Stasis-heat is a pathological factor associated with numerous exogenous and internal injuries, representing a pivotal mechanism in disease progression. Its primary cause is fire-heat toxicity. Based on the theory of qi and the holistic perspective of traditional Chinese medicine, this concept emphasizes that the biochemistry of all natural phenomena relies on the dynamic movement of qi ascending, descending, exiting, and entering. Within six qi, "fire" includes sovereign and ministerial fires. While physiological ministerial fire is the source power of life, pathological ministerial fire manifests as violent, intense energy that readily interacts with blood, leading to the formation of stasis-heat. Therefore, this article examines the formation and treatment of stasis-heat resulting from ministerial fire dysfunction. From the perspectives of ministerial fire gasification, the shape and quality of meridians, and the elevation of ministerial fire, it elucidates why the "pericardium-sanjiao-gallbladder" axis is regarded as pivotal. Furthermore, when the "pericardium-sanjiao-gallbladder" ministerial fire axis is unfavorable, and the stagnation of ministerial fire elevation and blockage is crucial to stasis-heat formation. Additionally, the depletion of essence and blood in the liver and kidneys, preventing the proper storage of ministerial fire, forms the pathological foundation. Drawing upon The Inner Canon of Yellow Emperor, this article explores therapeutic principles based on the rules of odor treatment: "when fires in the interior, the treatment of salty and cold, accompanied by bitter and pungent, acid to astringe, bitter to disperse." These principles are applied to achieve specific therapeutic goals: tempering the excess of ministerial fire to cool the nutritive level and transform stasis; adjusting the imbalance of elevation and depression to vent heat and unblock stasis; and restoring the misplaced fire by nourishing blood to expel stasis. Through these approaches, the article aims to reestablish the proper circulation of ministerial fire, dissipate blood stasis, and ultimately eliminate stasis-heat, thereby offering an integrated perspective on its pathogenesis and treatment.

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*

ObjectiveTo explore the elements， distribution and characteristics of traditional Chinese medicine （TCM） syndromes in depressive episodes of bipolar disorder （BD）. MethodsBasic information， along with the four examination information， the Hamilton Depression Scale and Young Mania Rating Scale scores， were collected from 293 outpatients with BD at Beijing Anding Hospital， Capital Medical University. The four examination information with an occurrence rate greater than 12% were retained. The R language “dist” function was used to calculate the distances between samples using the Euclidean distance method. The hierarchical clustering of the four examination information was performed using the “hclust” function and the squared Euclidean distance method. A team of five researchers was formed to determine the nature and location of the essential elements of TCM syndrome in BD based on the clustering results. The PC algorithm was used to construct a Bayesian network model of the essential elements. The working group combined the essential elements of TCM syndromes in the Bayesian network according to the reference model results， and then extracted common TCM syndromes. The score of each patient based on the essential elements was matched with the common TCM syndromes to determine the syndrome type of each patient. The working group then performs conformity and revision based on this， obtaining the final distribution of TCM syndromes for the patients. ResultsThere were 77 common TCM symptoms in BD with a frequency greater than 12%. The top 15 symptoms with higher frequencies were slippery pulse， mental fatigue and lack of strength， wiry pulse， excessive rumination， preference for solitude， vexation， agitation and irritability， dry mouth， palpitations， profuse dreaming， unwarranted worries， chest oppression， thin white coating， amnesia， frequent sighing， and poor appetite. TCM syndrome elements of BD can be grouped into 11 categories. The nature of disease-related essential elements included fire， qi deficiency， blood deficiency， qi counterflow， yin deficiency， dampness， heat， fire from constraint， and phlegm. The location of disease-related essential elements included heart， liver， spleen， stomach， kidney， bladder channel， and gallbladder. By constructing a Bayesian network model and considering the opinions from the experts， six common syndromes of BD were identified， among which the highest proportion was heart-stomach heat accumulation， accounting for 27.99% （82 cases）， followed by heart-spleen deficiency （55 cases， 18.77%）， non-interaction between the heart and the kidney （49 cases， 16.72%）， liver constraint and blood deficiency （42 cases， 14.33%）， heart qi deficiency （37 cases， 12.63%）， and damp-heat in the liver and gallbladder （28 cases， 9.56%）. ConclusionsThe nature of disease-related elements of BD are predominantly fire and heat， while the location of disease-related essential elements are primarily associated with the heart， liver， and spleen. The most common TCM syndromes are heart-stomach heat accumulation and heart-spleen deficiency.

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.

