Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

The aim of the present study was to investigate the effect of lipoxin A4 (LXA4)pretreatment on cognitive function of aged rats after global cerebral ischemia reperfusion,and to explore its possible mechanism.Thirty-six aged male Sprague-Dawley rats were randomly divided into three groups (n=12 each):sham-operation group (S group),global cerebral ischemia reperfusion group (I/R group) and LXA4-pretreatment group (L group).The rat model of global cerebral ischemia reperfusion was established by occlusion of the bilateral common carotid artery with hypotension.The cognitive function of rats was determined by a step-down type passive avoidance test and Morris Water Maze test on the third day after reperfusion.Rats were sacrificed after Water Maze test and the pathological changes ofhippocampal CA1 region were observed and the related inflammatory mediators were determined.As compared with S group,the escape latency in I/R group was prolonged from the first day to the fifth day,while that in L group was prolonged from the first day to the third day.The retention time in I/R group and L group in the first quadrant was shortened.The reaction time,frequency of reaction mistake and frequency of escape mistake in I/R group increased,and the latent period shortened.The frequency of escape mistake in L group increased,and the damage in the hippocampal CA1 region of I/R group and L group was obvious.The levels of S-100β,TNF-α,IL-lβ,IL-10 and NF-κB in I/R group and L group increased.As compared with I/R group,the escape latency in L group was shortened from the first day to the fifth day,and the retention time in the first quadrant prolonged.The reaction time,frequency of reaction mistake and frequency of escape mistake in L group decreased,and the latent period prolonged.The damage in the hippocampal CA1 region of L group was alleviated as well.The levels of S-100β,TNF-α,IL-1β and NF-κB in L group decreased,and those of IL-10 increased.It can be concluded that LXA4 pretreatment can improve the cognitive function in aged rats after global cerebral ischemia reperfusion probably by inhibiting the inflammatory reaction.

OBJECTIVETo summarize clinical application results of repair soft tissue defect in forefoot with a reversed lateral soleus muscle flap on peroneal artery pedicle.

METHODSFrom January 2005 to January 2013, 8 patients with soft-tissue defect on forefoot were underwent reconstruction with a reversed lateral soleus muscle flap on peroneal artery pedicle. There were 6 males and 2 female, aged from 16 to 48 years with an average of 26.8 years old. The reversed lateral soleus muscle flap was transposed to the forefoot defect area, then immediate coverage of the muscle flaps were performed by a meshed split-thickness free skin graft. The donor site was closed directly. The muscle flap survey was observed after the repair of the forefoot.

RESULTSAll muscle flaps had survived completely. No clinical vascular deficiency was found on muscle flaps postoperatively. One case occurred recipient area sustained insignificant superficial infection, one patient developed distal muscle flap small skin graft necrosis, and spontaneous heal by 2 weeks' change dressing. Follow-up period was ranged form 2.5 to 5.5 years with an average of 3.5 years postoperatively. A good contour was confirmed at the recipient area. According to Cedell questionnaire, 6 patients obtained good results and 2 fair.

CONCLUSIONSWhen the local skin flap or muscle flap application is limited, lateral soleus muscle flap survey is satisfactory after repair and very suitable for repair of soft tissue defect of forefoot.

Curcumin, the medically active component from Curcuma longa (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein-protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation.

OBJECTIVETo investigate the risk factors of surgical site infection (SSI) in definitive surgery of intestinal fistulas.

METHODSPatients with gastrointestinal fistula undergoing definitive operation during November 2011 to November 2013 in Jinling Hospital were prospectively enrolled in the study. Risk factors of SSI were analyzed. Patients' characteristics, surgery-related data and fistula-related data were prospectively collected. Risk factors of SSI were analyzed.

RESULTSA total of 191 cases were enrolled and 51 cases developed SSI. Univariate analysis showed that patients with risk index category (RIC)≥2, length of abdominal incisions>15 cm, and duration of drainage tubes>10 days had significantly higher incidence of SSI (P<0.05). Multivariate Logistics analysis demonstrated that RIC and duration of drainage tube were independent risk factors for SSI (P=0.02, P=0.01, respectively).

CONCLUSIONSRIC≥2 and duration of drainage tubes>10 days are independent risk factors for development of SSI.

Humans ; Incidence ; Intestinal Fistula ; Multivariate Analysis ; Risk Factors ; Surgical Wound Infection

OBJECTIVETo report the clinical application results of free deep inferior epigastric perforator flap in the repair of soft tissue defect.

METHODSFrom January 2006 to January 2012,13 patients with soft tissue defect (7 cases in leg and 6 cases in forearm) underwent reconstruction with a free deep inferior epigastric perforator flap. There were 9 males and 4 females, aged from 21 to 45 years old with an average of 33 years. Soft tissue defect in the extremities were from 7 cm x 17 cm to 8 cm x 26 cm. The medial branch and lateral brangh flaps were 7 cases and 6 cases respectively. The donor site was closed directly.

