Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Background:In the clinical setting, the effect of intra-abdominal hypertension on the human body is dependent on time, but its role is not yet clear.Objective:To investigate the effect of the duration of intra-abdominal hypertension (IAH) on the prognosis of critically ill patients.Methods:This prospective cohort study enrolled 256 IAH patients who were admitted to the Surgical ICU of 10 Grade A hospitals in Fujian Province from January 2018 to December 2020. The duration of IAH (DIAH) was obtained after monitoring IAP, and ICU length of stay, duration of mechanical ventilation, duration of continuous renal replacement therapy (CRRT) and average daily energy intake from enteral nutrition during ICU stay were observed and recorded. The correlation was analyzed by Spearman rank correlation. The patients were divided into the survival group and the death group according to their survival state at 60 days after enrollment. Thereafter, clinical characteristics between the two groups were compared. Multivariable logistic regression was used to study and validate the relationship between DIAH and 60-day mortality. The receiver operating characteristics (ROC) curve was established to evaluate the predictive abilities of DIAH on the mortality risk.Results:In critically ill patients, DIAH was positively correlated with duration of mechanical ventilation ( r=0.679, P<0.001), duration of CRRT ( r=0.541, P<0.001) and ICU length of stay ( r=0.794, P<0.001), respectively. In addition, there was a negative correlation between DIAH and average daily energy intake from enteral nutrition ( r=-0.669, P<0.001). After multivariable adjustment, DIAH was an independent risk factor for 60-day mortality in critically patients with IAH ( OR=1.05, 95% CI: 1.01-1.12; P = 0.012), and exhibited a linearity change trend relationship with mortality risk. The ROC curve analysis of DIAH showed that the area under ROC curve (AUC) was 0.825 (95% CI: 0.763~0.886, P<0.01). When the cut-off value was 16.5 days, the sensitivity was 78.4% and the specificity was 75.4%. Conclusions:DIAH is an important risk factor for prognosis in critically ill patients. Early identification and rapid intervention for the etiology of IAH should be performed to shorten DIAH.

Objective:To investigate the clinical efficacy and prognostic influencing factors of open abdomen technique for acute pancreatitis with abdominal compartment syndrome (ACS).Methods:The retrospective cohort study was conducted. The clinical data of 186 patients of acute pancreatitis with ACS who were admitted to 6 hospitals, including 65 cases in the 910th Hospital of Joint Logistics Support Force of Chinese People′s Liberation Army, 46 cases in the First Affiliated Hospital of Wenzhou Medical University, 33 cases in the Fujian Provincial Hospital, 31 cases in the Second Affiliated Hospital of Fujian Medical University, 7 cases in the People′s Hospital Affiliated to Quanzhou Medical College, 4 cases in the Shishi General Hospital, from January 2013 to December 2020 were collected. There were 142 males and 44 females, aged (43±8)years. Observation indica-tors: (1) patients conditions after being treatment with open abdomen technique; (2) analysis of clinical characteristics in patients with different treatment outcomes; (3) changing trend of the volume of urine output, levels of lactic acid, levels of enteral nutrient intake and the sequential organ failure score in patients with different treatment outcomes; (4) influencing factors for prognosis of patients. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test or the continuity correction chi-square test. Repeated measurement data were analyzed using the repeated ANOVA. Spearman correlation analysis was used for correlation analyses. The COX regression model was used for univariate analysis and COX regression model with forward regression was used for multivariate analysis. Results:(1) Patients conditions after being treatment with open abdomen technique. Intra-abdominal pressure, oxygena-tion index, levels of lactic acid and sequential organ failure score of the 186 patients were (23.3±1.9)mmHg (1 mmHg=0.133 kPa), (121±24)mmHg, (5.0±3.4)mmol/L and 10.4±3.6 before the treatment with open abdomen technique and (11.2±2.9)mmHg, (222±38)mmHg, (3.2±2.1)mmol/L and 4.4±2.3 at postoperative 168 hours, showing significant differences in time effects before and after the treatment ( Ftime=855.26,208.50, 174.91,208.47, P<0.05). (2) Analysis of clinical characteristics in patients with different treatment