New advances in stroke and cerebral embolism protection devices in transcatheter aortic valve replacement / 中国介入心脏病学杂志

Stroke is one of the most serious complications of transcatheter aortic valve replacement(TAVR),tremendously increasing mortality and the loss of neurocognitive function.Since TAVR is expected to further spread into lower-risk patient groups,there will be greater emphasis to obviate such serious complications.One possible technique for preventing stroke is using cerebral embolic protection devices(CEPDs).CEPDs are designed for capturing or deflecting emboli that are enter route to the brain and hence to protect the brain from embolism.Since this is a rapidly growing field with recent advances,and the impact of CEPD on preventing neurological events is still limited,there is an urgent need for understanding the role of CEPD in preventing clinically significant strokes.Although their clinical utilization is increasing,the risk factors for stroke related to TAVR and evidence for using CEPDs are not yet clear.In this review,we present an overview of the available literature on TAVR related stroke and CEPD,and outline recent advances within this field.

Effect of Huanglian Wendantang on Classical Pathway of Skeletal Muscle Pyroptosis in IGT Rats / 中国实验方剂学杂志

Objective:To explore the effects of Huanglian Wendantang （HLWDT） on pyroptosis of skeletal muscle in rats with impaired glucose tolerance （IGT） and to explain the mechanism based on NOD-like receptor protein 3 （NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD）/interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）/IL-18 signaling pathway. Method:The SD male rats were fed with 45% high-fat diet for 20 weeks to induce the IGT model. After modeling， the rats were randomly divided into a blank group， a model group， a positive control group （metformin hydrochloride， 0.05 g·kg^-1d^-1）， and an HLWDT （7.8 g·kg^-1d^-1） group based on the body weight of rats. The blank group and the model group were fed with the same volume of distilled water. The dose for each group was set as 10 mL·kg^-1d^-1. After four weeks of continuous gavage， blood was collected and serum was separated. The skeletal muscles of rats were stored in liquid nitrogen. Subsequently， serum IL-1<italic>β</italic> and IL-18 were detected by the enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of NLRP3， Caspase-1， and GSDMD were detected by real-time quantitative PCR （Real-time PCR） and Western blot， respectively. The expression of GSDMD， IL-1<italic>β</italic>， and IL-18 proteins in skeletal muscle tissues was detected by immunofluorescence. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of skeletal muscles. Result:Compared with the blank group， the model group showed increased IL-1<italic>β</italic> and IL-18 in serum， and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. Immunofluorescence assay showed that GSDMD， IL-18， and IL-1<italic>β </italic>protein expression in skeletal muscle tissues of the model group was significantly elevated （<italic>P</italic><0.01）. HE staining showed obvious pathological changes in skeletal muscles. Compared with the model group， the HLWDT group and the positive control group could decrease IL-1<italic>β</italic> and IL-18 in serum and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. In addition， immunofluorescence assay revealed that HLWDT could reduce protein expression levels of GSDMD， IL-1<italic>β</italic>， and IL-18 in skeletal muscles of IGT rats （<italic>P</italic><0.01）. The results of HE staining showed that HLWDT could improve the pathological changes of skeletal muscles in IGT rats<bold>.</bold> Conclusion:HLWDT can inhibit skeletal muscle pyroptosis of IGT rats， and the mechanism may be closely related to NLRP3/Caspase-1/GSDMD/IL-18/IL-1<italic>β</italic> signaling pathway.

Comprehensive correction of maxillofacial bone deformity-consideration and combined application of orthognathic surgery and facial contouring surgery / 华西口腔医学杂志

The maxillofacial skeleton is the basis of the contour of the face. Orthognathic surgery and facial contouring surgery change jaw tissue and affect facial appearance in different manners. Orthognathic surgery is the main method to correct dental and maxillofacial deformities. It changes the shape of the jaw and improves the occlusal relationship by changing the three-dimensional position of the jaw. Facial contouring surgery mainly adopts the method of "bone reduction", which changes the "amount"of the jawbone by cutting a part of the bone tissue to improve the facial appearance, generally without changing oral function. The combined use of orthognathic surgery and facial contouring surgery is becoming increasingly common in clinical practice. This also requires oral and maxillofacial surgeons to have a holistic consideration of the comprehensive correction of maxillofacial bone deformity, and to perform comprehensive analysis of jaw deformities and jaw plastic surgery to achieve the most ideal results. The author's team has been engaged in the clinical work of orthognathic surgery and facial contouring surgery and accumulated rich clinical experience in the comprehensive correction of maxillofacial bone deformity. In this article, the indications, treatment goals, treatment modes, treatment methods, and key points in the surgical operations of comprehensive maxillofacial bone surgery were summarized.

