[Research progress on robot-assisted subretinal and intravascular injection surgeries].

Various retinal diseases require subretinal and/or intravascular injections, which are precise and challenging ocular microsurgeries. Robot-assisted surgery is expected to promote surgery precision, visualization, and success rates. This review summarizes recent research progress on robot-assisted surgery for subretinal and intravascular injections, emphasizing effectiveness, safety, and intelligence, and aiming to provide valuable insights for research on the application of surgical robots in the treatment of retinal diseases.

[Analysis of 15 cases of trench foot in peacetime].

Trench foot was first seen in World War Ⅰ and was one of the reasons for non combat attrition. We reviewed and analyzed 15 cases of trench foot admitted from 2010 to 2021, summarized clinical treatment methods and experiences, analyzed the causes, population characteristics, treatment methods, and treatment experiences of trench foot during peacetime, strengthened attention to high-risk groups, and improved the success rate of clinical treatment.

[Analysis of unplanned reoperation following vitreoretinal surgery].

Objective: To determine the incidence of unplanned reoperation following vitreoretinal surgery and identify the reasons for unplanned reoperations. Methods: Case records of all patients undergoing vitreoretinal surgery at Peking Union Medical College Hospital between June 2014 and June 2017 were reviewed to determine the incidence of unplanned reoperations during the primary admission and within 90 days following vitreoretinal surgery. Results: A total of 3 356 case records were reviewed. During the primary admission, 97 times of unplanned reoperation occurred in 81 cases [45 males and 36 females, aged (47.3±16.8) years].The incidence of unplanned reoperation was 2.4% (81/3 356). The most common primary diseases were retinal detachment (25 cases, 30.9%), proliferative diabetic retinopathy (23 cases, 28.4%) and silicone oil filled eye (17 cases, 21.0%). The most common reasons for unplanned reoperation were new onset or recurrent retinal detachment (33 times, 34.0%), increased intraocular pressure (23 times, 23.7%), as well as hyphema and inflammation (16 times, 16.5%). The percentages of the primary diseases and reasons for unplanned reoperation within 90 days following vitreoretinal surgery were not significantly different when compared with those during the primary admission. Desired results could be achieved in all cases after unplanned reoperation. Conclusions: The primary diseases of unplanned reoperation for vitreoretinal surgery are complicated retinal detachment, diabetic retinopathy and silicone oil filled eyes. New onset or recurrent retinal detachment, increased intraocular pressure, hyphema and inflammation are common causes of reoperation.

Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China.

BACKGROUND: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. RESULTS: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

RETRACTED: Modulation of macrophage phenotype through controlled release of interleukin-4 from gelatine coatings on titanium surfaces.

Pro-inflammatory phenotype (M1) macrophages initiate angiogenesis, while their prolonged activation can induce chronic inflammation. Anti-inflammatory phenotype (M2) macrophages promote vessel maturation and tissue regeneration. Biomaterials which can promote M2 polarisation after appropriate inflammation should enhance angiogenesis and wound healing. Herein, Interleukin-4 (IL-4), an anti-inflammatory cytokine, was adsorbed onto a titanium surface. Then, a genipin cross-linked gelatine hydrogel was coated onto the surface to delay IL-4 release. The cross-linking degree of the hydrogel was modulated by the different amount of genipin to control release of IL-4. When 0.7 wt% (weight %) genipin was used as a cross-linker, the sample (GG07-I) released less IL-4 within the first several days, followed by a sustained release time to 14 d. Meanwhile, the release rate of IL-4 in GG07-I reached a peak between 3 d and 7 d. In culture with macrophages in vitro, GG07-I and GG07 exhibited good cytocompatibility. The phenotypical switch of macrophages stimulated by the samples was determined by FACS, ELISA and PCR. Macrophages cultured with GG07-I, GG07 and PT were firstly activated to the M1 phenotype by interferon-gamma (IFN-γ). Then, due to the release of IL-4 in 5 to 7 d, GG07-I enhanced CD206, increased the secretion and gene expression of M2 marker, such as interleukin-10 (IL-10), arginase-1 (ARG-1) and platelet derived growth factor-BB (PDGF- BB). GG07-I prompted the switch from M1 to M2 phenotype. Those appropriate secretion of cytokines would benefit both vascularisation and osseointegration. Thus, the biomaterial directing inflammatory reaction has good prospects for clinical treatments.

