Heterotopic ossification is an important pathological link leading to disability in ankylosing spondylitis （AS）. Imbalance of bone immune microenvironment is the initiating factor for heterotopic ossification in AS， while abnormal osteogenic potential of bone marrow mesenchymal stem cells （BMSCs） is the core link. From the perspective of "bone sweat pore-kidney visceral manifestation" in traditional Chinese medicine， it is believed that dysfunction of "kidney visceral manifestation" is the basis for the induction of heterotopic ossification by bone immune microenvironment and BMSCs， and "bone sweat pore" is their important setting. Accordingly， it is proposed that the kidney and sweat pore should be nourished and regulated to reshape the bone immune microenvironment and BMSCs function， and that obstruction should be removed and the marrow should be unblocked to eliminate the pathological factors that lead to AS heterotopic ossification. This provides a new perspective and basis for the treatment of AS with traditional Chinese medicine.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective:To investigate the dynamic changes of diaphragm and limb skeletal muscle in patients with sepsis by bedside ultrasound and their correlation with the ratio of blood urea/creatinine ratio (UCR) in 7 days after intensive care unit (ICU) admission.Methods:A prospective observational study was conducted. A total of 55 patients with sepsis admitted to ICU of General Hospital of Ningxia Medical University from June 2022 to February 2023 were selected as the research objects. General information, laboratory indicators [urea, serum creatinine (SCr), and UCR] on days 1, 4, and 7 of ICU admission, and prognostic indicators were observed. Bedside ultrasound was used to assess the dynamic changes of diaphragm morphology [including diaphragmatic excursion (DE), end-inspiratory diaphragm thickness (DTei), and end-expiratory diaphragm thickness (DTee)] on days 1, 4, and 7 of ICU admission, as well as limb skeletal muscle (quadriceps femoris) morphology [including rectus femoris-muscle layer thickness (RF-MLT), vastus intermedius-muscle layer thickness (VI-MLT), and rectus femoris-cross sectional area (RF-CSA)]. Diaphragm thickening fraction (DTF) and RF-CSA atrophy rate were calculated, and the incidence of diaphragm and limb skeletal muscle dysfunction was recorded. The correlation between ultrasound morphological parameters of diaphragm and quadriceps and UCR at each time points in 7 days after ICU admission was analyzed by Pearson correlation.Results:A total of 55 patients with sepsis were included, of which 29 were in septic shock. As the duration of ICU admission increased, the incidence of diaphragm dysfunction in patients with sepsis increased first and then decreased (63.6%, 69.6%, and 58.6% on days 1, 4, and 7 of ICU admission, respectively), while the incidence of limb skeletal muscle dysfunction showed an increasing trend (54.3% and 62.1% on days 4 and 7 of ICU admission, respectively), with a probability of simultaneous occurrence on days 4 and 7 of ICU admission were 32.6% and 34.5%, respectively. The UCR on day 7 of ICU admission was significantly higher than that on day 1 [121.77 (95.46, 164.55) vs. 97.00 (70.26, 130.50)], and RF-CSA atrophy rate on day 7 was significantly higher than that on day 4 [%: -39.7 (-52.4, -22.1) vs. -26.5 (-40.2, -16.4)]. RF-CSA was significantly lower on day 7 compared to day 1 [cm 2: 1.3 (1.0, 2.5) vs. 2.1 (1.7, 2.9)], with all differences being statistically significant (all P < 0.05). Pearson correlation analysis showed that RF-CSA on day 7 of ICU admission was negatively associated with the UCR on the same day ( r = -0.407, P = 0.029). Conclusions:Diaphragmatic dysfunction in patients with sepsis occurred early and can be improved. Limb skeletal muscle dysfunction occurred relatively later and progresses progressively. The RF-CSA on day 7 of ICU admission may be a reliable measure of limb skeletal muscle dysfunction in patients with sepsis, can be an indicator of early identification and diagnosis of ICU-acquired weakness (ICU-AW). Continuous loss of muscle mass occurring in septic patients is mainly associated with persistent organismal catabolism, and undergoes significant changes around a week in ICU.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