Mechanism of Huanglian Wendan Decoction in improving impaired glucose tolerance based on skeletal muscle NLRP3/caspase-1/IL-1β, IL-18 pathway / 中国中药杂志

This study investigated the mechanism of improving impaired glucose tolerance(IGT) of rats by Huanglian Wendan Decoction from the perspective of the skeletal muscle Nod-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/interleukin-1β(IL-1β), interleukin-18(IL-18) pathway. Healthy male SD rats were fed with the diet containing 45% fat for 20 weeks, accompanied by a high-temperature and high-humidity environment and an inactive lifestyle, for the establishment of the IGT rat model. The rats were divided into the blank control group, model control group, metformin hydrochloride group(positive drug group, 0.05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group(7.8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks, the obesity and glycemic indexes of all the rats were measured. The fasting serum insulin(FINS) level was determined by ELISA, with the insulin sensitivity index(ISI) and insulin resistance index(IRI) calculated. The mRNA and protein expression le-vels of nuclear factor kappaB(NF-κB), NLRP3, caspase-1, IL-1β and IL-18 in skeletal muscle tissue were detected by real-time polymerase chain reaction(PCR), Western blot and immunofluorescence. Compared with the blank control group, the model control group witnessed significantly increased mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18. As revealed by the comparison with the model control group, Huanglian Wendan Decoction could effectively regulate the obesity status, reduce body weight, correct the abnormal levels of 2-hour plasma glucose(2 hPG), insulin resistance index(IRI), insulin sensitivity index(ISI), and lower the mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18 in the skeletal muscle tissue of IGT rats. Combined with previous studies, the above results showed that the occurrence and development of IGT was closely related to inflammatory response and the classic pyroptosis pathway in skeletal muscle, such as NLRP3/caspase-1/IL-1β, IL-18. It is inferred that the mechanism of Huanglian Wendan Decoction was to alleviate insulin resistance(IR) and then reverse the course of IGT lies in the regulation of the abnormal insulin receptor signaling pathway based on the NLRP3 inflammasome pathway.

Long-term effects of autogenous coronoid grafts on the facial growth of children with unilateral temporomandibular joint ankylosis and reconstructed mandibular condyle / 华西口腔医学杂志

OBJECTIVE@#Mandibular condyle injury usually results in malocclusion and disharmony of facial growth in growing children. This study aimed to evaluate the long-term effects of autogenous coronoid grafts on the facial growth of children with unilateral temporomandibular joint (TMJ) ankylosis who underwent mandibular condyle reconstruction.@*METHODS@#Ten growing patients with unilateral bony TMJ ankylosis admitted in West China Hospital of Stomatology, Sichuan University between January 1st, 2008 and December 31st, 2016 were followed up and evaluated. These patients include three males and seven females with ages ranging from 5 years to 12 years at the time of surgery. Each patient underwent gap arthroplasty, condyle reconstruction with ipsilateral coronoid, and interposition of the pedicled temporalis fascial flap in a single operation. The postoperative follow-up ranged from 3 years to 8 years with an average of 4.9 years. Postoperative panoramic radiographs determined the growth of the mandibular height and length on the affected side and compared it with those of the healthy side.@*RESULTS@#All patients recovered uneventfully after surgery. At the end of follow-up period, the maximal mouth opening ranged from 32 mm to 41 mm with an average of 35.6 mm. Mandibular height and length continued to grow after the successful treatment of ankylosis using autogenous coronoid grafts for condyle reconstruction. However, growth deficit still existed. The final ramus height and mandibular length of the affected side at the end of follow-up increased by 25.3% (P<0.05) and 26.1% (P<0.05), respectively, compared with the initial values measured immediately after surgery. Growth rates of ramus height and mandibular length of the affected side were 47.1% and 27.2% lower (P<0.05) than those of the healthy side, respectively.@*CONCLUSIONS@#Mandibular height and length continued to grow after the successful treatment of ankylosis by using autogenous coronoid grafts for condyle reconstruction. However, growth deficit still existed. The growth rate of the affected mandible was reduced compared with that of the undisturbed side even after treatment of ankylosis.