[Prevalence and risk factors of diabetic retinopathy in hospital patients].

Objective: To analyze the prevalence and risk factors of diabetic retinopathy (DR) in ophthalmic patients. Methods: A cross-sectional study was performed. Diabetic patients who were admitted to Department of Ophthalmology, Traditional Chinese Medicine Hospital of Muping between October 2012 and June 2013 were included. General information and medical history were obtained from each subject by questionaires. Laboratory and detailed ophthalmic examinations were performed during the study. DR was diagnosed and graded by mydriatic fundus photography. Prevalence of DR was calculated and logistic regression was used to analyze the relationship between DR and various factors. Results: A total of 676 diabetic patients were included, and 455 of them presented with DR at a morbidity rate of 67.31%. Among DR patients, the number of mild, moderate, severe non-proliferative diabetic retinopathy (NPDR) patients and proliferative diabetic retinopathy (PDR) patients were 211 (46.37%), 167 (36.70%), 57 (12.53%) and 20 (4.40%), respectively. There was no significant difference in the prevalence of DR among different age groups (χ(2)=6.527, P=0.089). However, there was a significant difference between different disease duration groups (χ(2)=39.401, P<0.001), as well as between insulin therapy group and non-insulin therapy group (χ(2)=7.378, P=0.007). The multivariate logistic regression analysis demonstrated the independent risk factors for DR occurrence were hemoglobin A1c (HbA1c) (OR=1.131, 95%CI: 1.022-1.252, P=0.011) and duration of diabetes (OR=1.077, 95%CI: 1.046-1.108, P<0.001). Conclusions: The prevalence of DR in ophthalmic patients was associated with duration of diabetes, HbA1c, obesity, smoke, nephropaty and insulin therapy. Increased HbA1c level and longer duration of diabetes were independent risk factors for DR in diabetic patients.

[Oblique puncture approach via anterolateral to C2: a study of imaging anatomy on corpses].

Objective: To determine the anatomical relation between the carotid artery or laryngopharynx and the needle path via anterolateral oblique approach to C2 vertebral body, and whether the simulated path can direct the actual procedure. Methods: Contrast agent was injected into bilateral carotid arteries of 10 fresh cadavers (20 sides), and then CT scans were performed on each subject. Bilateral simulated puncture paths were simulated on the image of two-dimensional reconstruction CT. The distance between the puncture site and middle line(AC), the angle between the simulated puncture paths and the median sagittal plane (AOB), the distance between the simulated puncture paths and the side wall of hypopharynx, or the carotid artery was measured respectively. Under the guidance of fluoroscopy, oblique puncture via anterolateral to C2 was performed according to the simulated parameters, and then CT was done. The actual needle path was measured on the image of two-dimensional reconstruction CT. The outcomes were compared by using paired t test between groups. Results: Bilateral simulated puncture paths in all 10 cadavers were achieved on the image of CT. The bilateral punctures via anterolateral to C2 were successfully performed under fluoroscopic guidance in 10 cadavers, and the actual needle path could be showed on the image of two-dimensional reconstruction CT. The AC, angle AOB, the distance to carotid artery and side wall of laryngopharyngeal of the left simulated path was(4.7±1.0)cm, (33±8)°, (6.7±2.6)mm, (6.6±2.8)mm, respectively; and those in the right side was(5.2±1.3) cm, (36±8)°, (7.5±2.2) mm, (7.2±2.5) mm, respectively.The AC, angle AOB, the distance to carotid artery and side wall of laryngopharyngeal of the left actual needle was(4.5±1.1) cm, (33±9) °, (6.7±3.0) mm, (7.1±3.9) mm, respectively; and those in the right side was(5.1±1.5) cm, (35±10) °, (7.4±2.1) mm, (7.2±2.6) mm, respectively.And the actual and simulation data of both sides were compared and no significant differences was found by t test (t=0.104-1.882, all P>0.05). Conclusion: The simulated approach via anterolateral to C2 can be achieved on the image of two-dimensional reconstruction CT, it is consistent with the real needle path and can be used to direct the actual practice to improve the accuracy and safety.

