Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

Artificial intelligence (AI) technology enhances the function of acupuncture clinical decision support system (CDSS) by promoting the accuracy of its diagnosis, assisting the formulation of personalized therapeutic regimen, and realizing the scientific and precise evaluation of its therapeutic effect. This paper deeply analyzes the unique advantages of AI-based acupuncture CDSS, including the intelligence and high efficiency. Besides, it points out the challenges of data security, the lack of model interpretation and the complexity of interdisciplinary cooperation in the development of acupuncture CDSS. With the continuous development and improvement of AI technology, acupuncture CDSS is expected to play a more important role in the fields of personalized medicine, telemedicine and disease prevention, and to further advance the efficiency and effect of acupuncture treatment, drive the modernization of acupuncture, and enhance its position and influence in the global healthcare system.
Humans ; Acupuncture Therapy ; Artificial Intelligence ; Decision Support Systems, Clinical

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.
Humans ; Inflammatory Bowel Diseases/therapy*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

Objective To study the clinical characteristics and medication patterns of Wangbi Tablets in treating patients with knee osteoarthritis(KOA)in the real world and to analyze the advantages and specific features of Chinese patent medicines in treating advantage disease.Methods A prospective case registry study was conducted,registering 3 000 patients from 30 TCM and Western medicine hospitals across China from April 2019 to December 2021.Data on gender,age,BMI,Chinese medicine staging(CMS),K-L grading,medication duration,VAS score,medical history and combined medication were collected for descriptive analysis.Comparisons were made between different stages and between single-use and combined-use groups.The Apriori algorithm was used for association analysis of combined medications.Results A total of 2 999 patients were included,with 2 063 females(68.79%)and 936 males(31.21%).The average age was(56.89±8.90)years.The average BMI was(23.80±2.88)kg/m2.The proportion of patients in CMS I was 512(17.07%),with a VAS median score of 8,while the proportion of patients in CMS Ⅱ was 2 181(72.73%),with a VAS median score of 6.The proportion of patients in CMS Ⅲ was 306(10.20%),with a VAS median score of 3;316 cases(10.54%)were classified as K-L grade I,2 477 cases(82.59%)as grade Ⅱ,204 cases(6.80%)as grade Ⅲ,and 2 cases(0.07%)as grade Ⅳ.Medication analysis indicated that the single-use group(1507 cases,50.25%)was larger than the combined-use group(1 492 cases,49.75%).In terms of the number of drugs used in combination,one(39.01%)and two(38.14%)were the main types;in terms of medication types,combination therapy with Western medicine(62.27%)and simultaneous use of Western medicine and other Chinese materia medica(26.14%)were the main methods;the top three drugs with the highest frequency of combination use were glucosamine capsules,imrecoxib tablets and sodium hyaluronate injection.The top three drug combinations with the highest support were"Huoxue Zhishang Powder+imrecoxib tablets","glucosamine capsules+imrecoxib tablets"and"glucosamine capsules+sodium hyaluronate injection".Inter-group comparisons showed that the medication duration for Wangbi Tablets in CMS I was longer than in CMS Ⅱ and CMS Ⅲ(P<0.01).The proportion of patients on monotherapy in CMS I(62.11%)was higher than in CMS Ⅱ(46.54%)and CMS Ⅲ(56.86%)(P<0.001).Among patients in CMS I(16.41%)and CMS Ⅲ(21.24%),the highest proportion used one combined medication,whereas in CMS Ⅱ,the highest proportion was for those using two combined medications(20.50%).In all three groups,CMS I(19.53%),CMS Ⅱ(33.70%)and CMS Ⅲ(30.72%),the highest proportion of combined medications was Western medicine.Conclusion More than half of the patients treated KOA with Wangbi Tablets alone.Approximately one-fifth of the patients were in CMS I,with a median pain score of 8.The average duration of medication for patients in CMS I,CMS Ⅱ and CMS Ⅲ decreases,and there is no obvious pattern in the medication method at different stages;combination therapy is represented by"Huoxue Zhishang Powder+imrecoxib tablets"and"glucosamine capsules+imrecoxib tablets".

Objective:To investigate the situation of computed tomography(CT)equipment and socio economic development of various grades and classifications of medical institutions in Jiangsu Province,and to analyze the interrelationship between them.Methods:From October 20,2023 to November 20,2023,a questionnaire survey was conducted on imported and domestic CT equipment of various grades and classifications of medical institutions in 13 prefecture-level cities in Jiangsu Province through online questionnaire survey of"questionnaire star".The gross domestic product(GDP)of each prefecture-level city in Jiangsu province was used as an indicator of measuring the level of socio-economic development in the region.The CT number,the row number of detector,quality of image,the total examination case number of daily average and the daily average case number of single machine examination of medical institutions of various grades and classifications of 13 prefecture-level cities were used to conduct correlation analysis with GDP values of various districts.Results:A total of 910 questionnaires were distributed,and 512 questionnaires were retrieved.There were 482 valid questionnaires in the 512 questionnaires,and the valid rate was 94.15,which involved to 482 various grade and classification institutions of 13 prefecture-level cities in Jiangsu province.The number of imported and domestic CT equipment in the 13 prefecture-level cities of Jiangsu Province positively correlated with the GDP of each city(r=0.882,0.880,P<0.001).The number of imported CT equipment with 64 rows and more than 64 rows,and with less than 64 rows,and the number of domestic CT equipment with 64 rows and more than 64 rows,and with less than 64 rows all positively correlated with the GDP of each city(r=0.880,0.881,0.736,0.897,P<0.05).The total number of daily average of examinations for imported and domestic CT equipment of 13 prefecture-level cities positively correlated with the GDP of each city(r=0.774,0.814,P<0.05).There were no significant difference in the image quality and the daily average case number of single machine examination between the domestic CT equipment and the imported CT equipment(P>0.05).Conclusion:The medical institutions of city with high level of economic development have more quantitative and more high-end CT equipment,and the quality of image of domestic CT equipment is equal to that of imported CT equipment regardless of the high and low level of economic development.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.