ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

In this paper， by consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing， and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified， in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research， musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name， but there were also aliases such as Shefu， Xiangzhang and Xiangqizi. In ancient times， Moschus berezovskii， M. sifanicus and M. moschiferus were the main sources of Moschus， and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times， Moschus of M. moschiferus produced in northeast China， M. sifanicus produced in Gansu， Sichuan and other places， and M. berezovskii produced in Ningxia， Shaanxi and other places are regarded as genuine. In ancient times， gunshots， lassoes， arrow shots and other methods were generally used to hunt live musk deer， and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo， and dried in the shade after harvesting， which was known as Maoke Shexiang. Cut open the sachet， remove the shell and dry preservation， commonly known as Moschus kernel. In modern times， the method of taking Moschus from the living body of cultured musk deer is adopted， that is， Moschus kernel is directly taken from its sachet， dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources， but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year， and before the next summer， it is better to gather sachet in winter. In recent times， it is believed that the shell Moschus is dry， full， thin， elastic， loose inside， many particles， strong and persistent aroma for the best， while the Moschus kernel is particle purple-black， powder yellow-brown， soft and oily texture， strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities， it is ground and used as medicine. Because its composition is not suitable for heating， the processing method is most common in preparations such as grinding into powder and putting into pills or powders， which has the effect of opening up the orifices and refreshing the mind， and it has continued to this day. Based on the research conclusions， it is suggested that the development of famous classical formulas containing Moschus， M. sifanicus， M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula， it should be processed and used as medicine， while those without processing requirements should be used as raw products.

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

OBJECTIVE: To develop a method for identifying high-risk patients among septic populations requiring mechanical ventilation, and to conduct phenotypic analysis based on this method. METHODS: Data from four sources were utilized: the Medical Information Mart for Intensive Care (MIMIC-IV 2.0, MIMIC-III 1.4), the Philips eICU-Collaborative Research Database 2.0 (eICU-CRD 2.0), and the Anhui Medical University Second Affiliated Hospital dataset. The adult patients in intensive care unit (ICU) who met Sepsis-3 and received invasive mechanical ventilation (IMV) on the first day of first admission were enrolled. The MIMIC-IV dataset with the highest data integrity was divided into a training set and a test set at a 6:1 ratio, while the remaining datasets were served as validation sets. The demographic information, comorbidities, laboratory indicators, commonly used ICU scores, and treatment measures of patients were extracted. Clinical data collected within first day of ICU admission were used to calculate the sequential organ failure assessment (SOFA) score. K-means clustering was applied to cluster SOFA score components, and the sum of squared errors (SSE) and Davies-Bouldin index (DBI) were used to determine the optimal number of disease subtypes. For clustering results, normalized methods were employed to compare baseline characteristics by visualization, and Kaplan-Meier curves were used to analyze clinical outcomes across phenotypes. RESULTS: This study enrolled patients from MIMIC-IV dataset (n = 11 166), MIMIC-III dataset (n = 4 821), eICU-CRD dataset (n = 6 624), and a local dataset (n = 110), with the four datasets showing similar median ages and male proportions exceeding 50%; using 85% of the MIMIC-IV dataset as the training set, 15% as the test set, and the rest dataset as the validation set. K-means clustering based on the six-item SOFA score was performed to determine the optimal number of clusters as 3, and patients were finally classified into three phenotypes. In the training set, compared with the patients with phenotype II and phenotype III, those with phenotype I had the more severe circulatory and respiratory dysfunction, a higher proportion of vasoactive drug usage, more obvious metabolic acidosis and hypoxia, and a higher incidence of congestive heart failure. The patients with phenotype II was dominated by respiratory dysfunction with higher visceral injury. The patients with phenotype III had relatively stable organ function. The above characteristics were consistent in both the test and validation sets. Analysis of infection-related indicators showed that the patients with phenotype I had the highest SOFA score within 7 days after ICU admission, initial decreases and later increases in platelet count (PLT), and higher counts of neutrophils, lymphocytes, and monocytes as compared with those with phenotype II and phenotype III, their blood cultures had a higher positivity rates for Gram-positive bacteria, Gram-negative bacteria and fungi as compared with those with phenotype II and phenotype III. The Kaplan-Meier curve indicated that in the training, test, and validation sets, the 28-day cumulative mortality of patients with phenotype I was significantly higher than that of patients with phenotypes II and phenotype III. CONCLUSIONS Three distinct phenotypes in septic patients receiving IMV based on unsupervised machine learning is derived, among which phenotype I, characterized by cardiorespiratory failure, can be used for the early identification of high-risk patients in this population. Moreover, this population is more prone to bloodstream infections, posing a high risk and having a poor prognosis.
Humans ; Machine Learning ; Sepsis/therapy* ; Respiration, Artificial ; Intensive Care Units ; Organ Dysfunction Scores ; Male ; Female ; Middle Aged ; Adult

