Objective By simulating acute hypoxic conditions, an experimental model of intestinal stress injury in plateau mice was established to explore the pathogenic mechanism of acute gastrointestinal diseases in plateau, and to lay foundation for preventive and therapeutic measures.MethodsThirty-six SPF-grade adult male BALB/c mice were randomly divided into four groups: normoxic 24 h, normoxic 72 h, hypoxic 24 h, and hypoxic 72 h, based on body weight using a randomized numerical table method, with nine mice in each group. Mice in the normoxic group were kept in a conventional barrier environment, while those in the hypoxic group were placed in a hypoxic chamber within the barrier environment with oxygen concentration set at 10% to simulate plateau conditions. They were subjected to stress for 24 h and 72 h, respectively, in order to establish a model of intestinal injury induced by acute hypoxia. After modeling, the mice were weighed, anesthetized with 1% pentobarbital sodium, and then euthanized by cervical dislocation. Duodenal and colonic tissues were collected. Histopathological morphology of intestinal tissues was observed after HE staining. Western blotting and immunohistochemistry were used to detect the expression levels of tight junction-related proteins in intestinal tissues. Real-time fluorescence quantitative PCR was performed to measure the expression levels of inflammatory cytokines and chemokines. TUNEL staining was used to assess apoptotic activity of intestinal epithelial cells, thus evaluating intestinal injury-related phenotypes in this model.Results Compared with the normoxic groups, mice in the 24 h and 72 h hypoxia groups showed weight loss, shortened duodenal villi, abnormal crypt structure, and decreased villus/crypt ratio. The colonic mucosa was infiltrated with inflammatory cells and irregular crypt structure. Expression levels of Occludin and zonula occludens-1 (ZO-1) were significantly decreased in duodenal and colonic tissues of mice in the 24 h and 72 h hypoxia groups (P<0.05). The expression of pro-apoptotic protein Bax was significantly up-regulated while expression of anti-apoptotic protein Bcl-2 was significantly down-regulated in duodenal tissues (P<0.05). Apoptotic activity of intestinal epithelial cells was significantly enhanced (P<0.05). In addition, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) mRNA levels were significantly increased in duodenal tissues after 24 and 72 h of hypoxic stress(P<0.05). After 24 h of hypoxic stress, there was no significant change in the expression levels of inflammatory cytokines in colon tissues (P>0.05), but after 72 h, the expression levels of pro-inflammatory factors IL-1β, TNF-α, IL-6, MCP-1, and anti-inflammatory factor IL-10 mRNAs significantly increased in colon tissues of mice (P<0.05).Conclusion The usage of a hypoxia chamber to simulate an acute hypoxic environment in plateau can lead to abnormal intestinal tissue structure, intestinal barrier dysfunction, and induce intestinal epithelial cell apoptosis, triggering an intestinal inflammatory response in stress mice. These findings indicate the successful construction of a mouse model for an acute hypoxic stress-induced intestinal injury.

Objective Given that psychosocial stress can contribute to a series of diseases,such as inflammatory bowel disease and irritable bowel syndrome,we aimed to establish an experimental chronic restraint mouse intestinal stress injury model as a basis for exploring the pathogenic mechanism of chronic restraint stress-induced gastrointestinal diseases,and for developing preventive and curative measures.Methods Eighteen male SPF-grade BALB/c mice were acclimatized for 7 days and then divided into a control group and a chronic restraint stress group according to body weight,using a randomized numerical table method.The mice were subjected to restraint stress for 3 hours per day for 14 days to establish an intestinal injury model.The model was evaluated by observing body weight,pathological changes in intestinal histomorphology,expression of tight junction proteins,apoptosis of intestinal epithelial cells,and mRNA expression levels of inflammatory cytokines.Results After 14 days of chronic restraint stress,model mice showed weight loss,shortened duodenal villus height,abnormal crypt structure,a decreased villus/crypt ratio,colonic mucosal inflammatory cell infiltration,and irregular crypt structure.Protein immunoblotting,immunohistochemistry,and immunofluorescence staining showed that the expression levels of the duodenal and colonic tight junction proteins Occludin and Claudin-1 were significantly decreased in mice after chronic restraint stress(P＜0.05),while expression levels of the apoptotic protein cleaved-caspase-3 in intestinal epithelial cells were significantly increased(P＜0.05).Regarding the mRNA expression levels of intestinal inflammatory factors and chemokines,chronic restraint stress for 14 days significantly increased the gene expression levels of interleukin(IL)-1β,IL-6,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α,and IL-10 in the duodenum of mice(P＜0.05),and significantly increased the gene expression levels ofIL-1β,IL-6,and MCP-1 in the colon(P＜0.001).Conclusions The use of a behavioral restriction device to restrain mice continuously for 14 days led to abnormal intestinal tissue structure,intestinal barrier dysfunction,and intestinal epithelial cell apoptosis,and triggered an intestinal inflammatory response in the stressed mice,indicating successful establishment of a mouse model of intestinal injury by chronic restraint stress.