[Clinical effect and safety of 144-week treatment with entecavir capsules in treatment-naïve HBeAg-positive patients with chronic hepatitis B].

Objective: To investigate the clinical effect and safety of entecavir capsules in the treatment of treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). Methods: A total of 158 HBeAg-positive CHB patients were given oral entecavir capsules at a dose of 0.5 mg/time once a day for 144 weeks. Clinical outcome and safety were evaluated at baseline and at 24, 48, 72, 96, 120, and 144 weeks of treatment respectively. The Fisher's exact test was used for the analysis of categorical data. Results: After 144 weeks of treatment, 90.91% of all patients achieved virologic response (< 69 IU/ml), the normalization rate of alanine aminotransferase was 88.18%, the clearance rate of HBeAg was 33.33%, and the seroconversion rate of HBeAg was 24.07%. Of all patients, 2 dropped out due to adverse events and 5 experienced serious adverse reactions. Conclusion: Entecavir capsules can inhibit viral replication and have good safety in treatment-naïve HBeAg-positive CHB patients.

The change of plasma pituitary adenylate cyclase-activating polypeptide levels after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Elevated circulating pituitary adenylate cyclase-activating polypeptide (PACAP) levels have been demonstrated to be associated with clinical outcomes of severe traumatic brain injury. The current study aimed to confirm whether elevated plasma PACAP levels are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: One hundred and eighteen aSAH patients and 118 controls were recruited. Plasma PACAP concentrations were determined using enzyme-linked immunosorbent assay. Patients were followed up until death or completion of 6 months after aSAH. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. RESULTS: The admission PACAP levels were significantly elevated in all patients (296.6 ± 119.7 pg/ml) compared with controls (77.1 ± 17.9 pg/ml, P < 0.001). Plasma PACAP levels were independently associated with clinical severity indicated by World Federation of Neurological Surgeons (WFNS) score (t = 4.745, P < 0.001) and Fisher score (t = 4.239, P < 0.001) using a multivariate linear regression. PACAP was identified as an independent predictor for 6-month mortality [odds ratio (OR), 1.014; 95% confidence interval (CI), 1.005-1.030; P < 0.001] and 6-month unfavorable outcome (OR, 1.012; 95% CI, 1.006-1.028; P < 0.001) and 6-month overall survival (hazard ratio, 1.016; 95% CI, 1.008-1.023; P < 0.001) using a binary logistic regression analysis and a Cox's proportional hazard analysis, respectively. PACAP had similar predictive values compared with WFNS score and Fisher score according to the receiver operating characteristic curve analysis. CONCLUSIONS: Higher plasma PACAP levels are associated with clinical severity and long-term prognosis of aSAH patients, and PACAP has potential to be a good prognostic biomarker of aSAH.

Genetic variability of ERCC1 and ERCC2 influences treatment outcomes in gastric cancer.

