Autophagy is a catabolic process responsible for the degradation and recycling of misfolded proteins and damaged organelles for cellular homeostasis. This degradative pathway,closely related to many diseases including cancer,has become a focus of cancer research. lt can serve as a tumor suppressor,also functions as a protective cell-survival mechanism against chemotherapies. Of the autophagy-related proteins,vacuolar protein sorting 34(VPS34)has attracted major attention over the past decade because of its role in autophagic procedure. Recently,three specific inhibitors of VPS34,PlK-Ⅲ,VPSlN1 and SlR405,have been invented,showing unique implications for autophagy reduction and therapeutic benefit in tumor treatment. This paper summarizes the different roles of autophagy in clinical settings and the functional regulation of VPS34 upon post-translational modification and also discusses the application prospects of inhibitors targeting VPS34 or autophagy in cancer prevention and treatment.

Objective To investigate the effects of acetylated HMGB1 on cognitive function in rats with sepsis associated encephalopathy (SAE) and the effect of HMGB1 inhibitor.Methods Forty-eight males mice were randomly assigned to three groups (n=16): sham group (group S),cecal ligation puncture group (group C),cecal ligation puncture+sodium butyrate group (group B).Cecal ligation puncture was applied to establish the SAE model,and group S received sham operation.Rats in groups S and C were injected with normal saline 5 ml/kg 30 min and 4 h after CLP,respectively.The rats in group B were intraperitoneally injected with sodium butyrate 500 mg/kg 0.5 h and 4 h after CLP,respectively.All animals were performed Morris water maze test on 4th day after operation,and the exploring time of space exploration experiments were assessed on 7th day after CLP surgery.IL-6,BDNF,HMGB1 and acetylated HMGB1 expression in hippocampus of all rats were determined by Western Blot.Results Compared with group S,the latency of rats in group C was longer and the exploring time was shorter (P<0.05).Compared with group C,the latency of rats in group B was shorter and the exploring time was longer (P<0.05).Compared with group S,the expression of IL-6,HMGB1 and acetylated HMGB1 in group C increased (P<0.05) and the level of BDNF decreased (P<0.05).Compared with group C,the expression of IL-6,HMGB1 and acetylated HMGB1 in group B decreased (P<0.05) and the level of BDNF increased (P<0.05).Conclusion HMGB1 inhibitor sodium butyrate can inhibit the expression of acetylated HMGB1 in the hippocampus of SAE rats,and reduce the cognitive impairment induced by sepsis.

Objective To investigate the role of hippocampal cyclophilin D (CypD) in sepsis-associated encephalopathy in rats.Methods A total of 36 adult male Sprague-Dawley rats,aged 3-4 months,weighing 300-400 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis + CypD inhibitor cyclosporin A group (CsA group).Sepsis was induced by cecal ligation and puncture (CLP).Cyclosporin A 6 mg/kg was injected intraperitoneally at 30 min before CLP in group CsA.All the animals underwent Morris water maze test on 4th day after CLP.The animals were sacrificed after the test,and the hippocampus was isolated for determination of the expression of cytochrome c (Cyt c),CypD,caspase-3,brain-derived neurotrophic factor (BDNF),phosphorylated protein kinase A (p-PKA),and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB).Results Compared with group Sham,the escape latency was significantly prolonged,the space exploration time was shortened,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was up-regulated,and the expression of BDNF was down-regulated in S and CsA groups (P＜0.05).Compared with group S,the escape latency was significantly shortened,the space exploration time was prolonged,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was down-regulated,and the expression of BDNF was up-regulated in group CsA (P＜0.05).Conclusion Hippocampal CypD may be involved in the pathophysiological mechanism of sepsis-associated encephalopathy,and the downstream mechanism is probably related to promotion of activation of PKA/CREB signaling pathway in rats.