outcomes. Of the 186 patients, 166 cases survived and were discharged, and 20 cases died during hospitalization. Age, sequential organ failure score, duration of ACS and levels of lactic acid during hospitalization before the treatment with open abdomen technique were (41±7)years, 9.4±3.4, 13(10,21)hours and (4.2±0.6)mmol/L in surviving patients, versus (45±6)years, 11.5±2.4, 65(39,84)hours and (5.2±0.5)mmol/L in dead patients, respectively, showing significant differences between them ( t=-2.10, -2.71, Z=-5.36, t=-7.16, P<0.05). Duration of postoperative acute gastro-intestinal injury, duration of continuous renal replacement therapy, time to liberation from mech-anical ventilation, duration of vasoactive drugs therapy, cases undergoing early abdominal closure, cases without intestinal fistula or with postoperative high-order intestinal fistula and low-order intestinal fistula during hospitalization after the treatment with open abdomen technique were 4(2,6)days, 4(3,7)days, 34(21,41)days, 3(2,6)days, 126, 131, 23, 12 in surviving patients, versus 13(10,17)days, 10(8,18)days, 0(0,3)days, 8(6,12)days, 1, 2, 15, 3 in dead patients, respectively, showing significant differences between them ( Z=-5.60, -3.75, -3.64, -3.06, χ2=41.43, 45.86, P<0.05). (3) Changing trend of the volume of urine output, levels of lactic acid, levels of enteral nutrient intake and the sequential organ failure score in patients with different treatment outcomes. The volume of urine output, levels of lactic acid, levels of enteral nutrient intake and the sequential organ failure score in surviving patients during hospitalization were (0.29±0.10)mL/(kg·h), (4.2±0.6)mmol/L, 0.0 kcal/(kg·d) and 9.4±3.4 before the treatment with open abdomen technique and (2.22±0.15)mL/(kg·h), (1.9±0.7)mmol/L, (20.7±2.9)kcal/(kg·d) and 3.7±2.2 at postoperative 168 hours. The above indicators in dead patients during hospitalization were (0.28±0.08)mL/(kg·h), (5.2±0.5)mmol/L, 0.0kcal/(kg·d) and 11.5±2.4 before the treatment with open abdomen technique and (0.28±0.09)mL/(kg·h), (7.7±0.8)mmol/L, (4.6±1.8)kcal/(kg·d) and 12.4±2.1 at postoperative 168 hours. There were significant differences in time effects in the above indicators in surviving patients and dead patients before and after the treatment with open abdomen technique ( Ftime=425.57, 188.59, 394.84, 37.52, P<0.05). There were interactive effects between the above indicators and the treatment outcome at different time points ( Finteraction=383.14, 233.04, 169.83, 36.61, P<0.05). There were signifi-cant differences in the change trends of the above indicators between the surviving patients and the dead patients during hospitalization ( Fgouprs=2 739.56, 877.98, 542.05, 240.85, P<0.05). (4) Influen-cing factors for prognosis of patients. Results of univariate analysis showed that age, sequential organ failure score, duration of ACS before surgery, procalcitonin, lactic acid, postoperative high-order intestinal fistula, abdominal hemorrhage, duration of postoperative acute gastrointestinal injury, duration of continuous renal replacement therapy, duration of vasoactive drugs therapy, early abdominal closure were related factors influencing prognosis of patients under-going treatment with open abdomen technique ( hazard ratio=1.07, 1.18, 1.39, 1.16, 8.25, 12.26, 2.83, 1.29, 1.56, 1.41, 0.02, 95% confidence interval as 1.00-1.15, 1.45-2.27, 1.22-1.57, 1.02-1.32, 1.75-38.90, 7.37-41.23, 1.16-6.93, 1.22-1.37, 1.23-1.99, 1.08-1.84, 0.00-0.16, P<0.05). Results of multivariate analysis showed that extended duration of ACS before surgery, postoperative high-order intestinal fistula and extended duration of postoperative acute gastrointestinal injury were independent risk factors influencing prognosis of patients undergoing treatment with open abdomen technique ( hazard ratio=1.05, 7.95, 1.17, 95% confidence interval as 1.01-1.32, 2.05-30.87, 1.13-1.95, P<0.05) and early abdominal closure was an independent protective factor ( hazard ratio=0.10, 95% confidence interval as 0.01-0.89, P<0.05). Results of Spearman correlation analysis showed that duration of ACS was positively correlated with sequential organ failure score before surgery ( r=0.71, P<0.05). Conclusions:Open abdomen technique is effective for acute pancreatitis with ACS. Extended duration of ACS before surgery, postoperative high-order intestinal fistula and extended duration of postoperative acute gastrointestinal injury are independent risk factors for prognosis of patients during hospitalization and early abdominal closure is an independent protective factor.