We performed a study to investigate the role of ERCC1 (rs11615, rs2298881, and rs3212986) and ERCC2 (rs13181, rs238406, and rs1799793) polymorphisms in the prognosis of gastric cancer. A total of 346 patients with gastric cancer were recruited between May 2009 and May 2012. Single nucleotide polymorphism genotyping was performed using the Sequenom MassARRAY platform. The GA+AA genotype of ERCC2 rs1799793 showed significant and favorable response to chemotherapy than the wide-type GG genotype in multivariate analysis (OR = 1.78, 95%CI = 1.13-2.81). In a Cox proportional hazard model, carriers of ERCC2 rs1799793 GA+AA genotype exhibited longer duration of survival than did those with the GG genotype (hazards ratio = 0.57, 95%CI = 0.35-0.92). In conclusion, our study suggests that ERCC2 rs1799793 polymorphic variation could be used as a predictor for the prognosis of gastric cancer.

A novel mutation of PAX6 identified in a Chinese twin family with congenital aniridia complicated with nystagmus.

Genetic variations within the paired box gene 6 (PAX6) gene are associated with congenital aniridia. To detect the genetic defects in a Chinese twin family with congenital aniridia and nystagmus, exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Six members from the family of three generations were included in the study. The twins' father presented with congenital aniridia, nystagmus and cataract at birth, while the twins presented with congenital aniridia and nystagmus. A novel mutation c.888 insA in exon 10 of PAX6 was identified in all affected individuals. This study suggests that the novel mutation c.888 insA is likely responsible for the pathogenesis of the congenital aniridia and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation in PAX6 gene in pedigree with aniridia. Furthermore, no PAX6 gene defect was reported in twins with congenital aniridia.

Protective effect of oleanolic acid against beta cell dysfunction and mitochondrial apoptosis: crucial role of ERK-NRF2 signaling pathway.

Pancreatic beta cell dysfunction is a hallmark of diabetes. Our previous results have shown that oleanolic acid (OA) has anti-diabetic potential. However, there is little literature reporting the effect of OA on beta cell dysfunction. The present study was designed to investigate the protective effect of OA against lipotoxicity and the underlying mechanisms. Lepr (db/db) diabetic mice were subjected to fasting blood glucose measurement, intraperitoneal glucose tolerance test after the administration of OA for two weeks. Histopathological observation was conducted by HE staining and transmission electron microscopy assay. Pancreatic islets were isolated from db/db diabetic mice and C57BL/6J mice. Palmitic acid (PA) was used to induce lipotoxicity in vitro. Apoptosis was evaluated in pancreatic islets in diabetic mice and in isolated pancreatic islets and beta-TC3 cells by TUNEL assay. Cellular ATP content, mitochondrial function and redox balance were examined. Phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) and the activation of nuclear erythroid factor 2 p45-related factor 2 (Nrf2) signaling were evaluated by western blotting. In db/db mice, OA significantly protects beta cell function against lipotoxicity, evidenced by inhibition of apoptosis and improvement of glucose tolerance. In cells, OA administration may protect against PA-induced apoptosis and decrease of GSIS, in which process the activation of Nrf2 is essential. Once Nrf2 is activated, OA could induce GCLc expression, promote the production of GSH, and thus inhibit JNK phosphorylation and solid the antioxidant defense of mitochondria, leading to the inhibition of mitochondrial apoptosis. ERK signaling pathway is responsible for OA-induced activation of Nrf2 and the protective effect of OA. Overall, our study enhances the understanding of the protective effect of OA on beta cell and provides clues for further studies on the underlying mechanisms.

Plasma resistin, associated with single nucleotide polymorphism -420, is correlated with C-reactive protein in Chinese Han patients with spontaneous basal ganglia hemorrhage.

We examined a possible relationship -420C>G SNP of the resistin gene with plasma resistin and C-reactive protein concentrations in intracerebral hemorrhage. Three hundred and forty-four Chinese Han patients with intracerebral hemorrhage and 344 age- and gender-matched healthy controls were included in our study. Plasma resistin and C-reactive concentrations were measured and SNP -420C>G was genotyped. The genotype frequencies in controls and patients were not significantly different (P = 0.672). Plasma resistin and C-reactive protein levels were significantly different between the SNP -420C>G genotypes, even after adjustment for age, gender and body mass index. The common homozygote (C-C) had the lowest resistin and C-reactive protein plasma concentrations; the plasma resistin and C-reactive protein concentrations in the heterozygote (C-G) and the rare allele homozygote (G-G) did not differ significantly. Plasma resistin levels were significantly associated with plasma C-reactive protein level. We conclude that SNP -420C>G of the resistin gene could be involved in the inflammatory component of intracerebral hemorrhage through enhanced production of resistin.

