Objective To observe the effects of Angelicae Sinensis Radix-Paeoniae Radix alba combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on liver inflammation and hepatocytes regeneration in non-alcoholic steatohepatitis(NASH)associated cirrhosis;To discuss its possible mechanism.Methods West diet combined with carbon tetrachloride was used to prepare the NASH related cirrhosis model.The mice were randomly divided into control group,model group,Angelicae Sinensis Radix-Paeoniae Radix alba group,BM-MSCs group,and Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,with 12 mice in each group.After successful modeling,corresponding interventions were given according to grouping for 4 consecutive weeks.HE staining was used to observe the morphology of liver tissue;the contents of serum ALT,AST,TBil,TG,ALB,AFP,as well as the contents of IL-1β,TNF-α and HGF in liver tissue were detected;RT-qPCR was used to detect TLR9,MyD88,TRAF6 and NF-κBp65 mRNA expression in liver cells;primary liver cells were separated,CpG ODN 2216 stimulation was induced in vitro,cells supernatant was extracted,and IL-1β and TNF-α content were detected.Results Compared with the control group,inflammatory cell infiltrated in liver tissue of model group mice,accompanied by hepatocyte necrosis and collagen deposition,forming pseudo lobules;the contents of serum ALT,AST,TBil and TG increased,the content of ALB decreased,the content of HGF in liver tissue decreased,the contents of IL-1β and TNF-α increased,with statistical significance(P<0.05);the mRNA expressions of TLR9,MyD88,TRAF6 and NF-κBp65 in liver cells increased(P<0.05),and the contents of IL-1β and TNF-α in cells supernatant increased after CpG ODN 2216 induction(P<0.05).Compared with the model group,the inflammatory infiltration in liver tissue and necrosis of liver cells were reduced and the degree of liver fibrosis was alleviated in the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,the liver tissue damage in Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group were slightly improved;except for the TG content in BM-MSCs group,all detection indicators showed significant improvement in each intervention group(P<0.05).Compared with the Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group,the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group showed statistical significance in related detection indicators(P<0.05),and demonstrated a synergistic effect.Conclusion Angelicae Sinensis Radix-Paeoniae Radix alba combined with BM-MSCs transplantation could effectively improve the liver function and promote liver cell regeneration.The mechanism is associated with the down-regulation of TLR9/NF-κB signaling pathway expressions and function,the inhibition of inflammatory cytokines secretions,and the improvement of liver inflammatory microenviroment.

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.
COVID-19/prevention & control* ; China/epidemiology* ; Humans ; Machine Learning ; Pandemics/prevention & control* ; Policy ; Reproducibility of Results ; SARS-CoV-2

Objective:To explore the effect of placing drainage or not on rapid rehabilitation after total knee arthroplasty (TKA). Methods:From January, 2018 to September, 2020, 80 patients with knee osteoarthritis who underwent primary TKA in our hospital were analyzed retrospectively, and they were divided into groups A and B, with 40 cases in each group. Drainage was placed routinely in group A and not in group B. The postoperative serum inflammatory factors, postoperative pain score, postoperative complication rate, postoperative time out of bed, hospital stay, knee function score, range of motion of knee and World Health Organization Quality Of Life-abbreviated version score (WHOQOL-BREF) were compared between two groups. Results:There was no significant difference in the levels of C-reactive protein between two groups on the 1st to 3rd day after operation (t < 0.410, P > 0.05). There was no significant difference in Visual Analogue Score between two groups from 12 h to 48 h after operation (t < 0.300, P > 0.05). The incidences of postoperative complications were 5.0% in group A and 2.5% in group B, with no significant difference between two groups (χ² = 0.346, P > 0.05). The time of getting out of bed and hospital stay was significantly shorter in group B than in group A (t > 4.863, P < 0.001). The scores of knee joint function, range of motion of knee and WHOQOL-BREF significantly increased after operation in both groups (t > 6.099, P < 0.001), however, there was no significant difference between two groups (P > 0.05). Conclusion:Placement or non-placement of drainage after primary TKA does not affect postoperative complications, knee joint function and quality of life of patients with knee osteoarthritis, however, non-placement of drainage can promote postoperative recovery and discharge.

