Objective To discuss the correlations between hemoperfusion(HP) times and therapeutic effects/prognosis in patients with severe acute organophosphorus poisoning(AOPP). Methods According to the frequency of HP,82 patients with severe AOPP were divided into three groups:non HP(25 cases),HP1(27 cases) and HP2(30 cases)groups. The non HP group received only routine treatment,on the basis of routine treatment,the HP1 group accepted once HP within 12 hours after poisoning and the HP2 group underwent twice or more times of HP,the interval between each time being 24 hours. The comparisions of clinical indexes,incidences of complications and rates of mortality among the three groups were performed. Results With the increase of HP times,the dosages of atropine and pralidoxime chloride were significantly reduced,the times of serum cholinesterase(ChE)activity recovery,consciousness recovery,hospitalization and mechanical ventilation were significantly shortened,the score of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score in 48 hours after admission,incidence of complications and mortality were evidently decreased(all P<0.05). Compared with those in HP1 group,the dosages of atropine(mg:164.57±68.82 vs. 256.81±97.06)and pralidoxime chloride(mg:6.95±1.40 vs. 8.76±1.64) in HP2 group were significantly reduced,the times of ChE activity recovery(day:9.03±2.46 vs. 10.96±3.44), consciousness recovery(hour:23.83±6.29 vs. 39.93±8.24),hospitalization(hour:9.57±2.39 vs. 11.52±3.02) and mechanical ventilation(hour:40.50±16.55 vs. 65.74±18.88)in HP2 group were significantly shortened;APACHEⅡscore during 48 hours after admission(11.97±3.47 vs. 14.26±2.88)was obviously decreased,and the incidences of complications,such as intermediate syndrome(10.0% vs. 18.5%),rebound phenomenon(3.3% vs. 25.9%),arrhythmia(13.3%vs. 44.4%),multiple organ dysfunction syndrome(MODS,6.7%vs. 29.6%)and mortality rate(6.7% vs. 18.5%)in HP2 group were markedly decreased(all P<0.05). Conclusion It is recommendable that combined with routine treatment,early and multiple HP application would enhance the therapeutic effect and decrease the mortality in patients with severe AOPP.

AIM:To observe the effects of normal mesenteric lymph (NML) on the lung, heart and liver inju-ries and the phosphorylation levels of p 38 mitogen-activated protein kinase ( MAPK) , extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) in the mice with endotoxic shock (ES).METHODS: The NML was drained form health male BALB/c mice for the intervention of ES after the removal of cellular constituent .Lipopolysaccha-ride (LPS, 35 mg/kg) was intraperitoneally injected into the mice for the establishment of ES model .After 60 min of LPS injection, the administration of NML (1/15 of whole blood volume) was performed through the femoral artery in NML +ES group.Meanwhile, the mean arterial pressure (MAP) was monitored during the experiment .At 6 h after intraperitoneal in-jection of LPS or the corresponding time point , blood samples were harvested from the heart through apical centesis for de-termination of the biochemical indexes to reflect myocardial and hepatocyte injuries .Simultaneously , the lung , heart and liver tissue specimens from a fixed location were harvested for the observation of histomorphology and the measurement of phosphorylation levels of p38 MAPK, ERK1/2 and JNK.RESULTS:Compared with sham shock (SS) group, MAP in ES group and NML+ES group remarkably decreased at multiple time points after intraperitoneal injection of LPS .However, MAP in NML+ES group at 80 min, 90 min, 190 min, 210 min, 240 min, 250 min, 340 min, 350 min, and 360 min were significantly increased compared with ES group .There were normal structures in the lung , liver and myocardium of the mice in SS group, while the morphological damages of these tissues appeared in ES group .Meanwhile, the damages were attenuated in the mice of NML +ES group.The activities of AST , ALT and CK-MB in the plasma in ES group were remark-ably higher than those in SS group .The CK-MB activity in NML+ES group was also increased compared with SS group , and the activities of AST and LDH-1 were lower than those in ES group .At 6 h after LPS injection , the phosphorylation levels of p38 MAPK, ERK1/2 and JNK in the lung tissues were remarkably increased .Meanwhile , no statistical difference of these indexes between the myocardial and hepatic tissues was observed .NML intervention decreased the phosphorylation levels of p38 MAPK in the lung tissues , and p38 MAPK, ERK1/2 and JNK in the myocardial tissues .CONCLUSION:The NML administration alleviates multi-organ injuries and reduces the phosphorylation level of p 38 MAPK in the lung tis-sues in the mice subjected to ES .