The intestine is the largest immune and metabolic site in the body and is thus important for animal health.The integrity of the mucosal barrier and function are fundamental factors protecting the health of the intestine.Stress has been reported to have profound effects on the gastrointestinal tract,including altering gut permeability,the intestinal barrier,and homeostasis.Tryptophan is a functional essential amino acid that alters the gut microbiota and regulates intestine structural and functional change,thus contributing to host physiology and metabolism.Changes in tryptophan metabolism and its metabolites in brain and intestinal tissues during stress suggest that tryptophan may play an important role in the stress response.We therefore review the literature on the mechanisms underlying stress-related diseases and the role of tryptophan metabolism in the regulation of gut homeostasis,with particular focus on functional bowel disorders and their relationship to stress,to provide a theoretical foundation for targeting tryptophan in stress-related intestine diseases.

Although geriatric diseases are complicated due to the coexistence of many diseases,they often have a common pathological basis and are closely related to the pathogenesis of deficiency and excess in traditional Chinese medicine.Exploring the characteristics of the pathogenesis of deficiency and excess diseases in the elderly is helpful to keep simplicity and restrain complexity,grasp the law of occurrence and development of diseases in the elderly as a whole,and give full play to the advantages of traditional Chinese medicine in the prevention and treatment of chronic diseases.Based on the fundamental characteristics of deficiency and excess in senile diseases,researcher Hu Jingqing further summarized that"essence deficiency,Yin deficiency,Yang deficiency,qi deficiency,blood deficiency"and"qi stagnation,phlegm dampness,blood stasis,fire and heat,and latent wind"are the most common pathogenesis in the occurrence and development of senile diseases.Among them,deficiency is the basic pathogenesis of senile diseases,especially deficiency of kidney essence.Excess disease is the key pathogenesis of the development and changes of senile diseases.Qi stagnation is often the initial step in the development of senile diseases.Phlegm dampness and blood stasis are the pathological products of"excess due to deficiency"and are also the main secondary pathogenesis of senile diseases.In clinical identification of senile diseases,attention should be paid to grasping the pathogenesis of deficiency and excess and its concurrent changes.

To solve the problems in the course teaching of Pharmacokinetics and change the current situation of the course, a pharmacokinetic solution program based on Excel has been developed. The program, based on Excel, is the most widely used data processing software. The data processing and drawing functions of Excel are used and encapsulated as a program by Excel-VBA. The program is specially used in pharmacokinetic teaching, which includes 25 solution templates arranged according to the 5th edition of Biopharmaceutics and Pharmacokinetics, a textbook published by the People's Medical Publishing House Co., LTD. Each solution template includes six functional areas: operation setting area, data input area, data relationship display area, return parameter output area, pharmacokinetic parameter output area and chart area. In this course, the teaching content is reorganized. Starting from a case, the concept and knowledge of pharmacokinetics are taught by explaining how to apply the program to solve case problems. After years of practice, the teaching effect has been significantly improved.

To investigate the in situ intestinal absorption characteristics and pharmacokinetic behavior of metformin-resveratrol compound water-in-oil nanoemulsion (MRCE) in rats, the in situ intestinal perfusion model was constructed in rats to study the intestinal absorption characteristics of MRCE in different intestinal segments. Male Sprague-Dawley rats were randomly divided into two groups. After intragastric administration of metformin and MRCE, blood was taken at a preset time point. The content of metformin in intestinal perfusion samples and blood samples at various time points was determined by HPLC. Plasma concentration-time profiles of free metformin and MRCE were calculated, and the main pharmacokinetic data were processed and analyzed by DAS 2.1.1 software. The absorption rate constant (Ka), the effective permeability (Peff) and the percentage of absorption (PA) of MRCE in each intestinal segment were significantly higher than those of metformin (P < 0.05). The area under the drug-time curve (AUC0-72 h), the half-life (t1/2) and mean residence time (MRT0-72 h) of MRCE were 1.68, 11.25 and 6.97 times of metformin, respectively (P < 0.01).The relative bioavailability of MRCE was 167.6%. The 90% confidence interval of AUC0-72 h was 156.9%-187.4%, which was not within the standard interval of bioequivalence. The intestinal absorption of MRCE was significantly better than that of free metformin; MRCE improved the oral bioavailability of metformin and was not bioequivalent to metformin.