Objective:To observe the activation of microglia and the expression of inflammatory factors in hippocampus of mice with depression-like behavior after mother-infant separation （MS） combined with lipopolysaccharide （LPS） stress， and to explore the possible anti-depression mechanisms of Wenyang （WY）， Jieyu （JY）， and Wenyang Jieyu （WYJY） prescriptions from the perspective of warming Yang and relieving depression. Method:Seventy offspring mice were randomly divided into a normal group （n=10）， a LPS stress group （n=10）， and a modeling group （n=50）. After undergoing 8 h·d^-1 mother-infant separation during postnatal day 5 （PD₅）–PD₁₄， mice in the modeling group were further divided into the MS + LPS group， WY group， JY group， WYJY group， and fluoxetine （FLU） group， with 10 in each group. The birth date of the offspring mice was recorded as PD₀. The mice in the normal， LPS， and MS + LPS groups were fed a normal diet during PD₂₁–PD₉₀， while those in the other groups were treated with the mixtures of corresponding drugs and feed， followed by seven-day intraperitoneal injection of LPS since PD₉₁ for inducing depression. The depression-like behavior of mice in each group was detected in the open-field， O-maze， and social interaction tests. The protein expression of microglia-specific ionized calcium-binding adaptor molecule 1 （Iba-1） in the hippocampus was assayed by immunohistochemistry， and the mRNA expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， Iba-1， and glucocorticoid receptor （GR） by real-time fluorescence quantitative PCR （Real-time PCR）. Result:Compared with the normal group， the LPS group exhibited significantly reduced residence time at the central area within 5 min （P<0.01） and shortened total exercise distance （P<0.01）. In the MS + LPS group， the open-arm activity time and the total activity distance decreased significantly （P<0.01， P<0.05）， whereas the training， discrimination and exploration time increased significantly （P<0.01）. The expression of Iba-1 in hippocampal CA1 region of mice in the LPS and MS + LPS groups was remarkably elevated （P<0.01）. Compared with the LPS group， the MS + LPS group displayed significantly prolonged distance of 5-min exercise （P<0.05）， increased training， discrimination and exploration time （P<0.05， P<0.01）， and up-regulated Iba-1 expression in hippocampal CA1 area （P<0.01）. As revealed by comparison with the MS + LPS group， both the total 5-min exercise distance （P<0.01） and the training and discrimination time （P<0.01， P<0.05） of mice in each administration group was significantly shortened. The discrimination and exploration time of mice in the JY， WYJY， and FLU groups was significantly reduced （P<0.01）， and the expression of Iba-1 in hippocampal CA1 region of mice in each administration group was significantly down-regulated （P<0.01）. Conclusion:The warming Yang and relieving depression method helps to inhibit the occurrence and development of depression due to its efficacy in activating microglia in hippocampus of depression mice and lowering the expression of IL-1β， IL-6， and TNF-α.