Application of Chen's pancreaticojejunostomy technique in laparoscopic pancreaticoduodenectomy (116 cases report) / 中华外科杂志

To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen's pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD). Clinical data of 116 consecutive patients who underwent LPD using Chen's pancreaticojejunostomy technique in Hunan Provincial People's Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen's pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed. All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes). The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2%(13/116) of cases had postoperative pancreatic fistula (POPF), including 10.3% (12/116) of biochemical fistula and 0.9%(1/116) of grade B POPF, no grade C POPF occurred; 10.3%(12/116) had gastrojejunal anastomotic bleeding; 3.4%(4/116) had hepaticojejunal anastomotic fistula; 3.4%(4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1%(14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7%(2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery. Chen's pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

Influence of nimodipine on neurological function ,serum levels of AQP4 and MIF in aged patients with hypertensive intracerebral hemorrhage / 心血管康复医学杂志

Objective :To study influence of nimodipine on neurological function and serum levels of aquaporin (AQP) 4 and macrophage migration‐inhibitory factor (MIF) in aged patients with hypertensive intracerebral hemorrhage (HICH).Methods :A total of 120 aged HICH patients treated in our hospital from Jan 2014 to Jan 2017 were ran‐domly and equally divided into routine treatment group (received puncture removal of hematoma + routine treat‐ment) and nimodipine group (received nimodipine based on routine treatment group ) ,both groups were treated for three weeks.United States National Institutes of Health Stroke Score (NIHSS) score ,brain edema volume ,serum levels of AQP4 ,MIF ,hsCRP and tumor necrosis factor (TNF)‐α ,therapeutic effect and incidence of adverse reac‐tion were measured and compared between two groups before and after treatment .Results :Total effective rate of nimodipine group was significantly higher than that of routine treatment group (88.33% vs .70.00%) , P＝0.013. Compared with routine treatment group after treatment ,there were significant reductions in NIHSS score [ (17.39 ± 3. 08) scores vs .(12. 26 ± 3.74) scores] ,brain edema volume [ (11. 84 ± 2.31) ml vs .(6.68 ± 1.93) ml] ,serum levels of AQP4 [ (2. 79 ± 0. 64) ng／ml vs .(1. 84 ± 0. 52) ng／ml] ,MIF [ (55.39 ± 7. 65) ng／L vs.(43.25 ± 5. 81) ng／L] ,hsCRP [ (18.83 ± 5. 17) mg／L vs.(12. 53 ± 3.87) mg／L] and TNF‐α [ (8. 42 ± 1.37) ng／L vs.(5. 78 ± 1.96) ng／L ] in nimodipine group , P＝0.001 all.There were no severe adverse reactions and no significant differ‐ence in incidence rate of adverse reactions between two groups , P＝0.436. Conclusion :Nimodipine can significantly improve therapeutic effect ,neurological function ,reduce serum AQP4 and MIF levels ,relieve brain edema and in‐flammation in aged HICH patients .

Strategy for development of fast-onset antidepressive agents: Candidate hypothesis of monoamine (5-HT)-nonmonoamine (Glu/GABA) long-feedback neural circuit / 中国药理学与毒理学杂志