Humans ; Prognosis ; Treatment Outcome ; Pulmonary Disease, Chronic Obstructive

Objective To establish the rapid identification method of Hedysari Radix wild and cultivated products by integrating the identification characteristics of TCM traits obtained by intelligent senses such as electronic nose and colorimeter based on the multivariate statistical analysis method;To provide new ideas and methods for the formulation of commodity specification standards and the application research of market quality control for Hedysari Radix.Methods Totally 29 batches of samples of Hedysari Radix were detected based on colorimeter and electronic nose technology to obtain their sensory information,and the effective components of Hedysari Radix were determined by high performance liquid chromatography(HPLC)and other methods for joint analysis.After establishing the optimal experimental conditions of Hedysari Radix electronic nose,multivariate statistical analysis methods,such as principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA)and clustering analysis,were used to establish the identification model of Hedysari Radix wild and cultivated commodities.Results The optimum test conditions of Hedysari Radix electronic nose(particle size of 65 mesh):the sample weight was 2.0 g,the optimum temperature of the sample was 50℃,and the time was 25 min.A single intelligent sensory result could not quickly and accurately identify the two,but the fusion information could quickly identify the wild and cultivated commodities of Hedysari Radix,and the chemical composition had a certain correlation with the color and taste.Conclusion Electronic nose and colorimeter can quickly and accurately distinguish wild and cultivated Hedysari Radix after multivariate statistical analysis,which is simple and feasible.The combined analysis of its related properties and active components can be used for the quality evaluation of Hedysari Radix.

Ankylosing spondylitis(AS)is a typical spinal arthritis characterised by inflammatory back pain,which seriously affects the health and quality of life of patients.The clinical efficacy of Chinese medicine in the treatment of ankylosing spondylitis is clear,but the mechanism is not clear,and the existing animal models cannot be well applied to the evaluation of Chinese medicine in the treatment of ankylosing spondylitis.Therefore,this paper summarizes the existing animal models based on Chinese and Western medicine clinical diagnosis,disease characteristics,etiology and Chinese medicine evidence,and finds that among the existing animal models,the proteoglycan-induced arthritis mouse model has a higher Chinese and Western medicine clinical fit than the other models,but lacks the corresponding Chinese medicine evidence model evaluation.The other animal models had a higher Western clinical match,but lacked the characteristics of the Traditional Chinee Medicine(TCM)syndrome.As ankylosing spondylitis is a chronic inflammatory autoimmune disease with complex pathogenic factors,the existing animal models cannot better simulate the clinical symptoms.Therefore,the establishment of animal models of ankylosing spondylitis with the characteristics of Chinese and Western clinical evidence is a future research priority for AS TCM.