Objective:To observe the activation of microglia in hippocampus of depressed and anxious mice induced by maternal separation with acute restraint stress and the expression of interleukin-1β（IL-1β），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α）， investigating the mechanism of Wenyang Jieyu prescription in treating anxiety and depression. Method:Eighty four male C57BL offspring were randomly divided into control group， acute restraint stress group and model group on postnatal day 0（PD0）. Maternal separation combined with acute restraint stress was used to prepare anxious and depressed model mice， dividing the model mice into model group， Wenyang， Jieyu， Wenyang Jieyu and fluoxetine group according to random number table method. During the period of PD21-PD90， the control， acute restraint stress and model mice were fed with normal diet， with the other groups fed with corresponding medicine mixed diet. The Wenyang， Jieyu and Wenyang Jieyu groups were given 5.85， 12.03 and 16.71 g·kg^-1·d^-1 respectively. The fluoxetine group was given 2.60 mg·kg^-1·d^-1. Open field， zero maze test and social interaction tests were used to evaluate the anxiety and depression of model mice. The expression of Iba-1 in hippocampal microglia was detected by immunohistochemistry（IHC）. The mRNA expression of IL-1β， IL-6， TNF-α， Iba-1 and glucocorticoid receptor（GR）were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the control group， total movement distance and time spent in central zone in 5 min of the model mice significantly decreased（P<0.01）， time spent in opened arm and total movement distance decreased significantly（P<0.05，P<0.01）， investigation time during testing and training increased significantly（P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly increased（P<0.01）， the expression levels of GR mRNA significantly decreased（P<0.01）. The result of IHC staining showed that microglia were over activated. Compared with the model group， total movement distance and time spent in central zone in 5 min of mice in the Wenyang Jieyu and fluoxetine group significantly increased（P<0.05，P<0.01）.Time spent in opened arm significantly increased（P<0.01）. Investigation time during testing and training significantly decreased（P<0.05，P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly decreased（P<0.05，P<0.01）. The expression of GR mRNA increased significantly（P<0.05，P<0.01）. IHC staining showed the microglia recovered. Time spent in opened arm of mice in the Wenyang group and Jieyu group significantly increased （P<0.01）， time spent investigating during testing decreased significantly （P<0.05）， the expression levels of Iba-1 protein and mRNA，IL-6 mRNA significantly decreased （P<0.05，P<0.01）. The expression of GR mRNA of mice in the Wenyang group significantly increased （P<0.05）， the expression of TNF-α mRNA significantly decreased （P<0.05）. Total movement distance of mice in the Jieyu group increased significantly （P<0.01）， time spent investigating during training decreased significantly （P<0.05），the expression level of IL-1β mRNA significantly decreased （P<0.05）. IHC staining showed that microglia recovered partly in both groups. Conclusion:The comprehensive curative effect and pharmacological action of Wenyang Jieyu prescription were better than Wenyang prescription and Jieyu prescription. Wenyang Jieyu prescription can treat anxiety and depression in maternal separation and acute restraint stress mice， its possible mechanism may be related to the decreased activation of microglia， down-regulation of IL-1β，IL-6，TNF-α expression and up-regulation of GR expression.

Objective:To investigate the clinical effect of Chaihu Shugansan combined with abdominal acupuncture on depression caused by chronic pain，and to explore its mechanism. Method:A total of 97 patients with depression caused by chronic pain were randomly divided into control group （49 cases） and observation group （48 cases）. Patients in both groups received routine western medicine treatment，including necessary psychological intervention and taking paroxetine. Control groupobservation groupcontrol group Patients in control group were treated with Xiaoyaowan，and patients in observation group were treated with Chaihu Shugansan combined with abdominal acupuncture. Both groups were treated for 6 weeks. The levels of serum neurotransmitters，cytokines and Hamilton depression rating scale（HAMD） before and after treatment were compared between two groups. Result:There was no significant difference in HAMD scores of the two groups before treatment and the HAMD scores of two groups after treatment were significantly lower than those before treatment （P<0.05），and the HAMD scores in observation group were significantly lower than those in the control group （P<0.05）. There was no significant difference in the levels of serum 5-hydroxytryptamine （5-HT），norepinephrine （NE），and brain-derived neurotrophic factor （BDNF） between two groups before treatment. After treatment，the levels of serum 5-HT，NE，and BDNF in two groups were significantly higher than those before treatment （P<0.05），and the levels in observation group were significantly higher than those in control group （P<0.05）. There was no significant difference in the levels of serum interleukin-6 （IL-6），interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） before treatment. After treatment，the levels of serum IL-6，IL-1β and TNF-α were significantly lower than those before treatment （P<0.05），and the levels in observation group were significantly lower than those in control group （P<0.05）. Conclusion:On the basis of psychological intervention and paroxetine administration，the combination of Chaihu Shugansan and abdominal acupuncture exerts their respective advantages. It treats both symptoms and root causes of depression，relieves the degree of depression，reduces the classification of depression，and regulates the levels of neurotransmitter and cellular inflammatory factors，and inhibits inflammatory response. The clinical effect is significant.