Objective:To explore the effect of electromyography biofeedback therapy combined with oxiracetam on peripheral blood heme oxidase-1 (HO-1), soluble apoptotic molecules and cognitive function in patients with senile vascular dementia (VaD).Methods:One hundred and fourteen elderly patients with VaD from May 2018 to May 2020 in Xingtai Third Hospital were selected and divided into two groups according to the random number table method, with 57 cases in each group. Both groups were given conventional treatment. On this basis, the control group was given oxiracetam, and the observation group was given electromyography biofeedback therapy combined with oxiracetam. The treatment effects after treated for 1 month was compared between the two groups. The levels of serum HO-1, soluble apoptotic molecules sFas, sFasL before and after treatment were compared between the two groups. Cognitive function evaluated by Wechsler Memory Scale (WMS), Mini Mental State Examination (MMSE). The scores of Chinese Stroke Scale (CSS), Ability of Daily Living (ADL) before and after treatment and adverse reactions were compared between the two groups.Results:After treated for 1 month, the total effective rate in the observation group was higher than that in the control group: 93.0%(53/57) vs. 77.2%(44/57), the difference was statistically significant ( P<0.05). After treated for 1 month, the level of serum HO-1 in the two groups was higher than that before treatment, and the level of serum HO-1 in the observation group was higher than that in the control group: (30.21 ± 4.05) μg/L vs. (24.19 ± 3.47) μg/L, the difference was statistically significant ( P<0.05). The levels of serum sFas and sFasL in two groups after treatment were lower than those before treatment, and the levels of serum sFas and sFasL in the observation group were lower than those the control group after treatment: (81.57 ± 16.23) ng/L vs. (118.49 ± 25.09) ng/L, (135.47 ± 24.41) ng/L vs. (200.71 ± 30.29) ng/L, the differences were statistically significant ( P<0.05). After treated for 1 month, the CSS scores in the observation group was lower than the control group: (13.48 ± 2.15) scores vs. (17.22 ± 3.02) scores; the WMS, MMSE, and ADL scores in the observation group were higher than those in the control group: (97.75 ± 10.27) scores vs. (88.43 ± 9.16) scores, (23.82 ± 2.50) scores vs. (21.38 ± 2.19) scores, (60.16 ± 6.24) scores vs. (51.29 ± 5.52) scores, the differences were statistically significant ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Electromyography biofeedback therapy combined with oxiracetam has a significant effect in the treatment of elderly patients with VaD. It can significantly improve vascular endothelial function, regulate apoptosis factors, strengthen cognitive function, promote recovery of nerve function and daily living ability without increasing adverse reactions.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

Objective:To explore the value of synthetic MRI in quantitative monitoring of knee joint structural and cartilage changes of amateur marathon runners before and after the whole marathon.Methods:Totally 26 amateur marathon enthusiasts from Zhuhai City, Guangdong Province were recruited from October 2019 to January 2020. The right knee joints were scanned 1 week before the race and within 48 h after the race. The scanning sequence included the three-dimensional proton density weighted image with isotropic (3D-CUBE-PD) sequence and synthetic MRI sequence. The conventional contrast weighted images T 1WI, T 2WI, proton density (PD) weighted imaging, short-T 1 inversion recovery (STIR) and T 1, T 2, PD mapping were obtained by the latter scans. The 3D-CUBE-PD sequence was used as a reference to evaluate the detection of knee joint lesions. The knee articular cartilage was divided into 8 subregions: central medial femoral condyle (CMFC), posterior medial femoral condyle (PMFC), central lateral femoral condyle (CLFC), posterior lateral femoral condyle (PLFC), medial tibia plateau (MTP), lateral tibia plateau (LTP), patella and trochlear. Based on the synthetic MRI quantitative mapping, the T 1, T 2 and PD values of each cartilage subregion were measured independently by 2 radiologists. The ICC was used to evaluate the consistency of the measurement between observers. The T 1, T 2 and PD values of knee cartilage before and after marathon exercise were compared by Wilcoxon signed rank test. Results:The 2 radiologists had good consistency in the measurement of T 1, T 2 and PD values of knee articular cartilage with the ICC values of 0.912, 0.933 and 0.954, respectively. The synthetic MRI quantitative mapping sequence can detect all cartilage damage ( n=3) and joint effusion ( n=15), and 7 of 9 meniscus injuries were detected. The T 1, T 2 and PD values of the knee cartilage as a whole before the race were higher than those after race, and the differences were statistically significant (all P<0.05). The T 1 values were statistically significant except patellar cartilage and trochlear cartilage, and T 2 values were significantly different in the CMFC, LTP, MTP ( P<0.05). Conclusion:Synthetic MRI has a good display of knee joint structural lesions, and its quantitative parameters T 1, T 2 and PD can detect the changes of knee cartilage before and after marathon.

