Lysine succinylation is a novel post-translational modification, which plays an important role in regulating distinct cellular functions control, therefore it is necessary to accurately identify succinylation sites in proteins. As traditional experiments consume material and financial resources, prediction by calculation is an efficient method being proposed recently. In this study, we developed a new prediction method iSucc-PseAAC, which uses a variety of classification algorithms combined with different feature extraction methods. Moreover, it is found that under the feature extraction based on coupled sequence (PseAAC), the classification effect of support vector machine is the best, and it could be combined with ensemble learning to solve the problem of data imbalance. Compared with the existing methods, iSucc-PseAAC has more significance and practicality in predicting lysine succinylation sites.

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.
Animals ; Cell Cycle Proteins/genetics* ; Cell Line ; Cell Survival ; Chondroitin Sulfate Proteoglycans/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Gene Expression Regulation ; Gene Knockdown Techniques ; Infertility, Male ; Male ; Meiosis/genetics* ; Mice ; Mice, Knockout ; Mice, Transgenic ; Phosphate-Binding Proteins/genetics* ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics* ; Rad51 Recombinase/genetics* ; Real-Time Polymerase Chain Reaction ; Spermatocytes/metabolism* ; Spermatogenesis/genetics* ; Spermatogonia/metabolism*

Objective The treatment methods for blood blister-like aneurysm remain controversial due to its special patholog-ical structure,the risk of post-operative rebleeding and the high rate of recurrence. The arm of this paper is to access the feasibility and effectiveness of overlapping stent-assisted coiling in the treatment of blood blister-like aneurysms of the internal carotid artery. Methods Form January 2014 to December 2016,we treated 15 patients with blood blister-like aneurysm of the internal carotid artery by stent-assisted coiling in the Department of Neurosurgery,5 with two Enterprise tents,3 with three Enterprise tents,4 with Enter-prise+LVIS tents,and 3 with two LVIS tents. We determined the rate of immediate embolization of aneurysms by Raymond-Roy Occlu-sion Classification(RROC)and analyzed the clinical characteristics,postoperative complications,and follow-up data. Results All the coils and stents were successfully implanted. RROC showed 9 cases of gradeⅠ(60%),4 cases of gradeⅡ(27%),and 2 cases of gradeⅢimmediate occlusion(13%),with the parent arteries unobstructed in all the cases. Thrombosis in the stent was found in 2 cases intraoperatively,slight stent migration in 1 case,and internal carotid artery dissection in the petrous segment in another,but no cer-ebral vasospasm or aneurysm rupture in any case.Delayed cerebral in-farct was observed in 2 cases postoperatively. The patients were fol-lowed up for 2 weeks to 28 months,which showed that 11 of them were cured,2 remained stable and 2 developed further thrombosis,with an MRS score of 0-2 in 12 cases,4 in 1 case,5 in 1 case, and 6 in 1case. Conclusion Overlapping stent-assisted coiling is effective for the treatment of blood blister-like aneurysm by reduc-ing the risks of rebleeding and recurrence.

As an important herbaceous plant, Scutellaria baicalensis Georgi (Chinese skullcap) is geographically widespread and commonly used throughout the world. In the Chinese medicine market, S. baicalensis has been divided into two primary types, "Ku Qin" (WXR) and "Tiao Qin" (TST). Moreover, TST is also divided into different grades according to the diameter of roots. To explore the distribution patterns of the contents of five biologically activate ingredients (FBAI), we used six-year-old cultivated S. baicalensis and analyzed its growth characteristics as well as the quality difference among different types and diameters in roots. Throughout the entire root, we discovered that contents of the FBAI all initially increased and subsequently decreased from the top to the bottom of the roots. The baicalin content of WXR was less than that of TST. On the contrary, the contents of baicalein, wogonin, and oroxylin A in WXR were up to about two times higher than that in TST. We also found that the 0 to 40 cm part of the S. baicalensis root possessed about 87% of the root biomass and about 92% of the contents of the active ingredients.
Drugs, Chinese Herbal ; chemistry ; Flavanones ; analysis ; Flavonoids ; analysis ; Plant Roots ; chemistry ; Scutellaria baicalensis ; chemistry

Rheum tanguticum from the same area was divided into 8 types of variation according to the plant morphology, content differences of free anthraquinones, combined anthraquinones, double anthrone were studied. The results showed that the functional components of different variation types were significantly different. The average content of free anthraquinone combined anthraquinone was 2.10-6.71 and 15.43-22.04 mg•g⁻¹, respectively. The average content of sennoside A plus sennoside B was 32.88-42.36 mg•g⁻¹. There were significant differences among the difference of 10 kinds of active components, except for sennoside B and physcion glycoside. Interred with the content and proportion of functional components, type B and type E might be potential special medicinal germplasm for diarrhea attack product, type G and type H might be a potential special medicinal germplasm for clearing heat and detoxifing, type C and type F might be potential special medicinal germplasm for activating blood circulation to dissipate blood stasis, type A and type D might be potential special medicinal germplasm with anastaltic funtion. The conclusion laid the foundation for the directional cultivation of fine varieties of special purpose of rhubarb.

