Objective To investigate the effects of proanthocyanidins on depressant-like behaviors and the structure of adrenal gland in chronic unpredictable mild stress (CUMS) rats. Methods Rats were randomly divided into 6 groups:control group, stressed group (CUMS + vehicle), three treatment groups (CUMS + proanthocyanidins 25,50,100 mg·kg-1,respectively) ,and imipramine group (CUMS + imipramine 10 mg·kg-1). Used the CUMS model in rats to investigate the effects of chronic oral administration (21 days) of proanthocyanidins and imipramine (ip) on the open-field;and forced swimming and sucrose consumption tests and the ratio of adrenal gland/body weight,and its thickness were examined by HE stain. Results Compared with control group, rats subjected to CUMS exhibited increased ratio of adrenal gland /body weight ( P < 0. 01), less sucrose consumption( P<0.01) and inhibited in the open-field test( P<0.01) as well as more despair time in the forced swimming test( P<0.01). While compared with stressed group,treatments with proanthocyanidins (25,50,100 mg·kg-1, po ,21 days) could significantly improve the activities in open-field test ((39.6±3.4) vs (49±4.5), (52.6±3.7),(54.1±1.8) ;all P<0.01) and sucrose consumption( (5.8±2.5)ml vs (8.1±3.3)ml,(8.5±4.1) ml, (9.2±2.6) ml; P < 0.05, P < 0.05, P < 0.01 respectively); Meanwhile, it could reduce the duration time in forced swimming test significantly( (103.5±10.2)s vs (83.7±8.8)s,(75.8±5.9)s,(67.2±6.5)s; all P<0.01) as well as thickness of the adrenal gland(P<0.05, P<0.01).Conclusions This study suggests that the proanthocyanidins (25,50,100 mg·kg-1) has an antidepressant-like effects in CUMS rats. The antidepressant actions of proanthocyanidins, in some degrees, may be related with the regulation of the adrenal gland's structure.

Objective To compare the dose distribution of postoperative plans with preoperative plans for 3D printing guide template assist radioactive seeds implantations,and explore the accuracy of treatment at dosimetry level.Methods A total of fourteen patients registered from Dec 2015 to Mar 2016 who were applied with 3D printing guide template assisted radioactive seed implantations in the hospital were included in this study.The preoperative planning design and 3D printing template production were performed for all patients.The dose related parameters including D90％,minimum peripheral dose (MPD),V100％,V150％,V200％,conformal index (CI),external index (EI),and homogeneity index (HI) were compared between pre-and post-operation.The paired t-test was used to perform the statistical analysis.Results A total of fourteen 3D printing individual templates were produced which included 16 treatment areas.Compared with preoperative plans,the mean value of V100％,Dg0％ and V150％ decreased while the mean value of V200％ and MPD increased in postoperative plans.However,there was no significant difference between the two groups except for V100％ (t =2.451,P ＜0.05).The differences of CI,EI,HI between two groups were not statistically significant (P ＞ 0.05).Conclusions The validation of actual dose distribution in postoperation assistied by 3D printing template in seed implantation shows that most of parameters could meet the expectation of preoperative plans,which indicates the improvement in accuracy for this new type of treatment.

Objective:To investigate the safety and effect of complete mesocolie excision (CME) combined with arterial infusion chemotherapy (AIC) and intra-peritoneal interstitial sustained-release chemotherapy (IPISRC). Methods:A total of 104 patients were classified under the experimental group and underwent CME combined with AIC and IPISRC. The other 98 patients were classified un-der the control group and only received radical surgery. Pre-and post-operative blood routine examinations, as well as liver and kidney function tests, were conducted for both groups. Post-operative adverse reactions and incidence of complications were recorded. Cancer and para-neoplastic tissues were sampled in experimental group. The post-surgery 5-fluorouracil (5-FU) concentration in the drainage fluid as well as those in the peripheral blood , were determined. Three-year follow-ups were conducted, during which the local recur-rence rate, liver metastasis, progression-free survival rate, and total survival rate were recorded. Results: No significant differences were found in the white blood cell count, hemoglobin count, liver and renal functions of the patients before and after the surgery, and rate of adverse reaction and complications between the two groups after surgery (P>0.05). In experimental group , the 5-FU concentra-tion was significantly higher in the cancer tissues than in the para-neoplastic tissues . The 5-FU concentration in experimental group was also significantly higher in the intra-peritoneal drainage liquid and reached its peak in the peripheral blood on day 3 post-surgery . Local recurrence and liver metastasis rates were significantly lower in experimental group than those in control group, whereas the pro-gression-free and three-year overall survival rates were significantly higher in experimental group than in control group (P<0.05). Con-clusion:The tharepy of pations of experimental goup is safe and effective. This method significantly improves the progression-free and three-year survival rates of the patients as well as significantly reduces the local recurrence and liver metastasis rates of colon cancer.

Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.

Objective:To compare the efficacy of sakubatril valsartan and valsartan in the treatment of patients with chronic cardiac insufficiency and the influence on zinc finger protein A20 and nuclear factor-κB (NF-κB) in peripheral bloodmononuclear cells (PBMCs).Methods:Ninety-senven patients with chronic cardiac insufficiency admitted to the Affiliated Hospital of Jining Medical College from February 2019 to January 2020 were continuously selected and randomly divided into the control group (48 cases) and the observation group (49 cases). Both groups received routine anti-heart failure according to the guidelines. The control group added with valsartan and the observation group added with sakubatril valsartan treatment. Before the treatment and after 3 months of treatment, the changes of cardiac function indexes and the changes of inflammatory markers such as hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP-9), and N-terminal pro B-type natriuretic peptide (NT-proBNP) were compared. PBMCs was extracted to detect zinc finger protein A20 and NF-κB levels. The incidence of adverse reactions in the two groups was recorded, and the relationship between zinc finger proteins A20, NF-κB and the myocardial injury marker NT-proBNP were analyzed.Results:After 3 months of treatment, the changes of cardiac function indexes in the observation group were better than those in the control group and the levels of hs-CRP, TNF-α, MMP-9, NT-proBNP in the observation group were lower than those in the control group: (1.96 ± 0.57) mg/L vs. (2.87 ± 0.79) mg/L, (7.11 ± 1.46) μg/L vs. (8.24 ± 1.57) μg/L, (110.14 ± 10.63) μg/L vs. (129.52 ± 17.96) μg/L, (716.91 ± 105.78) ng/L vs. (965.25 ± 97.41) ng/L, there were statistical differences ( P<0.05). After 3 months of treatment, the levels of finger protein A20, NF-κB in the observation group were lower than those in the control group: (3.57 ± 1.13) % vs. (4.41 ± 1.32) %, (29.87 ± 6.58) ng/L vs. (35.71 ± 10.02) ng/L, there were statistical differences ( P<0.05). Finger protein A20 and NF-κB in patients with chronic cardiac insufficiency were positively correlated with NT-proBNP ( r = 0.487, 0.738, P<0.01). Conclusions:On the basis of conventional treatment, compared with valsartan, the addition of sakubatril valsartan, can improve the cardiac function of patients with chronic cardiac insufficiency, reduce the body′s inflammatory response, reduce the expression of myocardial injury marker NT-proBNP, inhibit the activation of PBMCs NF-κB, and reduce the level offinger protein A20.

Immunosuppression plays a critical role in death of sepsis. Innate immunity is the first line defense to prevent pathogen invasion, and neutrophils, macrophages, dendritic cells and natural killer cells (NK cells) are closely involved in the process of the immune-regulation during sepsis. Recently, metabolic reprogramming in immune cells is known as a keystone for immune intervention therapy in sepsis. Here, we focus on the recent advances in metabolic regulation in neutrophils, macrophages, dendritic cells and NK cells including glycolysis, fatty acid synthesis, fatty acid oxidation and arginine metabolism involved in the immune-regulation of sepsis. This review will be helpful to summarize the mechanisms underlying sepsis-induced immunosuppression.

