ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis （KOA） with cold-dampness obstruction syndrome， and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group， a treadmill plus climate chamber group， an anterior cruciate ligament transection （ACLT） plus climate chamber group， an ACLT group， a destabilization of the medial meniscus （DMM） plus climate chamber group， a DMM group， an intra-articular injection plus climate chamber group， and an intra-articular injection group， with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model， while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee， and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate （MIA） into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber （relative humidity 60%， temperature 4 ℃， wind speed 6 m/s） simultaneously with aforementioned interventions， once daily for 2 h each time， for 14 consecutive days. Mice in the control group underwent sham surgery， involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity， followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation， undergoing high-intensity treadmill exercise at a speed of 20 m/min， an inclination of 5°， for 30min per session， 5 times per week for 28 consecutive days， while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling， knee joint pathological changes were observed using HE and Safranin O-Fast Green staining， and quantified using Mankin and Osteoarthritis Research Society International （OARSI） scores. Serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were measured by ELISA. Protein and mRNA expression levels of pain-related markers， including calcitonin gene-related peptide （CGRP）， protein gene product 9.5 （PGP9.5）， and cellular proto-oncogene Fos （c-Fos）， and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 （TRPA1） and transient receptor potential melastatin 8 （TRPM8） in the dorsal root ganglion （DRG） tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group， the remaining groups showed decreased cold pain thresholds in the cold plate tese， increased cold pain thresholds in the acetone low-temperature test， elevated Mankin and OARSI scores， and increased serum TNF-α and IL-1β levels， upregulated protein and mRNA expression levels of CGRP， PGP9.5， c-Fos， TRPA1， and TRPM8 in the DRG， and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue （P＜0.05 or P＜0.01）， along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT， DMM， and intra-articular injection groups， the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators （P＜0.01）. Furthermore， changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group， DMM plus climate chamber and intra-articular injection plus climate chamber group （P＜0.01）， exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome， with the ACLT combined with the artificial climate chamber being the optimal modeling approach.

ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis （KOA） with cold-dampness obstruction syndrome， and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group， a treadmill plus climate chamber group， an anterior cruciate ligament transection （ACLT） plus climate chamber group， an ACLT group， a destabilization of the medial meniscus （DMM） plus climate chamber group， a DMM group， an intra-articular injection plus climate chamber group， and an intra-articular injection group， with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model， while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee， and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate （MIA） into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber （relative humidity 60%， temperature 4 ℃， wind speed 6 m/s） simultaneously with aforementioned interventions， once daily for 2 h each time， for 14 consecutive days. Mice in the control group underwent sham surgery， involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity， followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation， undergoing high-intensity treadmill exercise at a speed of 20 m/min， an inclination of 5°， for 30min per session， 5 times per week for 28 consecutive days， while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling， knee joint pathological changes were observed using HE and Safranin O-Fast Green staining， and quantified using Mankin and Osteoarthritis Research Society International （OARSI） scores. Serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were measured by ELISA. Protein and mRNA expression levels of pain-related markers， including calcitonin gene-related peptide （CGRP）， protein gene product 9.5 （PGP9.5）， and cellular proto-oncogene Fos （c-Fos）， and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 （TRPA1） and transient receptor potential melastatin 8 （TRPM8） in the dorsal root ganglion （DRG） tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group， the remaining groups showed decreased cold pain thresholds in the cold plate tese， increased cold pain thresholds in the acetone low-temperature test， elevated Mankin and OARSI scores， and increased serum TNF-α and IL-1β levels， upregulated protein and mRNA expression levels of CGRP， PGP9.5， c-Fos， TRPA1， and TRPM8 in the DRG， and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue （P＜0.05 or P＜0.01）， along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT， DMM， and intra-articular injection groups， the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators （P＜0.01）. Furthermore， changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group， DMM plus climate chamber and intra-articular injection plus climate chamber group （P＜0.01）， exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome， with the ACLT combined with the artificial climate chamber being the optimal modeling approach.