The purpose of this research is to study the anti-atherosclerotic effects and mechanisms of berberine (BBR) in high fat diet (HFD) fed ApoE^-/- mice, and then to lay a solid foundation of the clinical studies of BBR treatment. The hyperlipidemic ApoE^-/- mice model was established by feeding HFD for 12 weeks. Mice were randomly divided into control group (chow diet), model group, BBR group (BBR-L: 50 mg·kg^-1, BBR-H: 150 mg·kg^-1) and atorvastatin (5 mg·kg^-1) group. Mice were intragastric administration with BBR in 0.5% sodium salt of caboxy methyl cellulose. After 12 weeks, enface aortas were stained with oil red O, and the lesions area were analyzed by Image J software. The inflammatory factor levels were detected by suspension microarray kits. Liver total cholesterol (TC), triglyceride (TG) and free fatty acids (FFA) were determined by commercial kits. Western blot was performed to examine the inflammatory pathway related and cholesterol and lipid transport related proteins' expression. All animal experiments were performed in accordance with the Regulation on the Administration of Laboratory Animals of Institute of Medicinal Biotechnology. After 12 weeks treatment, compared with model group, BBR treatment significantly reduced the lesions area of en face aortas and obviously inhibited serum proinflammatory factors such as IL-1β and IL-6 compared with model group. In addition, BBR treatment obviously reduced liver TC, TG and FFA levels compared with model group. Furthermore, mechanic study showed that BBR significantly inhibited MAPKs and NF-κB pathways, and increased cholesterol and lipid regulated proteins expression such as p-AMPK, LDLR, ABCA1 and SR-BI. In conclusion, BBR can obviously reduce enface aortas lesions in ApoE^-/- mice, which is related to inhibit inflammation and liver cholesterol and lipid accumulation.

Objective:To explore the influence of social-psychological factors on outcome of joint rehabilitation. Methods:From October, 2015 to April, 2017, 64 inpatients accepting joint rehabilitation were divided into anxiety group and non-anxiety group, and depression group and non-depression group, according to the scores of Hamilton Anxiety Scale and Hamilton Depression Scale. They were assessed with routine joint scores as initial and final stages of joint rehabilitation, as well as Symptom Checklist-90 (SCL-90) and World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0). The correlation of joint scores to scores of SCL-90 and WHO-DAS 2.0 was analyzed with Spearman correlation analysis. Results:There were significant differences in joint scores between the depression and the non-depression groups initially and finally (|t| > 2.106, P < 0.05). The joint score at the initial stage was negatively correlated with the interpersonal factor score of SCL-90 (r = -0.257, P < 0.05). The joint score at the final stage was negatively correlated (P < 0.05) with the dimension one (r = -0.257) and four (r = -0.278) of WHO-DAS 2.0, total score (r = -0.263), and interpersonal (r = -0.328) and hostile (r = -0.385) factor scores of SCL-90. Improvement of joint score negative correlated with dimension one of WHO-DAS 2.0 score (r = -0.249, P < 0.05). Conclusion:The social-psychological factors affect the outcome of joint rehabilitation. It is necessary to explore the way to take the the social-psychological assessment into the routine three stage evaluation of the joint rehabilitation protocol.

Objective To analysis the change of hip joint in healthy infants by ultrasound,and establish the normal reference value of the developmental dysplasia of the hip(DDH). Methods A total of 8 000 healthy infants from 0 to 24 weeks were collected from the Multi-center study of 10 children′s medical centers. Among them,3 855 infants(2 065 females and 1 790 males) with complete data and follow-up were included in this study. All subjects were divided into 6 groups ( ＜4,4～7,8～11,12～15,16～19 and≥20 weeks group). α angle,femoral head length and width,femoral head coverage ratio by acetabulum ( FHC) were measured in the coronal view on the neutral position;distance from pubis to femoral head ( P-H) and distance from ischium to femoral head ( I-H ) were measured in the transverse view on neutral position;distance from femoral head topubis ( H-P) was measured in the posterolateraltransverse view on the flexion position. The results of each group changes with age were analysised. Results ① The α angle of healthy infants from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05),but there was no significant difference between 16～19 and ≥20 weeks group( P ＞0.05). ②The femoral head length and width of all age groups were increased with age,the difference among all the groups was statistically significant( all P ＜0.05). ③ FHC from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05) except between 16～19 and ≥20 weeks group( P ＞0.05). ④ The P-H and I-H in all age groups showed no statistically significant ( all P＞0.05). ⑤The H-P of all age groups were increased with age,the difference between the groups were statistically significant(all P ＜0.05).Conclusions The development of hip joints have the certain regular developmental pattern in healthy infants less than 5 months of birth and are relatively constant after birth more than 5 months. The ultrasound normal reference value of the hip joints can be used for the early diagnosis of the DDH.