BACKGROUND:Tissue-engineered bone scaffold fabricated by 3D-bioprinting technique has good controlability in morphology and structure. However, construction of tissue-engineered bone/cel growth factor complex and time-dose effect of sustained-release factors are needed to be further researched.
OBJECTIVE:To fabricate a sustained-release composite of polylactic-co-glycolic acid (PLGA)/nano-hydroxyapatite (n-HA) scaffold carrying bone morphogenetic protein-2 (BMP-2) using 3D-bioprinting technique, and test the biological properties of the PLGA/n-HA scaffold carrying BMP-2 and the sustained-release properties, thereby to discuss its feasibility as the tissue-engineered bone scaffold composite.
METHODS:Temperature-sensitive chitosan hydrogel was prepared using chitosan andβ-glycerophosphate to construct a sustained-release composite, chitosan nanoparticles carrying BMP-2 . 3D-bioprinting technique was utilized to fabricate the PLGA/n-HA scaffold carrying BMP-2. Biological features of the scaffold composite were tested, and time-dose effect of BMP-2 sustained-release was observed.
RESULTS AND CONCLUSION:The average pore size of the scaffold-cytokine composite was (431.31±18.40)μm, and the porosity was (73.64±1.82)%. The cumulative release rate of BMP-2 from the scaffold-cytokine composite that effectively controled the burst release during 48 hours and 30 days were suitable for the physiological needs. In conclusion, the porosity, pore size, release property, degradation rate, and mechanical strength of the scaffold-cytokine composite al meet the biological requirements of tissue-engineered bone construction.

BACKGROUND:J2 takes functional domain (MHC CD4-D1/) of complex conjugate of CD4 molecule and MHC class II molecule as a target, and is a smal molecule compound obtained by computer screening from a chemical data containing hundreds of thousands of organic compounds. In the previous study, J2 was used in mouse models of skin transplantation and keratoplasty by oral and intraperitoneal injection. Results verified that J2 could prolong the survival time of grafts, and suppress occurrence of rejection. To better play the role of a drug targeting and to reduce systemic toxicity, J2 wil be further utilized in local treatment of keratoplasty rejection. OBJECTIVE:To investigate the inhibitory effect of new immunosuppressive agent J2 on CD4+ and CD8+T cel immune functions in rat models receiving alogenic penetrating keratoplasty. METHODS:Alogeneic penetrating keratoplasty model was established using the adult female Wistar rats as donors and Sprague-Dawley rats as recipients. Group A: normal Sprague-Dawley rats were injected with 0.05 mL placebo subconjunctivaly. Surgery rats were randomly divided into three groups. Group B: alograft rats were injected with 0.05 mL placebo subconjunctivaly after autologous keratoplasty. Group C: alograft rats were injected with 0.05 mL placebo subconjunctivaly. Group D: alograft rats were injected with 1% J2-nanosuspension 0.05 mL subconjunctivaly. The distribution of T cel subsets in peripheral blood was detected using flow cytometry at 3 days, 1, 2 and 3 weeks after transplantation and compared among groups. RESULTS AND CONCLUSION: There was no significant difference in total CD3+ T cels, CD4+ T cels, CD8+ T cels and CD4+/CD8+ in peripheral blood lymphocytes in group B at various time points. At 3 days and 1 week after surgery in group C, no significant difference in total CD3+ T cels, CD4+ T cels and CD8+ T cels was detected. At 1 and 2 weeks, the number of total CD3+ T cels, CD4+ T cels and CD8+ T cels increased, showing significant differences (P < 0.05). In group D, no significant hyperplasy was found in CD4+ T cels and CD8+ T cels at 1 and 2 weeks. The horizontal comparison of the same time point: the total CD3+ T lymphocytes of group D was significantly less than group C at 3 days, 1 and 2 weeks after operation (P < 0.05), whereas there was no significant difference at 3 weeks between the group D and group C. The number of CD4+ T lymphocytes in group D was less than in group C at 3 days and 1 week, but with no significant difference. The ratio of CD4+/CD8+ had no significant difference in group D compared with group C at 3 days, 1 and 3 weeks. J2 inhibits T lymphocyte proliferation and then inhibits T cel-mediated corneal alograft rejection.