OBJECTIVETo investigate the effects of chronic lead exposure on expression of autophagy-associated proteins in rat hippocampus.

METHODSSD rats were randomly divided into three groups: control group was given distilled water, lead-exposed groups were given 0.5 g/L (low-dose) or 2.0 g/L(high-dose) lead acetate solution in drinking water. The rat pups started to drink the lead content water until 60 d maturity. The lead contents in blood and brain samples were analyzed by graphite furnace atomic absorption spectrophotometry. The expressions of Beclin 1, LC3, LAMP2 and cathepsin B proteins were detected by Western blot and immunohistochemistry.

RESULTSCompared with control group, the contents of lead were significantly higher in blood and hippocampus samples in chronic lead-exposed rats (P<0.01). Western blot showed that the expression of Beclin 1 and LC3-II/LC3-I increased significantly in high dose lead-exposed group compared with control group (P<0.05 or P<0.001). The confocal laser immunostaining results demonstrated that increased immunofluorescence staining of cathepsin B in hippocampal neurons compared with control animals.

CONCLUSIONThe disturbance of autophagy-lysosome signaling molecules might be partially contribute to neurotoxicity of chronic lead exposure.

Animals ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; physiology ; Beclin-1 ; Cathepsin B ; metabolism ; Chronic Disease ; Disease Models, Animal ; Female ; Hippocampus ; drug effects ; metabolism ; pathology ; Lead Poisoning ; metabolism ; pathology ; Lysosomal-Associated Membrane Protein 2 ; metabolism ; Male ; Microtubule-Associated Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

In order to search for novel inhibitors of Na+/H+ exchanger isoform-1 (NHE-1), nine feruloylagmatine analogues were designed and synthesized from ferulic acid and agmatine. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and mass spectra, among which compounds 5f-5i were novel compounds. The results of preliminary pharmacological test showed that some of the compounds possessed strong NHE-1 inhibitory activity, among which compounds 5a, 5b and 6c were more potent than cariporide in NHE-1 inhibition.
Agmatine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Cardiotonic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Female ; Male ; Molecular Structure ; Rats ; Rats, Sprague-Dawley ; Sodium-Hydrogen Exchangers ; antagonists & inhibitors ; Structure-Activity Relationship

OBJECTIVETo observe the expressions of the substance P (SP) mRNA and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5 - S2 spinal cord in the rat model of chronic prostatitis pain, and to investigate the changes in the activation of astrocytes and influence of SP on this activation in rat spinal cord astrocytes cultured in vitro.

METHODSThe rat model of chronic prostatitis pain was established by injection of complete Freund's adjuvant (CFA) and assessed by the tail flick threshold test, the control rats injected with sodium chloride and all observed at 0, 14 and 28 days. Changes in the expressions of SP mRNA, NK-1R, glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) in the posterior horn of the L5 - S2 spinal cord were detected by RT-PCR and Western blot. Rat spinal cord astrocytes were cultured in vitro and divided into a control group, cultured with ITS cell culture fluid, and two experiment groups, with Group 1 stimulated with SP at the concentration of 10(-9) - 10(-6) mol/L for 12 hours followed by determination of the expressions of TNF-alpha, IL-1beta, NO and NOS by ELISA and nitrate reductase and colorimetric methods, and Group 2 at 10(-7) mol/L for 0, 24, 48 and 72 hours followed by detection of the GFAP expression by Western blot.

RESULTSThe expressions of SP mRNA, NK-1 R, GFAP, TNF-alpha and iNOS in the posterior horn of the L5 - S2 spinal cord were obviously higher in the rat prostatitis pain models than in the controls, successively higher at 28 than at 14 and 0 d (P < 0.01), and so was the expression of GFAP at 28 than at 14 d in the experiment groups (P < 0.05). SP induced a gradual increase at 10(-7) mol/L in the expression of GFAP in the spinal cord astrocytes at 0 -72 h, significantly different from that of the control group (P < 0.01), and it promoted the excretion of TNF-alpha and IL-1beta and the activity of NO and NOS at 10(-9) - 10(-6) mol/L at 12 h in a concentration-dependent manner, with marked differences between the experiment and control groups (P < 0.01, P < 0.05). But a decreased excretion of IL-1 beta was observed in the 10(-6) mol/L group, though with no significant difference from the control (P > 0.05).