BACKGROUNDSepsis is a major cause of mortality in Intensive Care Units. Anesthetic dose isoflurane and 100% oxygen were proved to be beneficial in sepsis; however, their application in septic patients is limited because long-term hyperoxia may induce oxygen toxicity and anesthetic dose isoflurane has potential adverse consequences. This study was scheduled to find the optimal combination of isoflurane and oxygen in protecting experimental sepsis and its mechanisms.

METHODSThe effects of combined therapy with isoflurane and oxygen on lung injury and sepsis were determined in animal models of sepsis induced by cecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysaccharide (LPS) or zymosan. Mouse RAW264.7 cells or human peripheral blood mononuclear cells (PBMCs) were treated by LPS to probe mechanisms. The nuclear factor kappa B (NF-κB) signaling molecules were examined by Western blot and cellular immunohistochemistry.

RESULTSThe 0.5 minimum alveolar concentration (MAC) isoflurane in 60% oxygen was the best combination of oxygen and isoflurane for reducing mortality in experimental sepsis induced by CLP, intraperitoneal injection of LPS, or zymosan. The 0.5 MAC isoflurane in 60% oxygen inhibited proinflammatory cytokines in peritoneal lavage fluids (tumor necrosis factor-alpha [TNF-β]: 149.3 vs. 229.7 pg/ml, interleukin [IL]-1β: 12.5 vs. 20.6 pg/ml, IL-6: 86.1 vs. 116.1 pg/ml, and high-mobility group protein 1 [HMGB1]: 323.7 vs. 449.3 ng/ml; all P< 0.05) and serum (TNF-β: 302.7 vs. 450.7 pg/ml, IL-1β: 51.7 vs. 96.7 pg/ml, IL-6: 390.4 vs. 722.5 pg/ml, and HMGB1: 592.2 vs. 985.4 ng/ml; all P< 0.05) in septic animals. In vitro experiments showed that the 0.5 MAC isoflurane in 60% oxygen reduced inflammatory responses in mouse RAW264.7 cells, after LPS stimulation (all P< 0.05). Suppressed activation of NF-κB pathway was also observed in mouse RAW264.7 macrophages and human PBMCs after LPS stimulation or plasma from septic patients. The 0.5 MAC isoflurane in 60% oxygen also prevented the increases of phospho-IKKβ/β, phospho-IκBβ, and phospho-p65 expressions in RAW264.7 macrophages after LPS stimulation (all P< 0.05).

CONCLUSIONCombined administration of a sedative dose of isoflurane with 60% oxygen improves survival of septic animals through reducing inflammatory responses.

Adult ; Anesthesia ; methods ; Animals ; Blotting, Western ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Female ; Humans ; Inflammation ; drug therapy ; Isoflurane ; therapeutic use ; Leukocytes, Mononuclear ; metabolism ; Lipopolysaccharide Receptors ; metabolism ; Lipopolysaccharides ; pharmacology ; Lung Injury ; drug therapy ; immunology ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B ; metabolism ; Oxygen ; therapeutic use ; Peroxidase ; metabolism ; RAW 264.7 Cells ; Rats, Sprague-Dawley ; Sepsis ; drug therapy ; immunology ; Tumor Necrosis Factor-alpha ; metabolism