Objective:To analyze the application value of sakubatril valsartan in the treatment of chronic heart failure (CHF) based on cardiopulmonary test system.Methods:One hundred and thirty-five CHF patients admitted to the Affiliated Hospital of Jining Medical Collegefrom January 2019 to August 2020 were divided into the observation group (67 cases) and the control group (68cases) by random number table method. Both groups were treated with bisoprolol. The observation group was treated with the combination of sakubatril valsartan, and the control group was treated with the combination of benapril. The efficacy and cardiac function indicators of the two groups were compared. The cardiopulmonary exercise test system was used to measure the patient′s maximum exercise time (Tmax), maximum exercise Watt (Wmax), peak volume oxygen (Peak VO 2) and volume of anaerobic threshold oxygen (VO 2AT), and the incidence of adverse reactions were calculated. Results:The total effective rate in the observation group was higher than that in the control group: 92.54% (62/67) vs. 77.94%(53/68), the difference was statistically significant ( χ2 = 5.70, P<0.05). After the treatment, the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) in the observation group were lower than those in the control group: (2 000.47 ± 517.85) ng/L vs. (2 777.39 ± 812.49) ng/L, (0.33 ± 0.10) μg/L vs. (0.37 ± 0.09) μg/L, and the left ventricular ejection fraction (LVEF) was higher than that in the control group: (8.12 ± 6.44)% vs. (41.93 ± 6.73)%, the differences were statistically significant ( P<0.05). After the treatment, the left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left ventricular mass index (LVMI), left atrial volume index (LAVI) in the observation group were lower than those in the control group: (55.47 ± 6.93) mm vs. (62.00 ± 7.18) mm, (37.14 ± 6.36) mm vs. (41.35 ± 6.43) mm, (136.76 ± 7.13) mg/m 2 vs. (140.98 ± 7.47) mg/m 2, (28.23 ± 2.59) ml/m 2 vs. (31.98 ± 2.17) ml/m 2; the Tmax, Wmax, PeakVO 2 and VO 2AT in the observation group were higher than those in the control group: (619.08 ± 65.36) s vs. (58.70 ± 52.44) s, (142.96 ± 16.05) W vs. (124.19 ± 13.38) W, (20.00 ± 5.74) ml/(min·kg) vs. (18.13 ± 3.58) ml/(min·kg), (13.89 ± 3.69) ml/(min·kg) vs. (11.23 ± 2.36) ml/(min·kg), the differences were statistically significant ( P<0.05). However, there was no statistically significant in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Sakubatril valsartan in the treatment of CHF can not only optimize the efficacy and improve cardiac function, but also benefit cardiac exercise rehabilitation of patients, and not increase the safety risk.