Depression has become a serious global public health concern. Almost all the current first-line antidepressants developed are based on the classical "monoamine hypothesis (strategy)". These drugs commonly possess a series of defects, including slow-onset, lower response, cognitive injury and suicidal tendencies. So, by breaking through the classical monoamine strategy framework, developing new antidepressants with fast-onset, cognitive-enhancement and less adverse reactions is a major global demand. In 2019, fast-onset antidepressants S-ketamine(S-Ket) and brexanolone were approved by the FDA of USA, which opened up a new field for the non-monoamine strategy mainly based on the N-methyl-D-aspartic acid (NMDA) and y-aminobutyric acid A (GABAA) receptors. There are currently two main trends in the research and development of rapid onset antidepressants: the optimized multi-target monoamine strategy (modem monoamine strategy) and the non-monoamine strategy based on glutamate(Glu)-GABA balance regulation. According to the research of our laboratory and foreign colleagues, we propose a candidate hypothesis of the "monoamine (5-HT)-nonmonoamine (Glu/ GABA) long feedback neural circuit". It is believed that both monoamine regulatory mechanisms (such as 5-HT neurons located in raphe nucleus) and non-monoamine regulatory mechanisms (Glu/GABA neurons located in the prefrontal cortex and other brain regions) are all part of the rapid-acting antidepressant mechanisms, and both of them form a long-feedback neural loop mediating the fast synaptogenesis of the brain regions including the prefrontal cortex and hippocampus. Based on this hypothesis, we propose five candidate strategies for rapid onset of antidepressant development. (1) By relieving the inhibition of GABA interneurons on glutamatergic pyramidal neurons or directly activating glutamatergic pyramidal neurons, the rapid excitation/inhibition (E/l) balance can be achieved; (2) simultaneous regulation of 5-HT neuronal activity and E/l balance by 5-HT transporter and 5-HT receptors such as 5-HT1A (that means simultaneous enhancement of monoamine and nonmonoamine links); (3) direct activation of mammalian sirolimus (rapamycin) target protein complex 1 (mTORCI) and rapid enhance ment of the brain- derived neurotrophic factor (BDNF)- mTOR signaling; (4) stimulation of the fast release of BDNF in the brain; (5) positive allosteric modulator of GABAA receptor. We hope that these ideas and strategies will bring about a breakthrough for the development of a new generation of antidepressants in China in the future, and provide useful reference for further discovery of candidate targets for rapid antidepressant therapy.

Circular RNAs Regulate Cancer Onset and Progression via Wnt/β-Catenin Signaling Pathway

Cancer remains to be a major challenge for public health providers, and is the second leading cause of death worldwide. Therefore, it is imperative to explore the mechanisms underlying cancer initiation and development, and design novel diagnostics and therapeutics. Circular RNAs (circRNAs), which exhibit a covalently closed loop structure, are involved in a variety of diseases, including cancer. The aberrant expression of circRNAs contributes to the initiation and development of various cancers by disrupting the interplay of specific signaling pathways, including the Wnt/β-catenin pathway, which controls a plethora of cellular processes that drive cancer development. The interactions between circRNAs (specifically expressed in different cancer tissues) and Wnt/β-catenin signaling pathway presents potential diagnostic biomarkers and novel therapeutic targets. In this review, we have summarized research discoveries on the functions of Wnt/β-catenin pathway-related circRNAs in the modulation of oncogenesis and progression of different types of cancer. We anticipate that our findings will contribute to the improvement or development of circRNAs-based strategies for cancer treatment.

System for chiral antidepressant evaluation and related application / 中国药理学通报

Currently, most commercially available antidepres-sants have one or more chiral centers,and development of chiral antidepressants are of great interest for researchers. Thalidomide induced tragedy promotes drug evaluation centers from various countries to reevaluate their current guidelines and recommend single enantiomer application when developing a chiral antide-pressant. Unfortunately,as far to our knowledge,traditional en-antiomers comparison and active enantiomer selection are real-ized by simple comparison using in vitro targets data. Our team established an integrated system for chiral antidepressant evalua-tion and active enantiomer screening based on four modules,in-cluding pharmacodynamic comparison,pharmacokinetic compar-ison, toxicological comparison, and comprehensive factors. Here,we review this integrated system and make a detailed a-nalysis taking ammoxetine as a realistic example.