[Clinical effect and analysis of exercise treatment for temporomandibular joint osteoarthritis].

Objective: To explore the clinical efficacy of (stomatognathic system functional exercise(SSFE) in the treatment of temporomandibular joint osteoarthritis (TMJOA), and to provide reference for the clinical treatment of TMJOA. Methods: Choose between January 2020 and June 2020 in the Affiliated Hospital of Qingdao University of Temporomandibular Disorder (TMD) Clinics, pain in the temporomandibular joint (TMJ), limited openings for complained of symptoms of TMD patients, diagnosed by clinical examination and cone beam CT (CBCT) examination of TMJOA patients 60 patients (64 joints), including 20 males and 45 females, the age was (42.6±2.5) years (33-47 years old). The patients were randomly divided into the experimental group (30 cases, 34 joints) and the control group (30 cases, 30 joints) according to the odd and even numbers of their treatment numbers. The experimental group was treated with SSFE method. The control group was treated with maxillary full dentition occlusal splint. Visual analogue score (VAS), natural mouth opening and maximal mouth opening (MMO) of each patient in each group were recorded at initial diagnosis, 2 weeks, 3 and 6 months after treatment, and CBCT imaging was compared for the changes of condylar bone at initial diagnosis, 3 and 6 months after treatment. Results: VAS values of the experimental groups were (2.90±1.42), (0.90±0.37), (0.87±0.23) at 2 weeks, 3 and 6 months after treatment, respectively. The VAS values of the control group were (4.57±1.94), (4.17±2.09), (3.73±2.21), respectively. The VAS score of the experimental group was significantly lower than that of the control group (F=42.93, P<0.001). Before SSFE treatment, all the patients in the experimental group had different degrees of restricted opening and characteristic abnormal opening and closing pattern. Two weeks after SSFE treatment, the opening degree of the patients was (37.69±2.4)mm, the opening shape "↓" and the closing shape "↑" were normal. At 3 and 6 months after treatment, the oral opening was (38.98±1.08) mm and (39.73±1.76) mm, respectively. The opening degree of control group was (36.85±2.33) mm 2 weeks after treatment, and the characteristic abnormal opening and closing pattern still existed. The opening degree of control group was (37.82±1.85) mm and (37.40±1.75) mm 3 and 6 months after treatment, respectively. The characteristic abnormal opening and closing pattern (stuffy, awkward, deliberate, unnatural) did not improve significantly. The openness of the experimental group was significantly higher than that of the control group (F=25.20, P<0.001). In the experimental group, 82.4% (28/34) had benign remodeling of condylar bone 6 months after treatment, and 17.6% (6/34) had no change of condylar bone. There was no significant change in condylar bone in control group. CBCT scores of the experimental group were (2.43±1.74) and (1.70±1.26) at 3 and 6 months after treatment, respectively. CBCT scores of the control group at 3 and 6 months after treatment were (4.23±1.50) and (4.10±1.37), they were significantly lower in the experimental group than in the control group (F=27.20, P<0.001). Conclusions: Full dentition occlusal splint can alleviate the pain in the joint area of TMJOA patients, but can not improve the characteristic abnormal mandibular movement, and the condyle bone repair is not obvious. SSFE can effectively relieve the symptoms and signs of TMJOA patients, especially improve the abnormal characteristic mandibular movement, and promote the normal reconstruction and repair of condylar bone.

[Feasibility analysis of immediate implant placement in the maxillary molar region].

