to detect the activation of splenic dendritic cells （DCs）. ResultsCompared with the normal group， the model group exhibited typical psoriasis-like inflammation， characterized by erythema， infiltration and scaling， with histopathological findings of epidermal hyperkeratosis and acanthosis. The model group showed significantly increased expression of Ki67， IL-17A， IL-23 and p-TrkA （P<0.05， P<0.01）， increased fluorescence intensity of CD11c， and significantly decreased CGRP expression （P<0.05）. The splenic DC activation was significantly enhanced， as indicated by the increased mean fluorescence intensity （MFI） of CD86 （P<0.05）. Compared with the model group， both the KXJD and GW441756 groups showed amelioration of the psoriasis-like skin inflammation， with significantly down-regulated expression of IL-17A， IL-23 and p-TrkA （P<0.05， P<0.01）， significantly up-regulated expression of CGRP （P<0.01）， reduced CD11c⁺ DC infiltration， and restored splenic DC activation balance （down-regulated CD86 MFI and up-regulated CD80 and CD40 MFI）. Furthermore， the inhibitory effect of KXJD on Ki67 was significantly superior to that of the GW441756 group （P<0.01）. ConclusionKXJD may alleviate IMQ-induced psoriasis-like inflammation in mice by targeting and inhibiting TrkA receptor phosphorylation， regulating CGRP expression in the lesions， and ameliorating aberrant activation of dendritic cells， while also significantly inhibiting keratinocyte proliferation.

ObjectiveTo investigate the effects and molecular mechanisms of Kaixuan Jiedu core prescription （KXJD） on neuroinflammation and immuno-inflammation in the mouse model of imiquimod （IMQ）-induced psoriasis-like skin lesions by regulating the nerve growth factor （NGF）-tropomyosin receptor kinase A （TrkA）/transient receptor potential vanilloid 1 （TRPV1）-protease-activated receptor-2 （PAR-2） signaling pathway. MethodsA psoriasis-like skin lesion model was established in male C57BL/6J mice with IMQ. A total of 24 mice were randomized into four groups （n=6 per group）： Blank control， model， methotrexate （MTX， 1 mg·kg^-1）， and KXJD （30.42 g·kg^-1）. Immunohistochemistry was employed to detect the expression of cluster of differentiation 3 （CD3）， EGF-like module-containing mucin-like hormone receptor-like 1 （F4/80）， lymphocyte antigen 6 complex locus G （Ly-6G）， substance P （SP）， calcitonin gene-related peptide （CGRP）， NGF， phosphorylated TrkA （p-TrkA）， phosphorylated TRPV1 （p-TRPV1）， and PAR-2 in skin lesions. Serum levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23） were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence assay and Western blot were employed to determine the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65）. Reverse transcription quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and C-X-C motif chemokine ligand 1 （CXCL1） in skin lesions. Correlation analysis was performed. ResultsCompared with the blank control group， the model group showed increased positive areas of CD3⁺， F4/80⁺， and Ly-6G⁺ in skin lesions （P<0.05）， elevated serum levels of IL-17A and IL-23 （P<0.05）， increased positive areas of SP and CGRP in skin lesions （P<0.05）， increased positive areas of NGF， p-TrkA， p-TRPV1， and PAR-2 （P<0.05）， elevated ratios of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.05）， and upregulated mRNA levels of IL-1β， TNF， IL-6， and CXCL1 （P<0.05）. Compared with those in the model group， all the above indicators were reversed in the KXJD group （P<0.05）. MTX only downregulated the expression of p-TRPV1 and PAR-2 （P<0.05）， with no significant effects on the expression of NGF， p-TrkA， or CGRP. ConclusionKXJD inhibits the NGF-TrkA/TRPV1-PAR-2 signaling pathway to reduce neuropeptide release and simultaneously downregulates the p38 MAPK/NF-κB signaling pathway and the expression of downstream pro-inflammatory factors to ameliorate psoriasis-like neuroinflammation and immuno-inflammation. The therapeutic effect of KXJD on psoriasis-like inflammation is closely associated with the inhibition of the NGF-TrkA/TRPV1-PAR-2 signaling pathway. This study provides experimental evidence for the modern interpretation of the Xuanfu theory.

