Research on inflammatory response,liver injury,and immune regulation has demonstrated that the intricate interactions among immune cells constitute a critical regulatory network.Alcohol consumption alters the liver microenvironment,triggering inflammation and immune responses.Elucidating the inhibitory,cooperative,and synergistic effects among lymphocytes and myeloid cells may reveal the core mechanisms of alcohol-associated liver disease(ALD)pathogenesis and identify promising therapeutic targets.This review seeks to elucidate the intricate and multifaceted interactions among immune cells,encompassing both direct cellular interactions and the secretion of various effector molecules.It is essential to underscore that these interactions have broader and more complex roles in ALD than the activities of individual immune cell types.These interactions play a crucial role in mutually regulating one another,thereby preserving the homeostasis of the inflammatory and immune response in the liver environment.Targeting these immune cell interactions is anticipated to offer a novel approach to the prevention and treatment of ALD.

Objective To explore the spatial distribution of microstructural parameters and mechanical properties for trabecular bone in the femoral head with osteonecrosis. Methods Microstructural parameters and mechanical properties of trabecular bone in different regions were analyzed by combined use of imaging measurements and numerical simulation method, and the spatial distribution of biomechanical properties for trabecular bone along coronal, sagittal and vertical directions was investigated. Results Microstructural characteristics and mechanical properties of trabecular bone were Y-shaped distributed along coronal and sagittal directions, and mechanical properties of trabecular bone in Y-shaped region were higher than those in the other regions. Such distribution characteristics was consistent with the location of principle compressive group in the femoral head. Conclusions Necrotic lesions in Y-shaped region had a greater influence on stress distribution of the femoral head and might cause the deterioration of osteonecrosis. The spacial correlation between necrotic lesions and Y-shaped region should be fully considered during clinical diagnosis.

Objective:To explore the relationship between constitutional types of Chinese medicine and Alzheimer's disease (AD) and to construct an early warning model for AD risk.Methods:In the established multimodal interventions to delay dementia and disability in rural China (MIND-China) study, 4 033 elderly subjects aged ≥60 years old were included. The data including demographic, underlying disease and neuropsychological data were collected.The Chinese medicine service record form for the elderly was used to assess constitutional types of Chinese medicine and to apply the NIA-AA diagnostic criteria published by the National Institute on Aging and the Alzheimer's Association in 2011 for the diagnosis of clinically likely AD. Logistic regression analysis and AD risk prediction models were constructed using R statistical software, and the final prediction results were presented using columnar plots.Results:The MIND-China cohort was dominated by the abnormal constitution (69.28%), of which Phlegm-wetness type was the most common (58.05%), followed by Yang-deficiency type (23.85%). The most constitutional type of Chinese medicine among AD patients was Phlegm-wetness type (54.35%), followed by Qi-depression type (38.04%). Multi-factorial logistic regression analysis suggested that increasing age ( β=0.101, P<0.001, OR=1.107, 95% CI=1.069-1.146) and Qi-depression type ( β=0.622, P=0.016, OR=1.862, 95% CI=1.116-3.076) were able to increase the risk of developing AD, while education ( β=-1.047, P<0.001, OR=0.351, 95% CI=0.205-0.584) was able to reduce the risk of developing AD. By using the risk score model to calculate the total risk score for each subject and plotting the receiver operating characteristic curve (ROC), the area under the ROC was 0.769 and the calibration curve showed excellent consistency between prediction and reality. Conclusion:Older adults with Qi-depression type are significantly associated with an increased likelihood of AD.

ObjectiveTo observe the intervention effect of Ruyi Zhenbao pills （RYZBP） on central pain after thalamic stroke in mice and explore the underlying mechanism. MethodThe central post-stroke pain syndrome （CPSP） model was induced by stereotactic injection of type Ⅳ collagenase into the hypothalamus in mice. The mice were divided into a sham group， a model group， low-， medium-， and high-dose RYZBP groups （0.65， 1.3， 2.6 g·kg^-1）， and a pregabalin group （0.075 g·kg^-1）. Seven days after modeling， the mice in the groups with drug intervention were administered with corresponding drugs by gavage according to the body mass， once per day for 25 days， while those in the sham group and the model group received an equal volume of normal saline. During this period， mechanical pain and cold pain were detected at different time points， and the apoptotic state of brain tissue cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. The 36 classical broad-spectrum inflammatory factors were quantitatively analyzed by liquid-phase chip technology， and differential molecules were screened out and verified by Western blot and enzyme-linked immunosorbent assay （ELISA）. ResultCompared with sham operation group, mechanical pain threshold and cold sensitive pain threshold in model group were significantly changed （P<0.01）. TUNEL results showed that apoptosis of brain cells was obvious. Western blot and ELISA results showed that the expressions of interleukin-1α (IL-1α) and chemokine ligand 5 (CCL5) increased in hypothalamus tissue and serum， while the expressions of Ang-2, granulocyte-colony-stimulating factor (G-CSF) and IL-4 decreased significantly （P<0.01）. Compared with model group， RYZBW dose groups significantly increased mechanical pain threshold， decreased cold sensitivity pain threshold， decreased hypothalamus cell apoptosis ratio （P<0.01）， decreased the expression of IL-1α and CCL5 in hypothalamus tissue and serum， while the expression of ANG-2， G-CSF and IL-4 were significantly increased （P<0.05）. ConclusionRYZBP can relieve hyperalgesia in CPSP mice， and its mechanism is related to the regulation of the expression of pro-/anti-inflammatory factors IL-1α， CCL5， IL-4， G-CSF， and Ang-2.