Application of the computer-assisted virtual reduction combined with 3D printing technique in acetabular fractures / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the computer-assisted virtual reduction combined with 3D printing technique as preoperative planning and assess their therapeutic effects.</p><p><b>METHODS</b>Thirty-five cases of acetabular fracture treated by internal fixation from March 2011 and March 2014 were retrospectively analyzed. All patients underwent operations with internal fixations implanted. The patients were divided into 2 groups according whether they used the computer-assisted virtual reduction combined with 3D printing technology. Fifteen patients in the digital group included 9 males and 6 females with a mean age of (39.4±8.8) years old ranging from 22 to 58 years old;time from injury to the operation was (8.8±2.0) days;for Letournel-Judet classification, 4 cases were both column fracture, 5 cases were posterior wall fracture, 4 cases were T-fracture, 2 cases were posterior wall with transverse fracture. Twenty cases in the control group included 12 males and 8 females with a mean age of (38.7±13.1) years old ranging from 19 to 59 years old;time from injury to the operation was(8.2±2.3) days;for Letournel-Judet classification, 6 cases were both column fracture, 8 cases were posterior wall fracture, 3 cases were T-fracture, 3 cases were posterior wall with transverse fracture. The volume of intraoperative blood loss and blood transfusion, operative time, satisfaction rate of fracture reduction and excellent and good rate of d`Aubigne Postal function evaluation were compared between the two groups and statistical analysis was conducted.</p><p><b>RESULTS</b>All the incisions healed without infection occurred. All the fractures healed without breakage or loosening of plates and screws. There was 1 case of postoperative nerve stimulation symptoms in each group. One patient in the digital group was found necrosis of the femoral head at 6 months after operation. One patient in the control group was found heterotopic ossification at 8 months after operation. All patients were follow-up for 13 to 28 months with an average of 17.6 months. The volume of intraoperative blood loss and blood transfusion in the digital group were significantly less than those in the control group(<0.05). The operation time in the digital group was shorter than that in the control group(<0.05). The excellent and good rates of fracture reduction were 92.9%(14/15) and 85%(17/20) in the digital group and the control group respectively, and there was no statistical significance (>0.05). The excellent and good rates of Aubigne Postal function evaluation were 86.7%(13/15) and 80%(16/20) respectively, and there was no significant difference(>0.05).</p><p><b>CONCLUSIONS</b>The computer-assisted virtual reduction combined with 3D printing technique can reduce the operative time, volume of intraoperative blood loss and blood transfusion in acetabular surgeries for patients with acetabular fractures. The technique is an effective method for preoperative planning, which worth promoting.</p>

Progress in potential targets for fast-onset antidepressants / 中国药理学与毒理学杂志

Depression has become a serious global public health concern and a prominent social problem.Moreover,the majority of first-line antidepressants that target monoamine neurotransmitter function have significant limitations (ie,low response rates,a time-lag of weeks for a response,cognitive impairment and sexual dysfunction),particularly with the delayed onset of clinical effects which will reduce the patients' clinical compliance and increase the patients' risk of suicide and self-harm.All this highlights a major unmet need for a new generation of antidepressants with fast onset action and low toxic side effects.There has been great progress in the study on pathogenesis of depression and drug targets so far.Recent research has shifted from increasing the level of monoamine neurotransmitter (NE/5-HT) to focusing on regulating the adaptive and plastic change of the nervous system,especially the discovery of new potential fast-onset non-monoaminergic targets including NMDA receptor,AMPA receptor and M choline receptor.This article reviews the investigation into generalized fast antidepressants and their potential targets,in the hope of providing critical information for the development of fastonset antidepressants.

Anti-post-traumatic-stress-disorder effects of YL-IPA08, a selective 18kDa translocator protein ligand / 国际药学研究杂志

Objective To explore the anti-post-traumatic-stress-disorder(anti-PTSD)effects of YL-IPA08,a selective 18kDa translocator protein(TSPO)ligand.Methods The time-dependent stress sensitization(TDS)method was used to establish a rat mod?el of PTSD.The open field test(OFT)was used to evaluate the locomotor activity in rats.The contextual freezing(CF)measurement, elevated plus maze(EPM)test and novel objective recognition(NOR)test were used to evaluate the PTSD-like behaviors in rats.The concentration of allopregnanolone in rat hippocampus was detected by ELISA. Results Compared with the control group,neither TDS nor drug treatment affected the locomotor activity in rats(P>0.05).However,PTSD rats showed significant PTSD-like behaviors with enhanced CF time in CF mearsurement,decreased open arm time and open arm entries in EPM test,and dropped object recogni?tion index in NOR test(P<0.05 or 0.01).Moreover,the concentration of hippocampus allopregnanolone was decreased in PTSD rats (P<0.05).YL-IPA08(0.05-0.1mg/kg)or positive drug sertraline(15 mg/kg),administered intragastrically after establishment of PTSD model,significantly reversed the above PTSD-like behavioral changes(P<0.05 or 0.01)and increased the concentration of hip?pocampus allopregnanolone in PTSD rats.Conclusion YL-IPA08 could improve the PTSD-like behavior in rats,and the mechanism may be related to the increased allopregnanolone level in hippocampus.