Objective:To explore and practice the construction of an innovative ecosystem that integrates innovation in the National Clinical Research Center for Orthopedics and Sports Rehabilitation, providing references and insights for driving high-quality development of medical care.Methods:Guided by a national policy framework and Industry-Academia-Research-Government-Enterprise Collaborative Innovation, the Center had established six innovation platforms and three systemic pillars. The study analyzed its integrated strategy, which encompassed ecosystem design, platform-enabled empowerment, comprehensive system support, end-to-end coverage, a folded innovation approach, and a standardization-driven mechanism.Results:The Center had built a highly integrated innovation ecosystem, creating a powerful driver for technological advancement and commercialization in orthopedics and sports rehabilitation, accelerating the industrialization of key technologies like surgical robots and 3D-printed implants.Conclusions:Guided by the principle of ″simplifying complex surgeries and standardizing common procedures″, the Center will leverage digital intelligence throughout clinical care, aiming to bridge gaps in healthcare quality so that patients can receive top-tier treatment for major diseases within their home provinces. This commitment to homogenized, high-quality care presents a ″China Model″ for global health and advance the national ″Healthy China″ initiative.

Objective To explore the potential cuproptosis-related genes(CRGs)in patients with multiple myeloma(MM)and develop a prognostic model for improving prognosis and revealing features of the MM immune microenvironment.Methods ① Transcriptome sequencing data and clinical information were retrieved from the GSE4581 dataset in the Gene Expression Omnibus(GEO)database and the Cancer Genome Atlas-Multiple Myeloma Research Foundation(TCGA-MMRF)database.The 859 patients from the TCGA-MMRF database were assigned into a training set,and the other 414 ones from the GSE4581 dataset into a validation set.LASSO-Cox and multivariate Cox regression analyses were used to construct prognostic models and calculate risk scores.Based on the median risk score,they were categorized into high-and low-risk cohorts.Time-dependent receiver operating characteristic(ROC)and calibration curves were plotted to assess the predictive performance and accuracy of the model.The differences between the high-and low-risk cohorts were explored using Kaplan-Meier survival curve analysis and immune microenvironment correlation analysis.② RT-qPCR and Western blotting were used to verify the expression of prognostic model genes in MM cell lines and normal bone marrow single-nucleated cells,and CCK-8 assay,flow cytometry,and Western blotting were applied to verify the biological function of UBE2D1 in MM cells.Results ① LASSO-Cox and multivariate Cox regression analyses revealed that the model consisted of 4 genes,CDKN2A[HR=1.60(95%CI:1.24～2.05),P=2.5e-4],PDE3B[HR=1.33(95%CI:1.09～1.62),P=4.2e-3],UBE2D1[HR=1.65(95%CI:1.20～2.26),P=2.1e-3]and COA6[HR=1.35(95%CI:1.07～1.71),P=0.01].In the training set,the time-dependent ROC curves predicted that the area under curve(AUC)value of 1-,3-,and 5-year survival rate was 0.63,0.71,and 0.78,respectively,and in the validation set,the AUC value was 0.656,0.657,and 0.797,respectively.Calibration curve analysis showed excellent agreement in predicting 1-,3-,and 5-year prognosis.In the training set,Kaplan-Meier curves showed that patients in the high-risk cohort had a significantly shorter overall survival(OS)than the low-risk cohort[HR=2.18(95%CI:1.58～3.02),P<0.001],and in the validation set,the high-risk cohort still had a shorter OS than the low-risk cohort[HR=2.45(95%CI:1.49～4.05),P<0.001].Immune correlation analysis revealed that the ratios of immune cells,such as plasma cells and CD4+T cells were significantly lower in the high-risk cohort(P<0.05),and the risk scores were positively correlated with the expression of immune checkpoint CTLA-4,tumor-targeted therapeutic sites TNFSF4 and ENTPD1,and microenvironmental chemokines CXCL16,CCL8,and CCL16(P<0.05).② Remarkable differences were observed in the expression of all 4 prognostic model genes between the MM cell lines and normal bone marrow single-nucleated cells(P<0.05),and knockdown of UBE2D1 notably inhibited the proliferation of MM cells(P<0.05).Conclusion Our prognostic models based on CDKN2A,PDE3B,UBE2D1,and COA6 genes can predict the prognosis of MM patients.The risk scores of the genes are significantly correlated with immune infiltration in the tumor microenvironment,which providing new molecular markers for individualized therapy.