CONCLUSIONChronic prostatitis pain could upregulate the expressions of the excitatory transmitter SP and receptor in the L5 - S2 spinal cord, and result in the activation of astrocytes and increased excretion of proinflammatory cytokines, which may be associated with the persistence and generalization of prostatitis pain.

Animals ; Astrocytes ; metabolism ; Chronic Disease ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Pain ; metabolism ; Prostatitis ; metabolism ; Rats ; Receptors, Neurokinin-1 ; metabolism ; Spinal Cord ; cytology ; metabolism ; pathology ; Substance P ; metabolism

BACKGROUNDMass burn casualties are always a great challenge to a medical team because a large number of seriously injured patients were sent in within a short time. Usually a high mortality is impending. Experiences gained from successful treatment of the victims may be useful in guiding the care of mass casualties in an armed conflict.

METHODSThirty-five burn victims in a single batch, being transferred nonstop by air and highway from a distant province, were admitted 48 hours post-injury. All patients were male with a mean age of (22.4 +/- 8.7) years. The burn extent ranged from 4% to 75% ((13.6 +/- 12.9)%) total body surface area. Among them, thirty-two patients were complicated by moderate and severe inhalation injury, and tracheostomy had been performed in 15 patients. Decompression incisions of burn eschar on extremities were done in 17 cases before transportation. All the thirty-five patients arrived at the destination smoothly via 4-hour airlift and road transportation. Among them, twenty-five patients were in critical condition.

RESULTSThese thirty-five patients were evacuated 6 hours from the scene of the injury, and they were transferred to a local hospital for primary emergency care. The patients were in very poor condition when admitted to our hospital because of the severe injury with delayed and inadequate treatment. Examination of these patients at admission showed that one patient was suffering from sepsis and multiple organ dysfunction syndrome. Dysfunction of the heart, lung, liver, kidney, and coagulation were all found in the patients. Forty-eight operations were performed in the 23 patients during one month together with comprehensive treatment, and the function of various organs was ameliorated after appropriate treatment. All the 35 patients survived.

CONCLUSIONSA well-organized team consisting of several cooperative groups with specified duties is very important. As a whole, the treatment protocol should be individualized, basing on the extent of the injury and the care that the patient had received at the spot. During airlift, the stretchers should be arranged perpendicular to the longitudinal axis of the cabin. The treatment protocol in our hospital consisted mainly of prompt effective relief of all life-threatening complications, followed by early closure of burn wounds, appropriate use of anti-infection therapy, emphasis on nutritional support, correction of metabolic disorders, alleviation of immunosuppression, correction of coagulopathy, and effective support and protection of organ function.

Adolescent ; Adult ; Burns ; drug therapy ; pathology ; surgery ; therapy ; Emergency Medical Services ; Emergency Service, Hospital ; Female ; Hospitals ; Humans ; Male ; Middle Aged ; Time Factors ; Transportation of Patients ; Treatment Outcome ; Young Adult

OBJECTIVETo report the outcome of long bone nonunion of humerus, femur and tibia treated with locking internal fixation and bone graft.

METHODSFrom February 2003 to October 2006, locking internal fixation and bone grafting were employed to treat 5 cases at humerus, 33 cases at femur, 23 cases at tibia. Forty-four of the patients were men, and 17 were women. The mean age was 38 years (range 7-70 years). The nonunion had resulted from failure of internal fixation in 47 cases, failure of external fixation in 5 cases, infection in 9 cases. The history of nonunion lasted from 10 to 156 months (mean 19 months). There were 42 patients treated with locking compression plate (LCP), and 19 patients with less invasive stabilization system (LISS). For bone grafting, autogenous ilium was used in 55 patients, autogenous ilium and allograft bone was used in 3 patients, allograft bone and Wright DBM artificial bone was used in 3 patients.

RESULTSAll the 61 patients were followed up for an average 12 months (range 6-24 months) only to reveal solid bone union in all the fracture, with a mean healing time of 4.8 months (ranged from 4 to 6 months). No loosening or breakage of the implants occurred in this series. The Knee Society Scores (KSS) was used to evaluate knee function in 47 patients with peri-knee joint nonunion, excellent result were seen in 35 patients, good in 7 patients, fare in 1 patients, poor in 4 patients.

CONCLUSIONLocking internal fixation can be used to treat effectively bone nonunion at the humerus, femur and tibia.

Adolescent ; Adult ; Aged ; Bone Plates ; Child ; Female ; Femoral Fractures ; surgery ; Follow-Up Studies ; Fracture Fixation, Internal ; methods ; Fractures, Ununited ; surgery ; Humans ; Humeral Fractures ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Tibial Fractures ; surgery ; Treatment Outcome