Objective To evaluate the effect of exogeneous adiponectin on hippocampal advanced glycation end products (AGEs)-reactive oxygen species (ROS)-endoplasmic reticulum stress (ERS) pathway in aged mice with postoperative cognitive dysfunction (POCD).Methods Thirty-two healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were randomly divided into 4 groups (n=8 each) using a random number table: control group (group C), POCD group, exogeneous adiponectin group (group APN), and vehicle group (group Veh).Splenectomy was performed to establish the POCD model in aged mice anesthetized with intraperitoneal pentobarbital sodium.In group APN, adiponectin 0.1 μg/g (in 2 μl of phosphate buffer solution) was injected into the lateral cerebral ventricle at 30 min before establishing the model.Phosphate buffer solution 2 μl was given at 30 min before establishing the model in group Veh.Cognitive function was assessed on day 7 after surgery.The mice were then sacrificed, and the hippocampus was harvested for determination of the area of AGE deposition (by immunohistochemistry), levels of ROS (by flow cytometry), and levels of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), caspase-12 and ROS (using Western blot).Results Compared with group S, the freezing time in the contextual fear conditioning test was significantly shortened, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were increased, and the level of GRP78 was decreased in POCD, APN and Veh groups.Compared with POCD and Veh groups, the freezing time in the contextual fear conditioning test was significantly prolonged, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were decreased, and the level of GRP78 was increased in group APN.Conclusion Exogeneous adiponectin decreases the occurrence of POCD probably by blocking hippocampal AGEs-ROS-ERS pathway in aged mice.

BACKGROUND:Perioperative high hidden blood loss affects the recovery of joint function after total hip replacement. OBJECTIVE:To analyze the reliability of the Mini Nutritional Assessment on evaluating the nutritional status in elderly patients with femoral neck fracture on admission, and to investigate the effect of nutritional status variation on hidden blood loss after total hip replacement. METHODS:234 elderly patients with femoral neck fracture underwent total hip replacement. By using Mini Nutritional Assessment, patients were randomly divided into three groups:wel-nourishment group (n=52), malnourishment at risk group (n=92), and malnourishment group (n=90). The results were used to analyze the correlation of Mini Nutritional Assessment and serological nutrition indicators, and to hidden blood loss. RESULTS AND CONCLUSION:(1) Hidden blood loss:101 patients suffered from high hidden blood loss. Hidden blood loss, its proportion to total blood loss and incidence of high hidden blood loss gradual y increased with the deterioration of the nutritional status (P<0.05). (2) Mini Nutritional Assessment:Pre-operative Mini Nutritional Assessment score, and the incidence of hidden blood loss evaluated by albumin, prealbumin, transferrin, lymphocyte count, the percentage of lymphocytes and hemoglobin was significantly higher in patients with high hidden blood loss than those with low hidden blood loss (P<0.01). (3) Results of correlation analysis:High hidden blood loss was positively correlated with pre-operative Mini Nutritional Assessment, albumin, prealbumin, transferrin, the percentage of lymphocytes and hemoglobin (P<0.05). (4) These findings confirm that risk evaluation with Mini Nutritional Assessment is a reliable method to assess the nutritional status in elderly patients undergoing total hip replacement. Its combination with various serum nutrition indicators can determine high hidden blood loss and the prognosis.

Objective To retrospectively analyze the antimicrobial resistance phenotype and molecular typing characteristics of Salmonella (S.) typhi and S. paratyphi in Jiangsu province from 2012 to 2015. Methods The samples were collected from typhoid and paratyphoid patients in Jiangsu province. The biochemical identification and serotyping were carried out after isolation and culture. Kirby-Bauer (K-B) testing was used to detect the drug susceptibility of the strains. The molecular typing characteristics of S. typhi and S. paratyphi were analyzed by pulsed field gel electrophoresis (PFGE). Results The resistant rates of 134 S. typhi and S. paratyphi A strains to nalidixic acid were highest (61.2%and 86.7%), while the resistant rates to remaining antibiotics were less than 15.0%. Most of S. typhi and S. paratyphi A strains were resistant to only one antibiotic. Multidrug-resistant (MDR) strains of S. typhi and S. paratyphi A accounted for 2.6% and 13.3%respectively. The composition of the all-sensitive strains of S. typhi increased by 44.3%in 2015, at the same time, there were also MDR S. pa ra typhi A strains, which were resistant to 5 and 6 antibiotics. S. paratyphi A could be divided into eight molecular patterns by PFGE, showing that the similarity between the MDR strains and other strains was relatively low. The S. paratyphi A strains with same pattern were resistant to same antibiotics. S. typhi could be divided into 68 molecular patterns by PFGE, with large variability between different patterns. There was no corresponding relationship between the patterns and the drug resistance characteristics. Conclusions The overall antibiotic resistance of S. typhi and S. paratyphi A strains showed a decreasing trend, but the number ofantibiotics to which they were resistant increased. PFGE patterns of S. typhi showed diversity without correspondence to antibiotic characteristics. PFGE patterns of S. paratyphi A were less with correspondence to antibiotic characteristics. We should pay more attention to key patterns in key areas.