ObjectiveTo analyze the relationship between somatic symptoms， five-state personality and emotional symptoms of bipolar disorder （BD）， and to provide a reference for the clinical diagnosis and treatment of BD. MethodsThe basic information of the BD patients was collected， and the self-administered somatic symptom questionnaire was used to investigate the somatic symptoms with a frequency of ＞20%， which were scored as the somatic symptom scores； the 24-item Hamilton Depression Scale （HAMD） was used to evaluate the patients' depressive symptoms， the Young Mania Rating Scale （YMRS） was used to evaluate the patients' manic symptoms， the Hamilton Anxiety Scale （HAMA） was used to evaluate the patients' anxiety symptoms， and Five-State Personality Test was used to evaluate the patients' five-state personality （including taiyang personality， shaoyang personality， yin-yang balance personality， shaoyin personality， and taiyin personality）. Network analysis and linear regression were used to analyse the correlation between the somatic symptom scores and the five-state personality scores， HAMD scores， YMRS scores， and HAMA scores. ResultsThere were 269 patients with BD included， and 19 somatic symptoms with a frequency of ＞20%， the top three being lack of strength （152 cases， 56.51%）， dry mouth （137 cases， 50.93%）， and preference for cold drinks （112 cases， 41.64%）， and the somatic symptom scores were ［7.0 （0，10.0）］ points； the YMRS scores were ［3.0 （0， 7.5）］ points； the HAMD scores were ［11.0 （5.0， 18.0）］ points； and HAMA score was ［6.0 （2.0， 10.0）］ points. Among the five-state personalities， taiyang personality ［10.0 （7.0， 13.0）］ score； shaoyang personality ［10.0 （7.5， 13.0）］ score； yin-yang balance personality ［5.0 （3.0， 7.0）］ score； shaoyin personality ［13.0 （10.0， 16.0）］ score； and taiyin personality ［14.0 （9.0， 18.0）］ score. Complex network analysis showed that BD somatic symptoms were positively correlated with taiyin personality score （r = 0.23）， HAMD score （r = 0.21）， and YMRS score （r = 0.13）； taiyin personality score was positively correlated with HAMD score （r = 0.17） and negatively correlated with YMRS score （r = -0.03）. Linear regression analyses showed that somatic symptom scores were positively correlated with HAMD score （β = 0.138， P = 0.003）， YMRS score （β = 0.128， P = 0.006）， and taiyin personality scores （β = 0.182， P＜0.001）. ConclusionDepression， mania， and taiyin personality are independent risk factors for somatic symptoms in patients with BD， and taiyin personality is strongly associated with somatic symptoms in patients with BD.

OBJECTIVE To explore the effects of the water extract of Morinda officinalis on the expressions of sex hormones and receptors in bisphenol A （BPA）-contaminated mice. METHODS Totally 60 male Kunming mice were randomly divided into control group， model group， and low-dose， medium-dose and high-dose groups of M. officinalis water extract （20， 40， 60 mg/kg）， with 12 mice in each group. The model group and M. officinalis water extract groups were given BPA intragastrically [50 mg/（kg·d）， once a day， for 4 consecutive weeks] to establish the BPA-contamination model of mice. After modeling， each drug group was gavaged with the corresponding drug solution， once a day， for 4 consecutive weeks. After the last medication， the body weight and testicular weight of the mice in each group were weighed， the histopathological changes in the testis were observed， and the serum sex hormones [luteinizing hormone （LH）， follicle-stimulating hormone （FSH）] contents and the mRNA and protein expressions of LH receptor （LHR） and FSH receptor （FSHR） in the testicular tissues were detected. RESULTS Compared with the control group， the testicular tissues of mice in the model group had structural degeneration， loose connections between spermatogenic cells and Sertoli cells， obvious lacunae and reduced number of spermatogenic cells； the mRNA and protein expressions of LHR and FSHR in testicular tissues were significantly down-regulated （P＜0.01）， but there were no significant changes in their body weights， testicular weights， and serum contents of LH and FSH （P＞0.05）. Compared with the model group， the histopathological changes of testicular tissues of mice in each dose group of M. officinalis water extract were improved to different degrees， and the mRNA and protein expressions of LHR and FSHR in testicular tissues were up-regulated to different degrees （P＜0.05 or P＜ 0.01）， and some indicator levels were similar to those of the control group （P＞0.05）. However， there were no significant changes in their body weights， testicular weights， and serum contents of LH and FSH （P＞0.05）. CONCLUSIONS The water extract of M. officinalis has a certain improvement effect on testicular injury in BPA-contaminated mice， which might be related to its increase in the mRNA and protein expressions of LHR and FSHR.