Objective: To study the clinical outcomes and feasibility of immediate implantation after flap surgery and minimally invasive extraction in the maxillary molar area and to provide a reference for it. Methods: Forty-one patients (41 molars in total) with maxillary molars that could not be preserved, treated from June 2018 to June 2020 at the Department of Oral and Maxillofacial Surgery at the Affiliated Hospital of Qingdao University, were selected. There are 24 males and 17 females with the age of (49.7±1.8) years (range 18-66 years). Pre-operative cone-beam CT (CBCT) was taken for measurement and analysis. After flap surgery and minimally invasive tooth extraction, the inflammatory granulation tissues attached to the soft and hard tissues were completely scraped and clipped, followed by the preparation of the implants in the correct three-dimensional position. Torque value and implant stability quotient (ISQ) were recorded after implant placement and with non-submerged healing. CBCT examination was taken 6 months after surgery and ISQ value was checked before crown restoration. CBCT examination was also taken 1 year after the permanent restoration. The survival rate of 6 months after surgery, the success rate of 1 year after permanent restoration, and the size of jump gaps immediately after surgery, 6 months after surgery, 1 year after permanent restoration respectively, were performed. The ISQ values were compared immediately and 6 months after surgery. Results: A total of 41 implants were placed in 41 patients. Six months after surgery, the survival rate was 100% (41/41). Twelve months after permanent restoration, the success rate of the implant restoration was 100% (41/41). The torque value after implant implantation was (42.77±0.79) N·cm. The buccal and palatal jump gaps were (3.15±0.16) mm and (2.86±0.18) mm immediately after surgery, respectively. The mesial and distal jump gaps were (2.94±0.19) mm and (3.77±0.21) mm, respectively. CBCT showed that no jump gap around the implants at 6 months after surgery and 1 year after permanent restoration. The ISQ values at immediately and 6 months after surgery were (74.78±0.59) and (80.20±0.49) respectively, and the difference was statistically significant (t=-9.03, P<0.001). Conclusions: Immediate dental implantation in the correct three-dimensional position could achieve good osseointegration by means of flap surgery, minimally invasive extraction and thorough removal of inflammatory tissue on the surface of soft and hard tissues. The clinical outcomes were satisfactory.

Time course of plasma microparticle concentrations after acute spontaneous basal ganglia hemorrhage.

OBJECTIVES: To examine the changes in plasma microparticle (MP) levels in patients after intracerebral hemorrhage (ICH) and assess their association with outcome along with biological markers of the acute phase response. MATERIALS AND METHODS: Thirty healthy controls and 86 patients with acute ICH were recruited. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. MPs with procoagulant potential were measured with a prothrombinase assay. RESULTS: Plasma MP levels in patients were substantially higher than those in healthy controls during the 7-day period. Plasma MP levels were strongly associated with outcome and with biological markers of the acute phase response. Multivariate analysis showed baseline plasma MP level was a good predictor of 1-week mortality (odds ratio, 1.930; 95% confidence interval, 1.229-3.031; P=0.004). A receiver operating characteristic curve identified the plasma MP cutoff level (8.4 nmol/l phosphatidylserine equivalent) that predicted 1-week mortality with high sensitivity (90.6%) and specificity (68.5.0%) (P<0.001). CONCLUSIONS: Increased membrane microparticle levels occur after ICH and may contribute to the subsequent brain injury, in association with a poor clinical outcome.

Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity.