Preparation and evaluation of new cyanoacrylate nanosphere with alcoxyle side group for gene delivery / 国际药学研究杂志

Objective To prepare a new(alcoxyle cyanoacrylate)-based nanosphere for brain targeting gene delivery and evaluate its physicochemical properties,capability of delivery of transforming growth factor beta 2(TGF-β2)antisense oligonucle?otides(ASON),and its potential use on tumor cell suppression in vitro.Methods The cationic nanospheres(NS)were prepared by emulsion polymerization method with DEAE-dextran as cationic stabilizer.The ASON were adsorbed by charge interaction,and poly?sorbate-80 was used as brain-targeting modification.The morphology was observed by transmission electron microscopy(TEM).The average particle size and Zeta potential were determined by dynamic light scattering(DLS). The ultraviolet spectrophotometry was used to determine the entrapment efficiency and drug loading.Agarose gel electrophoresis was used to analyze the optimal loading ratio of ASON-NS,and also the protection of ASON in DNaseⅠand serum containing environment.The release rate of ASON was deter?mined by dialysis.The cytotoxicity on L929 cells and the anti-tumor activity on A172 cells were evaluated by MTS.Results The TEM showed a typical round nanospheres morphology,and no adhesion was detected.The particle size was(79.04±4.33)nm,the disper?sion coefficient was 0.04 ± 0.03,the Zeta potential was(33.60 ± 0.60)mV. The encapsulation efficiency of ASON-NS was(83.14 ± 1.90)%,and the drug loading of ASON-NS was(11.59±0.56)%.The NS provided ASON protection against the Dnase I and serum containing environment. The NS-ASON could effectively deliver ASON into A172 cells and show anti-tumor activity. Besides,little L929 cytotoxicity was detected.Conclusion A new cyanoacrylate nanosphere with alcoxyle side group for brain targeting gene deliv?ery was prepared successfully. It had good ASON loading and delivery capability,providing new carrier materials for nucleic acid drugs.

Translocator protein mediated anti-PTSD effects of YL-IPA08 / 军事医学

Objective To explore the role of 18 ku translocator protein (TSPO) in the anti-post-traumatic-stress-disorder(PTSD) effects of YL-IPA08 and the value of TSPO as a potential pharmacological target using gene knock out mice.Methods The PCR method was used to genotype TSPO wild type (WT) mice and knock out (KO) mice.Foot shock was used to establish a well-accepted mouse model of PTSD,the open field test (OFT) was used to evaluate the locomotor activity in mice,and freezing measurement was used to evaluate the PTSD-like fear behavior in mice.Results Compared with TSPO WT mice,KO mice had no expressible TSPO gene,but showed similar locomotor activity to WT mice after PTSD modeling.On day 1,day 5 and day 16 after PTSD modeling (day-1-day 0),both WT and KO mice showed significant PTSD-like behavior with enhanced freezing time.However,8 d treatment (day 0-day 7) of YL-IPA08 (0.3 mg/kg,once daily) or positive drug sertraline (15 mg/kg,once daily) after PTSD modeling significantly reduced freezing time selectively in WT mice,but not in KO mice.Conclusion It has been found for the first time that TSPO WT and KO mice can show the same sensitivity to PTSD modeling (namely the same PTSD-like behavior performance).Interestingly,TSPO can mediate the anti-PTSD effects of YL-IPA08.Therefore,the present study provides direct evidence for the value of TSPO as an potential pharmacological target for PTSD.

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD).</p><p><b>METHODS</b>The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition.</p><p><b>RESULTS</b>Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis.</p><p><b>CONCLUSIONS</b>Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.</p>

Application of rafting K-wire technique for tibial plateau fractures / 中国骨伤

<p><b>OBJECTIVE</b>To summarize application of rafting K-wires technique for tibial plateau fractures.</p><p><b>METHODS</b>From January 2013 to January 2015,45 patients with tibial plateau fractures were treated by locking plate with rafting K-wires, including 33 males and 12 females with an average of 44.2 years old ranging from 22 to 56 years old. According to Schatzker classification, 6 cases were type II, 8 were type Ill, 4 were type IV, 4 were type V, and 5 were type VI. Allogeneic bone graft were performed for bone defects. All patients were fixed with two to five K-wires. Part of weight loading were encouraged at 3 months after operation,and full weight-loading were done at 5 months after operation. Postoperative complications were observed,and Rasmussen clinical and radiological assessment were used to evaluate clinical results.</p><p><b>RESULTS</b>All Patients were followed up from 10 to 23 months with average of 14 months. According to Rasmussen clinical and radiological assessment, clinical scores 23.58 ± 6.33, radiological scores were 14.00 ± 6.33; and excellent and good rates were 82.2% and 77.8% respectively. Four patients occurred severe osteoporosis and collapse of articular surface; 5 patients occurred traumatic arthritis.</p><p><b>CONCLUSION</b>Rafting K-wires technique with anatomized armor plate could effective fix and support platform collapse and joint bone fragments, increase support surface area and reduce postoperative reduction loss rate.</p>