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 The aim of this study is to combine Raman spectroscopy and machine learning techniques to distinguish subgin-gival plaques among three groups of subjects,including patients with chronic periodontitis(CP)and type 2 diabetes mellitus(T2DM),patients with CP alone,and healthy controls.Methods The Raman spectra of the subgingival plaques from 20 patients with CP and T2DM(group A),23 patients with CP alone(group B),and 23 healthy controls(group C)were obtained using a portable Raman spec-trometer.Eight common machine learning algorithms were applied to build models to distinguish the Raman spectra of the three types of subgingival plaques.Results The model identified as optimal for distinguishing the three types of subgingival plaques was linear discri-minant analysis(LDA).The optimal model to distinguish groups A and B is LDA,groups A and C is extra trees(ET),and groups B and C group is LDA.Conclusion The proposed classification model based on Raman spectroscopy and machine learning algorithms can dis-tinguish subgingival plaques among patients with CP and T2DM,with CP alone,and healthy controls.This technique can be used in future clinical practice as a screening or diagnostic tool.

Objective:To evaluate the risk factors for diaphragmatic dysfunction of patients with sepsis and septic shock, and the application value of bedside ultrasound.Methods:Patients with sepsis and septic shock in the Intensive Care Unit (ICU), General Hospital of Ningxia Medical University from January 2020 to May 2021 were prospectively recruited as the research subjects, general postoperative patients and healthy volunteers were admitted as postoperative control and normal control groups. General clinical data were collected, patients with sepsis and septic shock were dynamically observed high sensitive c-reactive protein (hs-CRP), interleukin-6 (IL-6), serum albumin, transferrin, prealbumin levels, blood lactate, Pcv-aCO 2, ScvO 2, etc.; and indirect calorimetry was used to measure the resting energy level of the patient to calculate the missing energy value. Bedside ultrasound was used to dynamically evaluate the changes of diaphragm excursion (DE),inspiratory diaphragm thickness, and expiratory diaphragm thickness, to calculate relevant parameters. DE<10 mm or diaphragmatic thickness fraction (DTF) < 20% was diagnosed as diaphragmatic dysfunction. Results:(1) On day 1 in the ICU, the DE of the septic shock group, sepsis group and postoperative control group were significantly lower than that in the normal control group [10.3 (9.0, 13.6) mm, 12.3 (9.1, 15.0) mm, 12.9 (10.5, 15.7) mm vs. 22.0 (16.0, 24.6) mm, all P<0.05], and the incidence of DTF<20% was significantly higher than in the normal control group (32.7%, 41.9%, 33.3% vs. 0 %, all P<0.05), and the incidence of DE<10 mm in the septic shock group and sepsis group was significantly higher than that of postoperative control group and normal control group (36.7%, 35.5% vs. 10.0%, 0%, respectively, all P<0.05). On day 7, the DE in the septic shock group was significantly lower than that in the sepsis group [10.5 (6.8, 13.5) mm vs. 14.4 (10.6, 18.6) mm, P<0.05].(2) Correlation analysis of each index: The DE of patients with sepsis and septic shock on day 1, 3, and 7 was negatively correlated with the hs-CRP ( r=-0.253, -0.436, -0.455, all P<0.05); On day 3, DE was also negatively correlated with IL-6 ( r=-0.338, P=0.009); and DTF was negatively correlated with hs-CRP ( r=-0.375, P=0.004). On day 1, there was a positive correlation between DTF and serum transferrin levels in patients with sepsis and septic shock ( r=0.221, P=0.049). On day 3 and 7, the DE was positively correlated with serum prealbumin levels ( r=0.318, 0.408, both P<0.05). Conclusions:Patients with sepsis and septic shock have developed diaphragmatic dysfunction on day 1 in the ICU, which is mainly manifested as decreased in diaphragm mobility and diaphragmatic thickness fraction, and is related to inflammation and high protein catabolism.

The outcome of hepatitis B virus (HBV) infection is determined by the complex interaction between the host's immune system and the virus and the proteins it produces, leading to the occurrence of acute and chronic liver diseases. In acute hepatitis B (AHB), the virus is cleared by the host through innate immunity and strong adaptive immunity. In chronic hepatitis B (CHB), both the innate and adaptive immunity of the host are continuously inhibited by HBV and the proteins it produces, which are not conducive to virus clearance. This article reviews the recent studies on innate immunity and adaptive immunity of acute and chronic viral hepatitis B, in order to provide ideas for further research and provide evidence for new clinical treatment method.