Recent evidence suggests that one mechanism whereby cytotoxic drugs, such as doxorubicin, kill tumors is the induction or up-regulation of Fas ligand (FasL) expression on the tumor cell surface. The ensuing engagement of Fas by FasL on adjacent cells leads to apoptosis. However, despite cytotoxic drug-induced FasL expression, Fas-sensitive tumors frequently resist chemotherapy, suggesting that they may possess a mechanism that prevents or inactivates Fas-FasL interactions. In the present work, we addressed the involvement of the FasL/Fas signaling pathway in doxorubicin-induced apoptosis and the ability of matrix metalloproteinases (MMPs) to proteolytically cleave FasL in tumor cells. Doxorubicin-induced apoptosis was inhibited by expression of soluble Fas or incubation of the tumor cells with MMP-7 but not with MMP-2 or MMP-9. Resistance to doxorubicin was also induced by expression in the tumor cells of constitutively active MMP-7 but not of a catalytically inactive mutant. Conversely, inhibition of MMP-7 expression in tumor cells by transfection of MMP-7 cDNA in antisense orientation resulted in sensitization to doxorubicin. MMP-7 efficiently cleaved recombinant FasL in vitro and reduced cell surface FasL expression. Our observations provide evidence that one mechanism whereby MMP-7 may promote tumor survival and resistance to doxorubicin is by cleaving FasL and reducing its effectiveness in triggering Fas-mediated apoptosis.

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.

Non-fibrillar soluble oligomeric forms of amyloid-ß peptide (oAß) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAß initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aß, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAß levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAß to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aß on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aß and tau pathology.

S100beta interaction with tau is promoted by zinc and inhibited by hyperphosphorylation in Alzheimer's disease.

The zinc-binding protein S100beta has been identified as an interacting partner with the microtubule-associated protein tau. Both proteins are individually affected in Alzheimer's disease (AD). S100beta, is overexpressed in the disease, whereas hyperphosphorylated tau constitutes the primary component of neurofibrillary tangles. In this study, we examine factors that modulate their binding and the potential role the complex may play in AD pathogenesis. Zinc was identified as a critical component in the binding process and a primary modulator of S100beta-associated cellular responses. Abnormally phosphorylated tau extracted from AD tissue displayed a dramatically reduced capacity to bind S100beta, which was restored by pretreatment with alkaline phosphatase. In differentiated SH-SY5Y cells, exogenous S100beta was internalized and colocalized with tau consistent with an intracellular association. This was enhanced by the addition of zinc and eliminated by divalent metal chelators. S100beta uptake was also accompanied by extensive neurite outgrowth that may be mediated by its interaction with tau. S100beta-tau binding may represent a key pathway for neurite development, possibly through S100beta modulation of tau phosphorylation and/or functional stabilization of microtubules and process formation. S100beta-tau interaction may be disrupted by hyperphosphorylation and/or imbalances in zinc metabolism, and this may contribute to the neurite dystrophy associated with AD.

Ultrasonic dissection versus conventional electrocautery during gastrectomy for gastric cancer: a meta-analysis of randomized controlled trials.

OBJECTIVE: Use of ultrasonic surgical instrument is gaining popularity for dissection and coagulation in open surgery. However, there is still no consensus on the efficacy and safety of its use compared with conventional surgical technique in open gastrectomy for gastric cancer. The aim of this meta-analysis was to evaluate the role and surgical outcomes of ultrasonic dissection (UD) compared with conventional electrocautery (EC). METHODS: A systematic literature search was performed to identify all studies comparing UD and EC in gastric cancer surgery. Intraoperative and postoperative outcomes were compared using weighted mean differences (WMDs) and odds ratios (ORs). RESULTS: Five studies were included in this meta-analysis, comprising 489 patients. Meta-analysis results showed that compared with EC, UD was associated with significantly shorter operation time (P = 0.03), less intraoperative blood loss (P = 0.002), lower morbidity (P = 0.02), and reduced postoperative hospital stay (P = 0.03). However, there was no significant difference between the two surgical techniques with regards to postoperative abdominal drainage (P = 0.17), and total cost in hospital (P = 0.59). CONCLUSIONS: Compared to EC, the use of UD during open gastrectomy can provide several improved outcomes for operation time, intraoperative blood loss, overall morbidity, and postoperative hospital stay. It appears that UD can be used instead of conventional EC in open gastric cancer surgery, although more larger trials with long follow-up should be performed.