The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

Aim To explore the material basis and un-derlying mechanism of Qingre Huoxue Formula(QRHXF)in the treatment of non-small cell lung cancer(NSCLC)by applying network pharmacology,molecular docking technology and bioinformatics com-bined with animal experiments.Methods TCMSP,ECTM,and BATMAN databases were used to obtain active components and corresponding targets of QRHXF;GEO and DisGeNENT databases were con-ducted to acquire NSCLC-associated differential expres-sion genes.By intersecting them,the common targets were obtained.It was chosen to construct a herb-com-ponent-disease network and protein-protein interaction(PPI)network.Furthermore,DAVID database was used to perform gene ontology(GO)function and Kyo-to encyclopedia of genes and genomes(KEGG)path-way enrichment analyses.The molecular docking was presented by adopting Autodock Vina program to verify key targets.RNA-seq datawere downloaded from TC-GA database to obtain differential gene expression.Ka-planMeier(KM)analysis was performed to analyze the relationship between gene expression and overall sur-vival.Mouse subcutaneous tumor model of LLC was established.The effects of QRHXF on body weight,tumor volume and weight were monitored for pharmaco-dynamic analysis.Tumor tissues slides were stained with hematoxylin and eosin(HE)for histopathological examination.Immunohistochemistry(IHC)staining was employed for detecting Ki67 and EP300.Western blot was performed to measure the protein expression of TP53,CDK1 and NTRK1.Results The results of net-work pharmacology showed that a total of seven com-mon targets were screened from NSCLC and QRHXF,and the effect of QRHXF on anti-NSCLC may occur via multiple signaling pathways,including cell cycle.The results of molecular docking indicated that the main ac-tive components of QRHXF had low binding energy and stable docking conformation with the molecular target for treating NSCLC.According to bioinformatic analy-sis,there were significant differences in BRCA1,CDK1 and NTRK1 mRNA expression between tumor tissues and normal tissues,which were also prognostic factors for overall survival.Animal experimental research showed QRHXF inhibited subcutaneous tumor growth(P＜0.01)and improved the quality of life in mice with NSCLC.After QRHXF intervention,the density of tumor cells was significantly reduced,and necrotic are-as were increased.The expressions of Ki67 and EP300 were significantly decreased.Compared with the model group,Western blot showed up-regulation of TP53 and NTRKA(P＜0.05),whereas CDK1 were down-regu-lated(P＜0.05).Conclusion QRHXF exerted anti-NSCLC effects by regulating NTRK1,EP300,TP53,CDK1 and inducing cell cycle,cell cycle arrest and in-hibiting tumor growth,metastasis and angiogenesis.

Objective To explore the clinical efficacy of transcranial combined peripheral magnetic stimu-lation on bladder and voiding ability in patients with NB after spinal cord injury.Methods From September 2023 to October 2024,60 patients with NB after spinal cord injury were chosen from the Department of Rehabilitation Medicine of the First Affiliated Hospital of Bengbu Medical University,and were separated into the regular group(n=15),M1 area stimulation group(n=15),sacral nerve root stimulation group(n=15),and combined stimulation group(n=15).The control group underwent conventional rehabilitation treatment,the M1 area stimu-lation group added repetitive transcranial magnetic stimulation(rTMS)of the M1 area of the motor cortex,the sacral nerve root stimulation group added repetitive peripheral magnetic stimulation(rPMS)of the sacral 3 nerve roots,and the co-stimulation group added rTMS of the M1 area and rPMS of the sacral 3 nerve roots,and the treat-ment was carried out for 4 weeks in total.Urodynamic indices,voiding diaries,and neurogenic bladder symptom scores(NBSS)were assessed before and after therapy in the four groups.Results Before therapy,the differences in maximum bladder capacity,bladder capacity at the time of the first urge to urinate,maximum urine flow rate,residual urine volume,average number of urination per day,average daily urinary output,and NBSS scores of the four groups were not statistically significant when compared with those of the pre-treatment group(P<0.05);after treatment,the maximum bladder capacity,bladder capacity at the time of the first urge to urinate,maximum urine flow rate,residual urine volume,average number of urination per day,average daily urinary output,and NBSS scores were all improved compared with those before treatment(P<0.05);in comparison between the groups,after treatment,the Urodynamic indices,voiding diaries,and NBSS scores of the combined group were better than those of the other three groups(P<0.05).Conclusion Transcranial combined peripheral bidirectional feedback magnetic stimulation therapy can improve urodynamic and voiding symptoms and promote the recovery of bladder and voiding function in patients with NB after spinal cord injury