The stability and pharmacokinetic properties of hyaluronic acid-modified asparaginase (Asp) self-assembled bionic nanocapsules (ASNCs) were preliminarily investigated. ASNCs were prepared by molecular self-assembly method to investigate their morphology, particle size, zeta potential and antitrypsin stability. After intravenous injection of free Asp and ASNCs, rat plasma samples at different times were taken to determine Asp activity. Pharmacokinetic parameters were calculated by DAS pharmacokinetic software. The particle size of ASNCs was (99.17 ± 0.21) nm and the potential was -(13.13 ± 0.60) mV. In trypsin solution, ASNCs showed more excellent stability. The area under the activity-time curve (AUC0-48 h) of ASNCs was about 2 times higher than that of Asp; the mean residence time (MRT0-48 h) was about 1.7 times higher than that of Asp, and the bioavailability was 195% of Asp. The results showed that ASNCs could improve the stability and bioavailability of Asp against trypsin and prolong the circulation time of Asp in vivo.

The aim of this study was to investigate the in vivo pharmacokinetic behavior characteristics and in situ intestinal absorption characteristics of the evodiamine lipidic nanoparticle in rats. Evodiamine lipidic nanoparticle was prepared by the solvent evaporation methods. The particle size and zeta potential of evodiamine lipidic nanoparticle were measured by dynamic light scattering analysis. Male SD rats were divided into two groups randomly. Each group was given single dose of evodiamine and evodiamine lipidic nanoparticle by gavage at evodiamine dose of 250 mg/kg,respectively. The blood samples were collected at scheduled time points. The content of evodiamine in plasma samples was determined by high performance liquid chromatography (HPLC) method. The main pharmacokinetic parameters of evodiamine and evodiamine lipidic nanoparticle were calculated using DAS 2.1.1 software. Moreover,the single-pass intestinal perfusion model was also established in rats to investigate the in situ intestinal absorption characteristics of evodiamine lipidic nanoparticle. The mean particle size and mean zeta potential of evodiamine lipidic nanoparticle were 180.10 nm and -17.90 mV,respectively. The area under the curve of evodiamine and evodiamine lipidic nanoparticle were (862.60±14.03) and (4084.31±17.21) μg/L·h,respectively,and the peak concentration were (163.40±13.27) and (616.90±21.04) μg/L,respectively. Moreover,the absorption of evodiamine lipidic nanoparticle was significantly higher than that of evodiamine in each segment of intestinal tract in rats (P<0.05). The absorption of evodiamine lipidic nanoparticle in colon was better than those of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum and ileum. The absorption rate constant of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum,ileum and colon were (45.10±6.08)×10-5,(48.20±1.21)×10-5,(22.10±3.18)×10-5,(59.10±1.21)×10-5 and (90.00±3.85)×10-5 s-1,respectively,and the effective permeability coefficient in duodenum,jejunum,ileum and colon was (44.10±0.51)×10-5,(17.21±0.77)×10-5,(35.36±0.31)×10-5 and (40.33±0.34)×10-5 cm/s,respectively.All in all, evodiamine lipidic nanoparticle remarkably improved the in situ intestinal absorption of evodiamine in different segments of the intestinal tract in rats and its oral bioavailability in rats.