Objective:To explore the application value of dynamic monitoring of gastric residual volume (GRV) in achieving different target energy in severe mechanical ventilation patients.Methods:A prospective randomized controlled study was conducted. Forty-two patients with mechanical ventilation admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from July to December 2022 were enrolled. According to the random number table method, patients were divided into GRV guided enteral nutrition by traditional gastric juice pumpback method (control group, 22 patients) and GRV guided enteral nutrition by bedside ultrasound (test group, 20 patients). General data were collected from both groups, and clinical indicators such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), neutrophil percentage (Neut%), procalcitonin (PCT), absolute lymphocytes (LYM), prealbumin (PA), and retinol-binding protein (RBP) were dynamically observed. Inflammation, infection, immunity, nutritional indicators, and the incidence of reflux/aspiration, ventilator-associated pneumonia (VAP) were compared between the two groups, and further compared the proportion of patients with respectively to reach the target energy 25%, 50%, and 70% on days 1, 3, and 5 of initiated enteral nutrition.Results:① There were no significant differences in gender, age, body mass index (BMI), duration of mechanical ventilation, and acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), severe nutritional risk score (NUTRIC) at admission between the two groups, indicating comparability. ② On day 1 of initiated enteral nutrition, there were no significant differences in infection, inflammation, immunity and nutrition indicators between the two groups. On day 3 of initiated enteral nutrition, the hs-CRP in the test group was lower than that control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 129.60±75.18 vs. 185.20±63.74, LYM: 1.00±0.84 vs. 0.60±0.41, PA (mg/L): 27.30±3.66 vs. 22.30±2.55, all P < 0.05]. On day 5 of initiated enteral nutrition, the hs-CRP, Neut%, PCT in the test group were lower than those control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 101.70±54.32 vs. 148.40±36.35, Neut%: (85.50±7.66)% vs. (92.90±6.01)%, PCT (μg/L): 0.7 (0.3, 2.7) vs. 3.6 (1.2, 7.5), LYM: 1.00±0.68 vs. 0.50±0.38, PA (mg/L): 27.10±4.57 vs. 20.80 ± 3.51, all P < 0.05]. There were no significantly differences in IL-6 and RBP between the two groups at different time points. ③ The proportion of 50% and 70% of achieved target energy in the test group on day 3, day 5 of initiated enteral nutrition were higher than those of the control group (70.0% vs. 36.4%, 70.0% vs. 36.4%, both P < 0.05). ④ The incidence of reflux/aspiration and VAP in the test group on day 5 of initiated enteral nutrition were significantly lower than those control group (incidence of reflux/aspiration: 5.0% vs. 28.6%, incidence of VAP: 10.0% vs. 36.4%, both P < 0.05). Conclusion:Dynamic monitoring of GRV by bedside ultrasound can accurately improve the proportion of 50% of achieved target energy on day 3 and 75% on day 5 in severe mechanical ventilation patients, improve the patient's inflammation, immune and nutritional status, and can prevent the occurrence of reflux/aspiration and VAP.

Objective To explore the mechanism of Prunella vulgaris and Scutellaria barbata herb pair against breast cancer based on network pharmacology and in vitro cell experiments.Methods The effective components and targets of Prunella vulgaris and Scutellaria barbata herb pair were screened.GeneCards and OMIM databases were used to find breast cancer targets,and then drug-active ingredient-key target network and protein-protein inter-action(PPI)were constructed.R language was used to perform GO function and KEGG pathway enrichment analy-sis and survival analysis.Then the screened active components and core targets were verified by molecular docking.Cell viability was detected by CCK-8 assay.EdU and flow cytometry were used to detect cell proliferation and apop-tosis.The protein expression levels of p-AKT1,AKT1,β-catenin and c-MYC were detected by Western blot.Results Through databases analysis,a total of 36 active components and 105 intersection targets were screened out,the core components were quercetin,luteolin,kaempferol,wogonin and baicalein.Through PPI and survival analysis,the key targets were AKT1,ESR1,CASP3 and MYC.GO analysis contained 4 303 enrichment results,KEGG analysis contained 232 pathways.Molecular docking showed that the core components had strong binding ability with the key targets.Cell experiments showed that the core active ingredient quercetin could inhibit the proliferation of breast cancer cells and promote their apoptosis(P＜0.05),and down-regulate the expression levels of p-AKT1,β-catenin and c-MYC proteins(P＜0.05).Conclusion The active components quercetin in Prunella vulgaris and Scutel-laria barbata herb pair may play a role through AKT1/β-catenin signaling pathway,which provides a scientific refer-ence for the study of its mechanism of action in the treatment of breast cancer.

Synthetic cannabinoids(SCs)are synthetic psychoactive substances that can pose a public health risk.The SCs are structurally variable and susceptible to structural modification.The rapid emergence of structurally unknown synthetic cannabinoids has led to new challenges in their identification.In recent years,machine learning has made great progress and has been widely applied to other fields,providing new strategies for the identification of unknown synthetic cannabinoids and the inference of possible sources.This paper describes the principles of commonly used machine learning methods and the application of machine learning techniques to mass spectrometry,Raman spectroscopy,metabolomics and quantitative conformational relationships of synthetic cannabinoids,aiming to provide new ideas for the identification of unknown synthetic cannabinoids.

Ankylosing spondylitis is a refractory autoimmune disease,and heterotopic ossification is one of the most important pathological features.The mechanism of heterotopic ossification in ankylosing spondylitis involves many aspects,including ossification-related genes,ossification-related factors,ossification-related cells,ossification signaling pathways,and mechanical stress.This article elaborates the pathogenesis of heterotopic ossification in ankylosing spondylitis from different aspects of multiple channels,pathways,targets,and factors,hoping to provide reference for expanding clinical and basic research and in-depth understanding of ankylosing spondylitis.

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast can-