Objective:To comprehensively evaluate the cost and cost-effectiveness of the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, and provide reference for optimizing colorectal cancer screening strategies.Methods:Based on the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, parameters such as initial screening positivity rates, colonoscopy compliance rates, and detection rates for colorectal-related lesions among residents aged 50-74 were obtained. Questionnaire surveys assessed program costs and direct medical costs associated with colorectal cancer-related lesions. From a health system perspective, the cost-effectiveness ratio was calculated using the Early Detection Cost Index (EDCI) and the cost per detected case, followed by sensitivity analysis.Results:A total of 5 881 364 screenings were completed from 2020 to 2022. The initial screening positive rate (positive for either questionnaire or fecal immunochemical testing ) was 16.83%, with a colonoscopy compliance rates of 33.96% ( n=336 150). Detection rates for non-advanced adenomas, advanced adenomas, and colorectal cancer were 24.83% ( n=83 453), 11.91% ( n=40 033), and 1.01% ( n=3 397), respectively. Initial screening positivity rates and detection rates increased with age, while colonoscopy compliance rates decreased with age. Cost analysis showed a total project investment of 378 730 457 yuan, with initial screening costing 146 633 103 yuan (38.72%) and diagnostic colonoscopy 232 097 354 yuan (61.28%). The average cost per initial screening and diagnostic colonoscopy was 24.93 and 690.46 yuan, respectively. Direct medical costs for non-advanced adenomas, advanced adenomas, and colorectal cancer at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ were 4 921, 8 380, 42 547, 62 156, 66 720, and 72 334 yuan, respectively. Cost-effectiveness analysis indicated that screening needed to detect one case of colorectal cancer required 1 731 people and cost 111 490 yuan; the cost per detected advanced adenoma was 9 460 yuan, and the EDCI was 0.09. Costs decreased with increasing age per detected colorectal lesion. Sensitivity analysis showed that increasing colonoscopy compliance could reduce the cost-effectiveness ratio. Conclusions:The colorectal cancer screening program for key populations in Zhejiang Province demonstrates cost-effectiveness. Improving colonoscopy compliance can enhance overall screening effectiveness and economic benefits.

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 explore the distribution patterns of traditional Chinese medicine(TCM)syndromes in patients with metabolic syndrome caused by antipsychotic drugs.Methods A standardized TCM syndrome survey was performed to collect diagnostic information from 160 patients diagnosed with metabolic syndrome due to antipsychotic drug use.Subsequent frequency analysis,cluster analysis,and Bayesian network analysis were carried out.The syndrome pattern distribution was ultimately determined through relevant literatures and expert opinions.Results Five TCM syndromes were identified through frequency,cluster,and Bayesian network analyses.The most common syndrome was qi deficiency with phlegm-dampness(30％),followed by spleen deficiency with phlegm-Heat(23.75％),qi and yin deficiency Pattern(21.88％),yin deficiency with damp-heat(17.50％),and stomach fire hyperactivity pattern(6.88％).Conclusion The pathogenesis of antipsychotics-induced metabolic syndrome involves a complex interplay of deficiency and excess factors.The primary disease is mainly located at the spleen and stomach,with involvement of the liver,kidney,and heart.Pathogenic factors include qi deficiency,yin deficiency,dampness,heat,pathogenic fire,and phlegm.