Objective:To explore the significance of multimodal monitoring in the monitoring and treatment of neurocritical care patients.Methods:104 neurocritical care patients admitted to the department of Critical Care Medicine of Fujian Provincial Hospital from March 2019 to January 2020 were enrolled. Patients were randomly assigned into two groups, with 52 in each group. In the routine monitoring treatment group, heart rate, blood pressure, respiratory rate and the changes in consciousness and pupils were monitored after operation. The patients were treated with routine medicine to reduce intracranial pressure (ICP), maintain proper cerebral perfusion pressure (CPP), balance fluid intake and output, and maintain the airway clear. Patients in the multimodal monitoring treatment group were treated with invasive ICP monitoring, ultrasound to assess brain structure, ultrasound to measure optic nerve sheath diameter (ONSD), transcranial color doppler (TCCD), internal jugular venous blood oxygen saturation monitoring, near-infrared spectroscopy (NIRS), non-invasive cerebral blood oxygen saturation monitoring and quantitative electroencephalogram monitoring. According to the monitoring results, the patients were given targeted treatment with the goal of controlling ICP and improving brain metabolism. The length of intensive care unit (ICU) stay, the incidences of neurological complications (secondary cerebral infarction, cerebral hemorrhage, high intracranial pressure, etc.), and the incidences of poor prognosis [6 months after the onset of Glasgow outcome score (GOS) 1 to 3] were compared between the two groups. Spearman rank correlation analysis of the correlation between invasive ICP and the ICP value which was calculated by TCCD. The receiver operating characteristic (ROC) curve of invasive ICP and pulsatility index of middle cerebral artery (PI MCA) were used to predict poor prognosis. Results:The length of ICU stay in the multimodal monitoring treatment group was significantly shorter than that of the routine monitoring treatment group (days: 6.27±3.81 vs. 9.61±5.09, P < 0.01), and the incidence of neurological complications was significantly lower than that in the routine monitoring treatment group (9.62% vs. 25.00%, P < 0.05). In the multimodal monitoring treatment group, 37 cases had a good prognosis and 15 cases had a poor prognosis, while the routine monitoring treatment group had a good prognosis in 27 cases and a poor prognosis in 25 cases. The incidence of poor prognosis in the multimodal monitoring treatment group was lower than that of the routine monitoring treatment group (28.85% vs. 48.08%, P < 0.05). In the multimodal monitoring treatment group, the invasive ICP and PI MCA of patients with good prognosis were significantly lower than those of patients with poor prognosis [invasive ICP (mmHg, 1 mmHg = 0.133 kPa): 16 (12, 17) vs. 22 (20, 24), PI MCA: 0.90±0.33 vs. 1.39±0.58, both P < 0.01]. There was no significant difference in resistance index of the middle cerebral artery (RI MCA) between the good prognosis group and the poor prognosis group (0.63±0.12 vs. 0.66±0.15, P > 0.05). There was a positive correlation between the invasive ICP and the ICP value which was calculated by TCCD ( r = 0.767, P < 0.001). ROC curve analysis showed that the area under ROC curve (AUC) of invasive ICP for poor prognosis prediction was 0.906, the best cut-off value was ≥ 18 mmHg, the sensitivity was 86.49%, and the specificity was 86.67%. The AUC of PI MCA for poor prognosis prediction was 0.759, the best cut-off value was ≥ 1.12, the sensitivity was 81.08%, and the specificity was 60.00%. The AUC of invasive ICP was greater than PI MCA ( Z = 2.279, P = 0.023). Conclusion:Comprehensive analysis of multimodal monitoring indicators for neurocritical care patients to guide clinical treatment can reduce the length of hospital stay, and reduce the risk of neurosurgery complications and disability; invasive ICP can predict poor prognosis of neurocritical care patients.

Objective To evaluate the use of intercostal trocars (ICS) and transthoracic trocars in laparoscopic resection of liver segments 7 and 8.Method From November 2015 to June 2017,20 patients who underwent laparoscopic S7 or 8 segmentectomy for liver tumors in the Department of Hepatobiliary Surgery,the First Affiliated Hospital,Guangxi Medical University were analyzed retrospectively.Results Ports were inserted at the 8th or 9th ICS,respectively,in addition to the conventional abdominal ports.The mean operation time was 225.0 min (110.0 ～ 486.0 min).Anatomical resection was completed in 1 patient,and non-anatomical resection in 19 patients.The conversion rate was 0％.Pringle's maneuver was used in 9 patients.The mean blood loss was 85.0 (25.0 ～410.0) ml,and the mean length of hospital stay was 7.0 (5.0 ～ 12.0) days.The complication rate was 10.0％.Pathologic findings revealed that 17,2,1 patient(s) had HCC,hemangioma,and inflammatory nodule,respectively.The mean tumor size and tumor free margin were 33.8 (15.0 ～ 74.0) mm;and 15.0 (1.0 ～ 30.0) mm,respectively.There was no HCC recurrence on follow-up,expect for one patient who developed tumor recurrence at 20 months after laparoscopic liver resection.Conclusions In selected patients,laparoscopic liver resection using intercostal trocars was useful and safe for tumors located in liver segments 7 and 8.The long-term oncologic outcomes need to be further evaluated.