Objective:To observe the protective effect of deproteinized extract of calf blood (DECB) on the kidney injury of the diabetic rats, and to discuss its mechanism preliminarily.Methods:The male Wistar rats were intraperitoneally injected with STZ (65 mg·kg-1) to establish the diabetes models, then the model rats were randomly divided into model (M)group, and metformin (MMet, 105 mg·kg-1) group , low dose of combined administration (ML,105 mg·k-1 metformin+94.5 mg·kg-1 ,DECB) group, medium dose of combined administration(MM, 105 mg·kg-1 metformin+ 189 mg·kg-1 DECB) group, high dose of combined administration(MH, 105 mg·kg-1 metformin +378 mg·kg-1,DECB) group, another ten Wistar rats were selected as normal control(NC)group.The rats were intragastrically administed with metformin and intraperitoneally injected with DECB, once a day, total of 8 weeks.The rats in NC group and M group were given normal saline solution.The weights and blood glucose levels of the rats in various groups were determined;the levels of serum high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), blood urea nitrogen (BUN), urinary albumin (UAlb), urine creatinine (UCR), serum creatinine (SCr), total cholesterol (TC), triglyceride (TG), uric acid (UA), glutathione (GSH), and malondialdehyde (MDA) were detected;the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined.The pathological changes of kidney tissue of the rats in various groups were detected by HE staining.Results:Compared with NC group, the weight of the rats in M group was reduced(P<0.05),and the levels of blood glucose,UAlb,UCr,SCr,UA,BUN,LDL-C,TC,TG,and MDA were increased(P<0.05);the levels of HDL-C and GSH were obviously reduced(P<0.05),and the activities of SOD adn GSH-Px were obviously reduced(P<0.05).Compared with M group,the weights of the rats in MM and MH groups were increased (P<0.05), and the levels of blood glucose,UAlb,UCr,SCr,UA,BUN,LDL-C,TC,TG, and MDA were decreased (P< 0.05);the levels of HDL-C and GSH were increased (P<0.05),and the activities of SOD and GSH-Px were increased (P<0.05).The pathological observation of kidney tissue showed that the rats in M group had obvios kidney tissue lesions with glomerular congestion and renal tubular edema compared with NC group;compared with M group,the pathological changes of the kidney tissue of the rats in drug administration groups were significantly improved, the renal tubular vacuoles were reduced, and the interstitial hyperplasia was not obvious.Conclusion:DECB combined with metformin can reduce the blood glucose level, regulate blood lipid, improve the pathological changes of kidney tissue in the diabetic rats, reduce the renal damage, and enhance the antioxidant capacity of the body.

Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.

Objective:To observe the protective effect of deproteinized extract of calf blood (DECB)on the ethanol-induced liver injury of the mice,and to preliminaryly discuss its mechanism. Methods:Sixty healthy ICR mice were divided into control group,model group,positive drug group,low,medium and high doses of DECB groups (n=10).By intragastric administration,the mice in control group were given 20 mL·kg-1 saline solution, the mice in low,medium and high doses of DECB groups were administrated with 0.125,0.250,0.500 g·kg -1 DECB,and the mice in positive drug group were administrated with 0.63 g·kg -1 Hugan Tablets;once a day for 30 d. 1 h after the last administration,except control group,the mice in other groups were administrated with one-time grant of 50% ethanol 14 mL·kg -1 ,and fasted for 16 h to establish the models of acute alcohol liver injury.The endurance alcohol time and drunk time of the mice were determined,the activities of aspartate aminotransferase (ALT)and alanine transaminase (AST)activity in serum of the mice were detected,the levels of triglyceride (TG),glutathione (GSH)and malonic dialdehyde (MDA)in liver tissue were determined,and the pathological changes of liver tissue were detected.Results:Compared with model group,the drunk symptoms of the mice in different doses of DECB groups were obviously reduced,the endurance time of the mice in high dose of DECB group and positive drug group was prolonged (P <0.05),and the drinking time was shortened (P <0.05);the ALT and AST activities in serum in mediun and high doses of DECB groups were significantly lower than those in model group (P <0.05).Compared with model group,the MDA and TG levels in liver tissue of the mice in medium and high doses of DECB groups and positive drug group were obviously reduced,and the GSH levels were increased (P <0.05);compared with model group,the pathological damages of liver tissue of the mice in high dose of DECB group caused by ethanol were significantly reduced.Conclusion:DECB can improve ethanol-induced liver injury which may be related to the inhibition of hepatic oxidative stress response.