Objective To express and purify two domains GcⅠand GcⅡof Xinjiang hemorrhagic fever virus (XHFV) glycoprotein, and to study its immunogenicity and the effects on immune response in mice. Methods The prokaryotic expression plasmids of pET28a-GcⅠand pET32a-GcⅡwere constructed and transformed into E. coli BL21, respectively. The expression and purification conditions of rGcⅠand rGcⅡproteins were optimized. The antigenicity of the fusion protein was detected by Western Blot and enzyme-linked immunosorbent assay (ELISA). BALB/c mice were immunized by protein immunization and DNA priming-protein boosting. The mice were randomly divided into 5 groups, including pVAX1-GcⅠ+rGcⅠgroup, pVAX1-GcⅡ+rGcⅡgroup, rGcⅠgroup, rGcⅡgroup and saline group (control group) with 7 mice in each group. The serum antibody titer of mice was detected by indirect ELISA, and the immune effect was evaluated by spleen T lymphocyte proliferation assay and cytokine content determination. Results The fusion proteins rGcⅠand rGcⅡwere purified and obtained, which could react with positive serum of sheep and had good antigenicity. After three immunizations, the IgG levels in the serum of each experimental group were significantly higher than those in the control group (all P<0.001). The serum antibody titers of the experimental groups were reached above 1:12800. Among them, the concentration of Th2 type cytokine interleukin-4 (IL-4) in the spleen cell culture supernatant of rGcⅡ[(79.97±7.47) ng/L] and pVAX1-GcⅡ+rGcⅡgroup [(61.43±9.27) ng/L] was significantly higher than (24.29±3.81) ng/L of the control group, respectively (all P<0.01). The highest mass concentration [(42.46 ±2.60) ng/L] of Th1 type cytokine interferon-γ(IFN-γ) was observed in the pVAX1-GcⅡ+rGcⅡ group, which was significantly higher than (20.33±1.67) ng/L of the control group, and the difference was statistically significant (P<0.001). That showed a significant antigen-specific splenic T lymphocyte proliferation (P<0.001). Conclusions The purified recombinant proteins rGcⅠand rGcⅡhave good immunogenicity, which can make the immune system T lymphocytes tend to Th2 response, and pVAX1-GcⅡ combined with recombinant protein GcⅡ can induce better antigen-specific immune effect. And pVAX1-GcⅡ combined with recombinant protein GcⅡis expected to be used as vaccine candidates for the prevention and control of XHFV.

Objective To explore and compare the clinical efficacy of levetiracetam tablets and compound sodium valproate sustained release tablets in the treatment of children and adolescents with epilepsy.Methods From April 2017 to April 2018,80 children and adolescents with epilepsy treated in Chaonan Minsheng Hospital of Shantou were selected as study objects,and they were randomly divided into two groups by drawing lots,with 40 cases in each group.The observation group was given levetiracetam tablets,and the control group was treated with valproate.The improvement of EEG after therapy,the total effective rate,and the incidence of adverse reactions were observed and evaluated.Results The EEG improvement rates after treatment for 6 months in the observation group and control group were 41.17％,45.71％,respectively,the difference was not statistically significant(x2 =0.508,P ＞0.05).The EEG improvement rates after treatment for 9 months in the observation group and control group were 70.58％,74.28％,respectively,the difference was not statistically significant (x2 =0.225,P ＞ 0.05).The total effective rate in the observation group was 92.50％,which was 95.00％ in the control group,the difference was not statistically significant between the two groups (x2 =0.354,P ＞ 0.05).However,the incidence rate of adverse reactions of the observation group(22.50％) was significantly lower than that of the control group(45.00％)(x2 =6.864,P ＜ 0.05).Conclusion Both levetiracetam tablets and compound sodium valproate sustained release tablets have appreciable efficacy and safety in the treatment of epilepsy in children and adolescents,but levetiracetam therapy has less adverse reactions,which deserves further promotion in monotherapy of epilepsy in children and adolescents.