Objective To investigate the effect of temperature on cell proliferation and osteogenic differentiation inhibition of preosteoblast induced by hydrogen peroxide(H2 O2).Methods The MC3T3-E1 cells in the logarithmic phase were randomly divided into 0,450,500,550,600,650 μmol·L-1 H2O2 intervention groups and incubated with 0,450,500,550,600,650 μmol·L-1 H2O2 for 2 h,respectively.Other MC3T3-E1 cells in the logarithmic phase were selected and randomly divided into the control group,model group,low-temperature group,and high-temperature group.Cells in the control group were cul-tured in an incubator with 5％CO2 for 24 h at 37 ℃;cells in the model group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 37 ℃;cells in the low-temperature group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 32 ℃;cells in the high-temperature group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 40 ℃.The cell proliferation in all groups was detected by cell counting kit-8.The expression levels of Runt-related transcription factor 2(RUNX2),osteopontin(OPN)and osteocalcin(OC)mRNA were detected by real-time fluorescence quantitave polymerase chain reaction;and the expression levels of RUNX2,OPN and OC protein were detected by Western blot.Results There was no statistically significant difference in cell proliferation among the 0,450 and 500 μmol·L-1 H2O2 intervention groups(P＞0.05);the cell proliferation rate in the 550,600 and 650 μmol·L-1 H2O2 intervention groups was significantly lower than that in the 0,450 and 500 μmol·L-1 H2O2 intervention groups,showing a significant decrease in cell proliferation with the increase of H2O2 concentrations(P＜0.05).In order to ensure that there were enough cells to perform the following experiments,550 μmol·L-1 H2 O2 was chosen.The cell proliferation rate in the model group and the low-temperature group was significantly lower than that in the control group and high-temperature group(P＜0.05);there was no significant difference in the cell proliferation rate between the control group and high-temperature group(P＞0.05).The relative expression of RUNX2 mRNA in the model group and high-temperature group were significantly higher than that in the control group and low-temperature group(P＜0.05);the relative expression of RUNX2 mRNA in the low-temperature group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the relative expression of RUNX2 mRNA between the model group and high-temperature group(P＞0.05).The relative expression of OPN mRNA in the model group,low-temperature group and high-temperature group was significantly higher than that in the control group(P＜0.05);the relative expression of OPN mRNA in the low-temperature group and high-temperature group was significantly higher than that in the model group(P＜0.05);the relative expression of OPN mRNA in the low-tem-perature group was significantly higher than that in the high-temperature group(P＜0.05).The relative expression of OC mRNA in the model group,low-temperature group and high-temperature group was significantly than that in the control group(P＜0.05);the relative expression of OC mRNA in the low-temperature group and high-temperature group was significantly higher than that in the model group(P＜0.05);there was no significant difference in the relative expression of OC mRNA between the low-temperature group and high-temperature group(P＞0.05).The relative expressions of RUNX2,OPN and OC protein the model group,low-temperature group and high-temperature group were significantly lower than those in the control group(P＜0.05);the relative expressions of RUNX2 and OPN protein in the low-temperature group were significantly lower than those in the model group and high-temperature group(P＜0.05);the relative expression of OC protein was significantly lower than that in the high-temperature group(P＜0.05);and there was no siqnificantly difference in the relatiwe experesson of OC protein between the low-temperature group and model group(P＞0.05);the relative expressions of RUNX2,OPN and OC protein in the high-temperature group were significantly higher than those in the model group(P＜0.05).Conclusion The inhibitory effects of H2O2 on cell proliferation and osteogenic differentiation are observed in MC3T3-E1 cells;low-tempera-ture incubation can enhance the inhibition of H2O2 on cell proliferation and osteogenic differentiation in MC3T3-E1 cells,while high-temperature incubation can relieve its inhibitory effect on cell proliferation and osteogenic differentiation.RUNX2,OPN and OC protein might play an important role in cell proliferation and osteogenic differentiation mediated by temperature.