Comparative study on the correlation of penetrating keratoplasty rejection with different cornea preservation methods / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To understand the relation between the penetrating keratoplasty rejection and the methods of cornea preservation. METHODS: The 30 Wistar rats as donator and 60 SD rats as receptor were used to establish the animal models of penetrating keratoplasty rejection. And 60 SD rats were randomly divided into 3 groups. Donor cornea of Wistar rats preserved in different methods were used separately in 3 groups. The penetrating keratoplasty rejection index ( RI ) , means survival time ( MST ) of corneal grafts and pathological changes in post -operation were analyzed. RESULTS: The MST was ( 10. 4±1. 70 ) d in moist-chamber- preserved group (Ⅰ), ( 12. 9 ± 1. 81 ) d in medium-term-preserved group (II) and (16. 1±2. 57) d in cryopreserved group ( Ⅲ) . The MST in the cryopreserved group was evidently prolonged, showing a significant correlation compared with other two groups (PCONCLUSION: The postoperative rejection of penetrating keratoplasty in rats is decreased and rejection time is delayed in cryopreserved cornea.

Clinical research of protein-free calf blood extract eye gel for corneal epithelial defect / 国际眼科杂志(Guoji Yanke Zazhi)

AlM: To evaluate the clinical effect of 200g/L protein-free calf blood extract eye gel for corneal epithelial defect.METHODS: One hundred and sixty - eight cases of corneal epithelial defect ( 58 cases with herpes simplex keratitis; 24 cases with chemical injury; 85 cases with pterygium operation injury ) were randomly divided into two groups: 84 eyes were treated with protein-free calf blood extract eye gel; 84 cases were treated with basic fibroblast growth factor eye gel ( bFGF ) . The bFGF and protein-free calf blood extract eye gels were used 4 times a day. The treatment course was 7d. Epithelial defect restoration, local symptom and sign were observed. RESULTS: The difference between pre-treatment and post-treatment was significant ( P CONCLUSlON: Protein-free calf blood extract eye gels is valuable and safe for corneal epithelial defect.

Neuropsychiatric disorders and cognitive dysfunction in patients with Cushing's disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the main neuropsychiatric disorders and cognitive deficits in patients with Cushing's disease (CD) and the associated pathophysiological mechanisms underlying CD. These mechanistic details may provide recommendations for preventing or treating the cognitive impairments and mood disorders in patients with CD.</p><p><b>DATA SOURCES</b>Data were obtained from papers on psychiatric and cognitive complications in CD published in English within the last 20 years. To perform the PubMed literature search, the following keywords were input: cushing's disease, cognitive, hippocampal, or glucocorticoids.</p><p><b>STUDY SELECTION</b>Studies were selected if they contained data relevant to the topic addressed in the particular section. Because of the limited length of this article, we have frequently referenced recent reviews that contain a comprehensive amalgamation of literature rather than the actual source papers.</p><p><b>RESULTS</b>Patients with active CD not only suffer from many characteristic clinical features, but also show some neuropsychiatric disorders and cognitive impairments. Among the psychiatric manifestations, the common ones are emotional instability, depressive disorder, anxious symptoms, impulsivity, and cognitive impairment. Irreversible effects of previous glucocorticoid (GC) excess on the central nervous system, such as hippocampal and the basal ganglia, is the most reasonable reason. Excess secretion of cortisol brings much structural and functional changes in hippocampal, such as changes in neurogenesis and morphology, signaling pathway, gene expression, and glutamate accumulation. Hippocampal volume loss can be found in most patients with CD, and decreased glucose utilization caused by GCs may lead to brain atrophy, neurogenesis impairment, inhibition of long-term potentiation, and decreased neurotrophic factors; these may also explain the mechanisms of GC-induced brain atrophy and hippocampal changes.</p><p><b>CONCLUSIONS</b>Brain atrophy and hippocampal changes caused by excess secretion of cortisol are thought to play a significant pathophysiological role in the etiology of changes in cognitive function and psychiatric disturbances. The exact mechanisms by which GCs induce hippocampal volume loss are not very clear till now. So, further investigations into the mechanisms by which GCs affect the brain and the effective coping strategy are essential.</p>