Objective To measure mechanical properties of calcified tissues from human aortic valve by nanoindentation test. Methods Leaflets from 5 patients with aortic stenosis were collected. Elastic modulus and hardness of the calcified leaflets were obtained by nanoindentationtest. Results The elastic modulus and hardness of the calcified leaflets were (15.69±3.89) GPa and (0.59±0.15) GPa, respectively. Conclusions The elastic modulus and hardness of the calcified valve tissues can be obtained by nanoindentationtest, which provides experimental data for biomechanical research of the valve.

Objective:To investigate the relationship of interleukin (IL)-37, osteoprotegerin with coronary artery disease and its stenosisdegree.Methods:The prospective research method was used. From April 2018 to June 2019, two hundred and eleven suspected or diagnosed coronary artery disease patients who had chest pain or discomfort in Dalian Friendship Hospital were selected. The patients underwent selective percutaneous coronary angiography and completed coronary stenosis score (Gensini score). According to the degree of coronary stenosis, 211 patients were divided into the control group(coronary stenosis<50%, 45 cases), single-vessel stenosis group (single-vessel stenosis ≥ 50%, 52 cases), double-vesselstenosis group (double-vesselstenosis ≥ 50%, 58 cases), and triple-vessel stenosis group (triple-vessel stenosis ≥ 50%, 56 cases). The levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a, uric acid, creatinine were measured by the automatic biochemical analyzer. The serum levels of IL-37 and osteoprotegerin were detected by enzyme-linked immunosorbent assay.Results:There were no statistical differences in FBG, uric acid, creatinine, TC, TG, LDL-C, HDL-C, ApoA1 and ApoB among 4 groups ( P>0.05). In the control group, single-vessel stenosis group, double-vessel stenosis group and triple-vessel stenosis group, lipoprotein a was (0.266 ± 0.060), (0.283 ± 0.070), (0.289 ± 0.066) and (0.307 ± 0.084) mg/L respectively; coronary stenosis score was (8.27 ± 7.08), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) scores respectively; IL-37 was (342.27 ± 122.36), (437.45 ± 98.47), (493.72 ± 125.19) and (522.61 ± 149.34) ng/L respectively; osteoprotegerin was (378.29 ± 111.95), (458.39 ± 115.37), (502.50 ± 116.88) and (533.39 ± 139.83) ng/L respectively; and there were statistical differences among 4 groups ( P<0.05 or <0.01). IL-37, osteoprotegerin and lipoproteina were positively correlated with coronary stenosis score ( r = 0.43, 0.42 and 0.23, P<0.05), the osteoprotegerin was positively correlated with IL-37( r = 0.73, P<0.05). The multivariate linear regression analysis result showed that the IL-37 and osteoprotegerin were independent protective factors of coronary stenosis degree( β = 0.07 and 0.07, t = 2.72 and 2.57, P<0.01 or <0.05),and lipoproteina was independent risk factor of coronary stenosis degree ( β = 0.97, t = 2.89, P<0.01). Conclusions:IL-37 and osteoprotegerin are positively correlated with the degree of coronary stenosis. They are anti-inflammatory and protective factors of coronary heart disease.

OBJECTIVETo detect mutations of the XPC (XPC complex subunit, DNA damage recognition and repair factor) gene in a family affected with xeroderma pigmentosum group C (XP-C).

METHODSThe patient was subjected to next-generation sequencing and Sanger sequencing. Suspected mutations were validated by Sanger sequencing. Effect of splicing mutation was confirmed by reverse transcription-PCR (RT-PCR).

RESULTSCompound heterozygous mutations of c.2098G to T and c.2034-7_2040del were found in the XPC gene in the proband. Among these, c.2098G to T (p.G700X) is a nonsense mutation resulting in a truncated XPC protein. C.2034-7_2040del involves the -1 position, which may alter the splice donor site of the intron 11 of XPC and result in a truncated XPC protein with loss of amino acids from 940 to 679 positions. The two mutations were not detected among 100 unrelated healthy controls.

CONCLUSIONMutations of c.2098 G to T and c.2034-7_2040del of the XPC gene may lead to abnormal XPC expression and reduction or elimination of normal XPC functions, which may underlie the disease in this family.