Objective To analyze clinical characteristics of severe community-acquired pneumonia during pregnancy and its outcomes, and to explore the relevant risk factors. Methods From September 2012 to September 2017,324 398 pregnancies admitted in 7 tertiary hospitals were included. Clinical data of 33 cases of pregnancies with severe community-acquired pneumonia(severe pneumonia group)and 214 cases of pregnancies with common community-acquired pneumonia (control group) were reviewed retrospectively, including the clinical information, manifestations, laboratory examinations and pregnancy outcomes. Relevant risk factors were analyzed by multivariate logistic regression analysis. Results (1) General data: pregnancies with severe community-acquired pneumonia accounted for 0.010%(33/324 398) of hospitalized pregnancies, the gestational age of two groups were(28±8)and(23±8)weeks, body mass index were(21.7±2.1)and(25.5±3.4)kg/m2, rate of low income were 54.5%(18/33)and 31.8%(68/214), respectively. The differences between two groups were all statistically significant(all P<0.05). No significant differences were found in age, pregnancy and parity times, rate of main pregnant complications such as diabetes and hypertension, educational level, asthma and onset seasons between two groups(all P>0.05). (2)Clinical data: the severe pneumonia group had significantly higher incidence of fever [100.0%(33/33)vs 75.2%(161/214)], shortness of breath(90.9% vs 16.8%)compared with the control group(all P<0.05).The median peripheral leukocytes counts were 12.3×109/L and 10.2×109/L, the hemoglobin level were(84±18) and(107±14)g/L,the albumin level were(26±4)and(37±3)g/L, the median serum urea nitrogen level were 3.7 and 2.4 mmol/L,the serum creatinine level were(72±25)and(45±11)μmol/L, respectively in two groups. The differences were all statistically significant (all P<0.05). No significantly statistical differences were found in coagulation indicator and cardiac function between two groups(all P>0.05).(3) Treatments: in severe pneumonia group, 12 patients(36.4%,12/33)needed invasive mechanical ventilation, 9 patients(27.3%,9/33)needed non-invasive mechanical ventilation, average time of mechanical ventilation was(7±4)days;8 patients(24.2%,8/33)with septic shock needed vasoactive drugs. However, there was no patient in control group needing mechanical ventilation and vasoactive drugs.(4)Pregnant outcomes: one patient(3.0%,1/33)died in the severe pneumonia group, while no death occurred in the control group. The hospital stay between two groups were(15.1±4.1)and(7.0±1.9)days, the rates of abortion and stillbirth between two groups were 42.4%(14/33)and 3.3%(7/214), the rates of premature were 10/19 and 6.3% (13/207), the rates of cesarean were 15/19 and 43.0%(89/207), the rates of low birth weight newborn were 17/19 and 14.0%(29/207), the rates of infected newborn were 15/19 and 10.1%(21/207), the birth weights were(2 165±681)and(3 102±400)g, respectively. The differences between two groups were all statistically significant(all P<0.05).(5)Multivariate logistic regression analysis demonstrated that anemia, low body mass index, hypoproteinemia were risk factors for severe pneumonia in pregnancy(all P<0.05). Conclusions Pregnancy with severe community-acquired pneumonia may be complicated by multiple organ dysfunctions, lead to adverse outcomes. Anemia, malnutrition are risk factors for pregnancy with severe pneumonia. Active and effective treatment may improve its prognosis.

Objective:To evaluate the clinical efficacy and safety of a skin care ointment containing oligomeric maltose X in the adjuvant treatment of eczema-related pruritus.Methods:A multicenter, randomized, double-blind, vehicle-controlled clinical study was conducted. From March to September 2021, outpatients with mild to moderate eczema were collected from departments of dermatology of 4 hospitals, including Beijing Friendship Hospital, Hebei Traditional Chinese Medical Hospital, the Third People′s Hospital of Hubei Province, and Taizhou Central Hospital in Zhejiang Province. The patients were randomly divided into two groups by using a random number table: observation group topically treated with a skin care ointment containing oligomeric maltose X, and vehicle control group topically treated with an ointment vehicle. The ointments were applied during the attacks of itching for 14 consecutive days. Visits were scheduled before, 7, and 14 days after the start of the adjuvant treatment. The efficacy was evaluated according to the eczema area and severity index (EASI) and visual analog scale (VAS) , and adverse events were recorded. The efficacy and safety analyses were conducted by using chi-square test and t test. Results:Totally, 232 patients with eczema were enrolled, including 90 males and 142 females, with the age being 40.13 ± 13.36 years; 156 patients were in the observation group, and 76 in the vehicle control group. Before the adjuvant treatment, there were no significant differences in EASI (2.07 ± 2.24 points vs. 2.29 ± 2.28 points) or VAS (6.22 ± 1.78 points vs. 6.20 ± 1.79 points) scores between the observation group and vehicle control group ( t = -0.70, 0.06, P = 0.486, 0.955, respectively) . After one-day treatment, the VAS scores significantly decreased compared with the baseline scores in the two groups ( P < 0.001, P = 0.003, respectively) . After 14-day treatment, the VAS score was significantly lower in the observation group (2.67 points) than in the vehicle control group (3.35 points; t = -2.28, P = 0.024) . After 7- and 14-day treatment, the EASI scores significantly decreased compared with the baseline scores in both the two groups (all P < 0.001) , but there were no significant differences between the two groups ( P = 0.853, 0.731) . No adjuvant treatment-related adverse events were recorded in either of the two groups. Conclusion:The skin care ointment containing oligomeric maltose X is safe and effective in the adjuvant treatment of eczema-related pruritus, and can be applied to clinical practice.