Objective To construct a human renal epithelial cell line HEK293T by CRISPR-Cas9-based site-directed knock-in of vascular endothelial growth factor 165 (VEGF165) gene, and avoid the off-target effect caused by lentivirus infection. Methods The VEGF165 expression vector with homologous arm (pUCm-T-VEGF165 plasmid) and the sgRNA expression vector [pSpCas9(BB)-2A-Puro-sgRNA plasmid] were designed and constructed based on the DNA sequence of the EZH2 gene, and then co-transfected into HEK293T cells. The expression of VEGF165 mRNA was detected by qPCR and the expressions of VEGF165 proteins were detected by Western Blot. Results The qPCR and Western Blot results showed that, comparing with the control, the pUCm-T-VEGF165 plasmid and pSpCas9(BB)-2A-Puro-sgRNA plasmid, the expression of the co-transfection plasmid were significantly increased, i.e. 3.42±0.30 vs. 1.02±0.21, 1.13±0.16 and 0.98±0.18 for the VEGF165 mRNA level (all P<0.01), and 1.13±0.16 vs. 1.02±0.06, 0.88±0.03 and 0.80±0.05 for the VEGF165 protein level (all P<0.01), respectively. Besides, the expression of EZH2 was significantly down-regulated, i.e. 0.14±0.06 vs. 1.08±0.11, 1.02±0.12 and 1.13±0.16 for the EZH2 mRNA level (all P<0.01), and 0.23±0.03 vs. 1.05±0.13, 0.91±0.04 and 0.81±0.06 for the EZH2 protein level (all P<0.01), respectively. This result showed that the VEGF165 was successfully inserted into the EZH2 genome, interfering the EZH2 expression. Conclusions VEGF165 gene can be successfully knocked into HEK293T cells by CRISPR/Cas9 system.

Objective To explore the factors, characteristics and imaging manifestations of ankle joint injury in amateur marathoners (no formal training and no marathon career). Methods From December 2018 to March 2019, the amateur marathon runners in Guangdong Zhuhai had been recruited as research subjects according to the study inclusion and exclusion criteria. The questionnaires were used to collect relevant data, and the subjects underwent MRI scans of the ankle joint. The ankle joint special phased array coils were used to perform fast spin echo sequence (TSE) coronal T1WI and proton density?weighted fat?suppression sequence (PDWI?FS). Axial, coronal and sagittal scans, three?dimensional?double echo steady?state sequence (3D?DESS) and three?dimensional variable flip angle fast spin echo sequence (3D?SPACE) scans were also acquired. The results of the examination were independently analyzed by two radiologists (5 and 17 years of work experience, respectively) on the ligament, tendon, bone marrow and ankle joint injuries. When they had inconsistent views, the diagnosis provided by the third radiologist (27 years of work experience) was considered a final diagnosis. The relationship between ankle injury and different running postures, the number of participating in marathons and training intensity was analyzed, and the independent sample χ2 was used for statistical analysis. The consistency of two radiologists was tested by Kappa test. Results According to the inclusion and exclusion criteria, 39 subjects were included, with 64 ankles totally, 35 right ankles and 29 left ankles. MRI showed that (1) Ligament injuries: 28 ankles were anterior talofibular ligament injuriy;50 ankles were posterior talofibular ligament injury; 60 ankles the calcaneofibular ligament injuries and 54 ankles were deltoid ligament injuries, without complete injury. (2) Tendon sheath effusion and injuries: peritendinous effusion was common, with 47 flexor hallucis longus tenosynovitis, 49 posterior tibialis tenosynovitis, 37 flexor digitorum longus tenosynovitis, 7 peroneus longus tenosynovitis and 5 peroneus brevis tenosynovitis. (3) Synovitis effusion: 43 posterior ankle synovitis and local effusion. (4) Others: cartilage injury in 2 ankles, bone marrow edema in 8 ankles, and among them stress fracture in 2 ankles. The two radiologists had good consistency with the Kappa value of 0.91. Regarding the running posture, the incidence of ligaments injuries was obviously higher in those who landed on the hind foot than in those landed on front and middle foot,and the difference was statistically significant(P=0.013, χ2 value was 6.191).The incidence of tendon injuries was higher in those who landed on the front middle foot than in those landed on the hind foot, and the difference was statistically significant (P=0.029, χ2 value was 4.775). Those with larger training (training running ≥300 km/month) had significant ankle injury (P=0.005, χ2 value was 7.844). Conclusion The MRI features of ankle joint injuries in amateur marathon volunteers are related to different running postures and training intensity.