Objective To study the effects of binary cardiac rehabilitation (CR) composed of hospital-based and home-based CR in patients after acute myocardial infarction (AMI) evaluated by six-minute walking distance (6MWD). Methods A total of 38 post-MI patients were divided into two groups, namely conventional CR group (n=20) and binary CR group (n=18). In the first seven days, CR training was carried out in all 38 patients in our hospital, and then 20 patients were kept at CR training in the hospital (hospital-based CR group), whereas the remaining 18 patients (binary CR group) got tele-monitored walking training at home for eight weeks (binary model). Before discharge from hospital based CR or after 8 weeks CR at home, all patients received Cardiopulmonary Exercise Testing and Six-minute Walk Test, and the data of patients' body mass index (BMI),thyroid function, serum lipid metabolism and echocardiography were collected before and after CR. Results After CR, BMI and low density lipoprotein (LDL) decrease in both groups compared with those before CR[hospital-based group: BMI, (25.99±3.36)kg/m2 vs. (23.04±3.72) kg/m2,P＜0.05; LDL, (3.40±1.38) mg/dl vs. (2.04±0.73)mg/ dl,P＜0.01; binary group: BMI, (24.84±2.70) kg/m2 vs. (22.88±2.56) kg/m2,P＜0.05; LDL, (3.40±1.01) mg/dl vs. (92.11±0.37) mg/dl,P＜0.01]. After 8 weeks CR at home or hospital based CR until discharge, the anaerobic threshold (AT), maximum rate of oxygen consumption (VO2max),metabolic equivalent (MET) and 6MWD improved significantly in both groups compared with those at 7 days after CR in hospital [Hospital-based group: AT, (12.37±1.53) mL/(kg. min) vs. (14.77±1.57) mL/(kg. min); VO2max (17.87± 1.66 mL/(kg. min) vs. (20.73±2.14) mL/(kg. min); MET (5.02±0.36) vs. (6.09±0.53); 6MWD (500±53.36) m vs. (582.5±57.6) m,P＜0.01; Binary group: AT, (12.56±1.11) mL/(kg·min) vs. (14.30±1.23) mL/(kg. min); V02max, (17.28±1.38) mL/(kg. min) vs. (20.02±1.37) mL/(kg. min); MET, (5.07±0.47)vs (5.94±0.46); 6MWD,(511.4±50.96) m vs. (590.3±56.1)m,P＜0.01]. There was no significant difference in CR effects observed between two groups (P＞0.05). Conclusions In post-MI patients,a binary model of CR training improved physical capacity and was a similarly effective form of CR as a entirely hospital-based approach. A home-based tele-monitored program facilitated patients' adherence to CR. The 6 minute walk experiment is economical and good evaluation on the CR effect of binary cardiac rehabilitation.

Objective To investigate the relation between 25-hydroxyvitamin D3[25(OH)D3] and coronary artery disease. Methods Three hundred and ten patients with selective coronary angiogram (CAG) were enrolled in this study and they were divided into two groups: non-coronary artery stenosis group with 76 patients and coronary artery stenosis group with 234 patients. The degree of coronary artery stenosis was evaluated by the international general Gensini integration system. The levels of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C) were detected by automatic biochemistry analyzer. The level of 25(OH)D3 was detected by tandem mass spectrometry. The relationship of Gensini integration scores and risk factors were analyzed. Logistic regression analysis was used in multicity factors analysis. Results The levels of age, Gensini integration scores, 25(OH)D3, FPG and LDL-C in non-coronary artery stenosis group and coronary artery stenosis group had significant differences (P<0.05). The number of coronary stenosis and Gensini integration scores in 25(OH) D3 deficiency group were significantly higher than those in non-25 (OH)D3 deficiency group (P<0.01). Logistic regression analysis showed that age, FPG and 25(OH)D3 levels were risk factors for coronary artery stenosis (P<0.01 or<0.05), and the level of 25(OH)D3 had negative correlation with coronary artery stenosis (B =- 0.100), and it was a protection factor (OR =0.904, 95%CI:0.911-0.983, P=0.000). Conclusions 25(OH)D3 deficiency is one of the risk factor of coronary artery disease.

Objective To investigate and optimize the condition of purification and crystallization of oncogenic protein MDM2.Methods MDM2 was expressed in E.coli expression system, and purified by Ni-NTA chelating affinity chromatography and molecular sieve chromatography.The secondary structure of purified protein was analyzed by circular dichroism spectroscopy (CD).Then the crystallization condition of MDM2 was screened and optimized by sitting-drop vapor-diffusion method.Results High purity of MDM2 was obtained by Ni-NTA chelating affinity chromatography and molecular sieve chromatography purification.CD analysis indicated the secondary structure of MDM2 was ordered.Protein-crystallisation experiments illustrated that MDM2 was prone to crystallization under lower pH.Conclusion The optimum pH of MDM2 protein crystallization is 5.5, the optimum protein concentration is 10 mg/mL.