Objective:To explore the application effect of multi-sensory stimulation with breastmilk in preterm infants with venipuncture pain, so as to provide theoretical guidance for clinical implementation of neonatal pain management.Methods:This study was a randomised controlled trial that selected 90 cases of preterm infants who were admitted to the Department of Neonatal Internal Medicine of Shanxi Children′s Hospital from May to October 2023, and were randomly divided into the control group and the intervention group, with 45 cases in each group. The control group received routine neonatal analgesia based on preparation before intervention, and the intervention group received multi-sensory stimulation with breastmilk based on preparation before intervention. Premature Infant Pain Profile-Revised(PIPP-R), The Chinese COMFORTneo Scale and physiological stress indicators (heart rate and oxygen saturation) were used to compare the pain level, comfort level and physiological stress response of preterm infants in the two groups 3 min before, during and 1 to 5 min after the venipuncture operation.Results:Finally, 80 cases of preterm infants were included with 40 cases in each group. The control group was born at a gestational age of (34.61 ± 1.16) weeks, with 19 males and 21 females; the intervention group was born at a gestational age of (34.74 ± 1.16) weeks, with 22 males and 18 females. Comparison between the groups showed that during and 5 min after the operation, the PIPP-R scale scores of the intervention group were (6.83 ± 0.26), (0.80 ± 0.25) points, respectively, which were lower than those of the control group (12.25 ± 0.70), (2.83 ± 0.36) points, and the differences were statistically significant (Wald χ2=53.31, 21.43, both P<0.01).The Chinese COMFORTneo Scale scores of the intervention group were (14.15 ± 0.64), (6.45 ± 0.13) points, which were lower than those of the control group (20.87 ± 0.82), (8.20 ± 0.32) points, and the differences were statistically significant (Wald χ2=41.89 and 25.75, both P<0.01); the heart rate of the intervention group were (161.07 ± 1.09), (142.48 ± 0.99) beats/min, which were lower than those of the control group(169.30 ± 1.93), (147.23 ± 2.15) beats/min, and the differences were statistically significant (Wald χ2=13.83, 4.03, both P<0.05). During the operation to 2 min after the operation, the blood oxygen saturation of the intervention group were 0.950 3 ± 0.004 0, 0.959 3 ± 0.003 4, 0.9663 ± 0.003 0, respectively, which were higher than those of the control group 0.925 3 ± 0.003 6, 0.940 5 ± 0.003 6, 0.9500 ± 0.004 3, and the differences were statistically significant (Wald χ2=21.98, 14.62, 9.70, all P<0.05). Conclusions:Multi-sensory stimulation with breastmilk can reduce the pain degree in preterm infants, improve the comfort level of preterm infants, reduce the physiological stress response and promote physiological stability of preterm infants during and after the operation of venipuncture.

Rheumatoid arthritis(RA)is an autoimmune disease with the basic pathological manifestation of synovial inflammation.Symmetric poly-articular pain and swelling are the main symptoms in clinical practice,and even extra-articular manifestations and comorbidities such as interstitial fibrosis and coronary artery disease are triggered,which seriously affect the quality of life of patients.Traditional Chinese medicine(TCM)has achieved good clinical efficacy in the prevention and treatment of RA with the advantages of multi-pathway,multi-target,multi-component,and less toxic side effects,and plays an important role in the treatment of RA.Recently,many studies have demonstrated that Chinese medicine monomers and Chinese herbal compound can control inflammation,reduce angiogenesis,induce apoptosis of synovial fibroblasts,and inhibit their proliferation,invasion and migration by regulating the PI3K/Akt signaling pathway,so as to play a key role in the treatment of RA.For this reason,the article summarizes current knowledge regarding the PI3K/Akt signaling pathway and its role in RA,as well as summarizes the current research progress of TCM in the treatment of RA by regulating the PI3K/Akt signaling pathway.The aim of this review is to provide theoretical bases for the prevention and treatment of RA and the development of new drugs.

Ankylosing spondylitis(AS)is a chronic inflammatory autoimmune disease characterized by inflammatory back pain.Its pathological features mainly include inflammation,bone destruction,and pathologic new bone formation.The etiology of AS is complex,and it may be related to genetics,infections,the environment,and intestinal flora.Its pathogenesis has not yet been clarified.In recent years,osteoimmunology,as a new theme in the study of inflammatory arthritis,plays an important role in the pathogenesis and development of AS,which was embodied in the inflammatory response and imbalance of bone metabolism.Traditional Chinese medicine(TCM)has the characteristics of multiple pathways,multiple components,multiple targets and multiple levels.TCM can improve the inflammatory response and bone metabolism imbalance of AS by regulating the osteoblasts of the skeletal system and the related factors of the immune system,thus to prevent and control AS.For this reason,the paper summarizes the role of bone immunology in the pathogenesis of AS,and reviews the current status of research on the intervention of TCM in bone immunology for the treatment of AS,with a view to providing certain references for the future clinical application of TCM in the prevention and treatment of AS.