PANoptosis is a newly defined type of programmed cell death (PCD), which is triggered by a variety of stimuli and covers three known forms of PCD: apoptosis, pyroptosis and necroptosis. In physiological state, cell death plays an important protective role against pathogen invasion, but its over-activation may aggravate inflammatory response and cause tissue damage. Studies have shown that the occurrence and progression of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases are closely related to PANoptosis. The purpose of this review is to deeply explore the molecular mechanism of PANoptosis and its regulatory factors in lung diseases, in order to discover potential therapeutic targets and provide new targets and innovative ideas for clinical treatment for lung diseases.
Humans ; Lung Diseases ; Apoptosis ; Pyroptosis ; Pulmonary Disease, Chronic Obstructive ; Necroptosis ; Acute Lung Injury

Corn silk, a Traditional Chinese Medicine, has the effect of calming liver, cholagogue, detumescence and diuresis. Corn silk is also widely used as tea and functional food. Natural flavonoids have multiple biological activities, which are also the main bioactive components of corn silk. In the past decade, many new advances have been made in the chemistry, analysis, pharmacology, pharmacokinetics, and safety evaluation of corn silk flavonoids. The chemical composition research of flavonoids has enriched the variety of flavonoids in corn silk. Pharmacological studies have confirmed and expanded the efficacy of corn silk flavonoids. And safety evaluation has provided a theoretical basis for the safe application of corn silk flavonoids. Through literature search, the extraction, separation, compositional analysis, content determination, pharmacological effect, pharmacokinetics, and safety research progress of corn silk flavonoids in the past ten years were reviewed in this paper.

Acupuncture and moxibustion have their unique advantages in treating tumors,but the theoretical framework of acupuncture and moxibustion intervention in tumors needs to be improved,and the academic system still needs to be sorted out.In this paper,we try to describe the commonalities between Chinese medical theories and modern medical technologies in order to consolidate the theoretical foundation of acupuncture intervention in tumor.Specifically:① Acupuncture regulates immune function and energy metabolism,which is a specific form of tonifying the spleen and stomach to support positive qi.② Tumors belong to the broad definition of"sores and ulcers"in traditional Chinese medicine,which is a special kind of chronic inflammation,and acupuncture intervenes in tumors by intervening in inflammatory reactions from ulcers.③ Tumor is a"dynamic pseudo-organ"with yin and yang attributes and"life attributes".Acupuncture and moxibustion can regulate various cells and factors in the tumor environment in a multi-targeted way,so as to make it tend to the state of yin and yang equilibrium.④ Acupuncture and moxibustion have unique advantages in the reduction of toxicity,enhancement of efficacy,tonicity,rejuvenation,treatment of complications,etc.,which complement the allopathic therapies of modern medicine,and can help to realize survival with tumors.

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

Depression is a mental disorder char-acterized by mood disturbances that pose a signifi-cant threat to human mental and physical health.In recent years,the farnesoid X receptor(FXR)has been found to be expressed in brain regions such as the hippocampus and is closely related to the onset of depression.It can also affect the down-stream target cAMP response element binding pro-tein(CREB)-brain-derived neurotrophic factor(BDNF)signaling pathway,holding promise as a new target for the treatment of depression.This ar-ticle analyzes how hippocampal FXR regulates the CREB-BDNF signaling pathway and summarizes the latest research progress related to the pathogene-sis of depression,with the aim of providing precise targeted ideas for the drug development and clini-cal treatment of depression.

Acupuncture and moxibustion have their unique advantages in treating tumors,but the theoretical framework of acupuncture and moxibustion intervention in tumors needs to be improved,and the academic system still needs to be sorted out.In this paper,we try to describe the commonalities between Chinese medical theories and modern medical technologies in order to consolidate the theoretical foundation of acupuncture intervention in tumor.Specifically:① Acupuncture regulates immune function and energy metabolism,which is a specific form of tonifying the spleen and stomach to support positive qi.② Tumors belong to the broad definition of"sores and ulcers"in traditional Chinese medicine,which is a special kind of chronic inflammation,and acupuncture intervenes in tumors by intervening in inflammatory reactions from ulcers.③ Tumor is a"dynamic pseudo-organ"with yin and yang attributes and"life attributes".Acupuncture and moxibustion can regulate various cells and factors in the tumor environment in a multi-targeted way,so as to make it tend to the state of yin and yang equilibrium.④ Acupuncture and moxibustion have unique advantages in the reduction of toxicity,enhancement of efficacy,tonicity,rejuvenation,treatment of complications,etc.,which complement the allopathic therapies of modern medicine,and can help to realize survival with tumors.