Objective To explore the preoperative predictors of lymphovascular invasion(LVI)in patients with advanced gastric cancer,and establish the corresponding nomogram prediction model and conduct internal validation.Methods A total of 246 cases of advanced gastric cancer who underwent surgical resection in the Department of Gastrointestinal Surgery of Hengshui People's Hospital from January 2018 to December 2021 were selected.Patients were divided into the LVI positive group and the LVI negative group according to postoperative pathological diagnosis.The age,gender,tumor differentiation,tumor size,tumor site,Borrmann classification,Lauren's classification,cT stage,cN stage and systemic immune-inflammation index(SII)of patients were collected and compared between the two groups.The predictors that were statistically different between the two groups were subjected to multivariate Logistic regression and further developed into a visual prediction model.Bootstrap method was applied for internal validation of the prediction efficiency of the model.Results The differences of tumor size,Borrmann classification,tumor differentiation,Lauren classification,cT staging,cN staging and SII were statistically significant between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that tumor size(OR=2.184,95%CI:1.224-3.898),Borrmann classification(OR=2.517,95%CI:1.294-4.896),cT staging(OR=1.860,95%CI:1.045-3.308),cN staging(OR=1.816,95%CI:1.004-3.285)and SII(OR=1.001,95%CI:1.000-1.002)were independent predictors of LVI in advanced gastric cancer.A preoperative nomogram prediction model for advanced gastric cancer LVI was developed based on results of multivariate analysis.By internal validation,the area under curve(AUC)value of the subject operating characteristic(ROC)curve of the nomogram was 0.735,which was higher than that of tumor size(0.599),Borrmann staging(0.564),cT staging(0.604),cN staging(0.582)and SII(0.615),respectively.The calibration curve showed that the probability of predicted LVI by the nomogram was in a good agreement with the probability of actual LVI occurrence.The Hosmer-Lemeshow test showed good model fit(χ2=4.387,P=0.821).Conclusion The established nomogram prediction model can help to predict the probability of LVI in advanced gastric cancer preoperatively,which can provide a guideline for clinical individualized treatment.

Objective To study doctor-patient interest demands satisfaction and its influencing factors of the payment system reform of the new rural cooperative medical care scheme to provide reference for the reform. Methods Cross-sectional survey was conducted from September 2016 to February 2017. Multi-stage stratified random sampling was used in six counties of three provinces in the eastern, middle and western regions of China, and mathematical statistics was applied to analyze the data. Results The doctor-patient overall interest demands satisfaction was high, but the satisfaction was lower both with the income and ability improvement of medical staff and with the benefits of farmers. The influencing factors of the satisfaction of managers in medical institutions included the type of payment, educational level and work unit (P＜0.05). The influencing factors of medical staff's satisfaction included the type of payment, work unit, and working years among others(P＜0.05). The influencing factors of farmers'satisfaction included the type of payment and the average annual income, etc(P＜0.05). Conclusions The core interest demands of both doctors and patients should be valued to enhance their satisfaction. Diseases related groups should be promoted and applied scientifically, and appropriately integrated with other methods of payment. Both doctors and patients'understanding of the payment reform should be improved by propaganda and training, to get their support and cooperation.

Objective: To study the best time of early feeding in patients with acute oral organophosphorus pesticide poisoning. Methods: A prospective study was conducted on 123 patients with acute oral organophosphorus poisoning admitted from January 2018 to May 2019 in Department of Emergency, the Affiliated Hospital of Binzhou Medical University. The patients were divided into four groups, A(<6 h), B(≥6 h-<12 h), C(≥12 h-<24 h) and D(≥24 h), according to the time of poisoning at the time of admission. All the patients in the four groups were fed immediately upon admission with the same method. The cholinesterase activity at 24, 48, 72, 120 h after poisoning, the incidence of rebound after poisoning, the disappearance time of clinical poisoning symptoms were compared among the four groups. Results: Compared with the other three groups, group A had a statistically significant difference in the cholinesterase activity at 24, 48, 72, 120 h after poisoning (H value was 9.466-24.933, P<0.05 or 0.01). There was no significant difference between the two groups in B, C, D group (P>0.05). The incidence of rebound after poisoning in A, B, C, D group was 3.448%(1/30), 7.407%(2/29), 6.452%(2/33), 6.897%(2/31), respectively, with no statistically significant difference (χ² value was 0.431, P>0.05). Compared with the four groups, the disappearance time of clinical poisoning symptoms in group A was shorter than that in the other three groups, and the difference was statistically significant (H value was18.199, P<0.05). Conclusions The earlier the patients ate, the faster the recovery of cholinesterase activity, the earlier the improvement of poisoning symptoms, and the incidence of gastrointestinal reaction and rebound after poisoning is not increased.The best time for early feeding is less than 6 h after poisoning.