BACKGROUND:Stage Ⅲ Kümmell's disease is characterized by a high degree of vertebral compression and posterior wall defects.Most of the patients are elderly people with severe osteoporosis and various medical diseases.Clinically,some surgical methods are often at high risk and are controversial. OBJECTIVE:To investigate the clinical efficacy of screw placement combined with transpedicular impaction bone grafting in the treatment of stage Ⅲ Kümmell's disease. METHODS:The clinical data of injured vertebral screw placement combined with transpedicular impaction bone grafting in treatment of stage Ⅲ Kummell's disease from May 2016 to August 2021 were retrospectively analyzed.Visual analog scale score,Oswestry disability index,anterior vertebral heights,kyphotic Cobb angle and American Spinal Injury Association(ASIA)impairment scale were used to evaluate the effects of surgery.The operation time,intraoperative blood loss and complications were recorded.CT scans were used to evaluate the healing of injured vertebrae at the final follow-up visit. RESULTS AND CONCLUSION:(1)A total of 26 patients were included,with 7 males and 19 females,at the age range of 62-81 years[mean(69.7±4.8)years].The follow-up time was 18-60 months[mean(35.1±8.9)months].The average operative duration was 133.5 minutes(100-165 minutes),and the average intraoperative blood loss was 285.3 mL(210-350 mL).(2)Visual analog scale and Oswestry disability index scores 1 week after surgery were significantly lower than those before surgery.(3)At 1 week after surgery,the anterior vertebral height corrections and the Cobb angle were(9.0±0.7)mm and(16.2±1.0)°,respectively.During the follow-up period,the loss of vertebral height and kyphosis correction were(5.1±0.3)mm and(8.0±0.4)°,respectively.(4)14 patients(54%)had ASIA grade D before operation,which recovered to grade E at the last follow-up.CT scan showed that all patients achieved good osseous union.(5)Complications occurred in seven patients(27%),including hypostatic pneumonia in two cases,postoperative superficial wound tissue liquefaction in two cases,and adjacent vertebral compression fractures in three cases.(6)It is concluded that screw placement of the injured vertebra combined with transpedicular impaction bone grafting can rapidly rebuild spinal stability,effectively relieve pain and improve neurological function in the treatment of stage Ⅲ Kümmell's disease.This technique is an effective and relatively minimally invasive surgical option.

Objective: To investigate the effect of a Passy-Muir speaking valve (PMV) on the biomechanics of swallowing and on aspiration among persons tracheotomized after brain damage. Methods: Twenty tracheotomized patients with aspiration after brain injury were selected and randomly divided into a non-PMV intervention group and a PMV intervention group, each of 10. Both groups were given routine swallowing training, while the PMV intervention group was additionally provided with a PMV and trained to use it. The treatment ended when the tracheal tube was removed or after 2 weeks. High-resolution manometry and videofluoroscopy were used to evaluate the maximum pressure in the velopharynx (VP-Max), the maximum post-deglutitive upper esophageal sphincter (UES) pressure (UES-Max) and Rosenbek penetration aspiration (PAS) scores for both groups before and after the treatment. Results: Before the treatment there was no significant difference between the two groups in terms of average VP-Max, UES-Max or PAS score. After the treatment, the average VP-Max and UES-Max had increased significantly in both groups, and the average PAS score of the PMV intervention group had decreased significantly. There was a significant positive correlation between the increases in VP-Max and the decrease in PAS scores. Conclusion Inserting a PMV can improve velopharynx contraction and post-deglutitive UES among persons tracheotomized after a brain injury. The increase in maximum velopharynx pressure is positively correlated with decreases in aspiration.