RESULTSOne patient developed small wound dehiscence, which spontaneous healed at one month after surgery. All the flaps had survived completely. Follow-up period ranged from 1.8 to 4.0 years with the mean of 2.8 years postoperatively. Satisfactory clinical results were obtained in 12 cases. A good contour was confirmed at the recipient area.

CONCLUSIONThe free deep inferior epigastric perforator flap for the extremities defects of soft tissue is a good option. This technique is safe and reliable, and can decrease the injury of donor site.

Adult ; Extremities ; surgery ; Female ; Humans ; Male ; Middle Aged ; Perforator Flap ; Soft Tissue Injuries ; surgery

Objective:To report the clinical application results of free deep inferior epigastric perforator flap in the repair of soft tissue defect. Methods:From January 2006 to January 2012,13 patients with soft tissue defect(7 cases in leg and 6 cas-es in forearm) underwent reconstruction with a free deep inferior epigastric perforator flap. There were 9 males and 4 females , aged from 21 to 45 years old with an average of 33 years. Soft tissue defect in the extremities were from 7 cm×17 cm to 8 cm×26 cm. The medial branch and lateral brangh flaps were 7 cases and 6 cases respectively. The donor site was closed directly. Re-sults:One patient developed small wound dehiscence ,which spontaneous healed at one month after surgery. All the flaps had survived completely. Follow up period ranged from 1.8 to 4.0 years with the mean of 2.8 years postoperatively. Satisfactory clinical results were obtained in 12 cases. A good contour was confirmed at the recipient area. Conclusion:The free deep infe-rior epigastric perforator flap for the extremities defects of soft tissue is a good option. This technique is safe and reliable ,and can decrease the injury of donor site.

OBJECTIVETo summarize clinical outcomes of using medial transposition of the radial nerve in humeral shaft fracture fixation.

METHODSFrom January 2005 to December 2009, 16 patients with humeral shaft fractures were treated with medial transposition of the radial nerve during open reduction and anterolateral plate fixation, included 12 males and 4 females ranging in age from 26 to 49 years, with a mean of 36 years. There were 7 fractures in the right and 9 in the left. According to AO classification, 6 fractures were type A3.2, 5 fractures were type A2.2, 2 fractures were type A1.2 and 3 fractures were type B2.2. The results were evaluated with DASH (disability of arm-shoulder-hand) Questionnaire by the American Academy of Orthopedic Surgeons (AAOS), where 0 indicates normal upper extremity function, and 1 to 100 indicate varying degrees of damage to the function of the upper extremities.

RESULTSThere was no neurologic complication or postoperative would infection in this series. The followed-up period ranged from 20 to 46 (means 29) months postoperatively. The clinical outcomes were evaluated with DASH Questionnaire, indicating that all patients reached a normal value (value of 0). The function of the upper extremities recovered satisfactorily. There was no surgery-related complication.

CONCLUSIONMedial transposition of the radial nerve is safe and does not cause iatrogenic nerve injury. It protects the radial nerve during open reduction and anterolateral plate fixation of humeral shaft fractures.

Adult ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Humeral Fractures ; surgery ; Male ; Middle Aged ; Radial Nerve ; surgery

OBJECTIVETo investigate the change of T lymphocyte subsets, interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha in the tumor- bearing mice and patients with oral cancer receiving thermo-chemotherapy, and investigate the correlation among them.

METHODSAfter treatments, the expression of lymphocyte transformation index (LTI), IL-2 and TNF-alpha in the tumor-bearing mice were detected with methyl thiazolyl tetrazolium (MTT), the expression of IL-2 and TNF-alpha in the patients with oral cancer were detected with MTT, the expression of LTI, CD4+ and CD8+ were detected with 3H-TdR incorporation.

RESULTSLTI, IL-2 and TNF-alpha of thermo-chemotherapy group (HP group) had no significant difference comparing with those of normal mice group (N group) (P>0.05), but which were significantly higher than those of chemotherapy group (P group) and no treatment group (NT group) (P<0.01). In clinical trials, the expression of LTI, CD4+, CD4+/CD8+, IL-2 and TNF-alpha on oral cancer patients after thermo-chemotherapy were significantly higher than those before thermo-chemotherapy (P<0.01).

CONCLUSIONAfter thermo-chemotherapy, the expression of LTI, IL-2 and TNF-alpha of tumor-bearing hosts are significantly improved, there is a significant correlation between IL-2 and T cell.

Animals ; Humans ; Interleukin-2 ; Mice ; Mouth Neoplasms ; Neoplasms ; T-Lymphocyte Subsets ; Tumor Necrosis Factor-alpha

Arylalkylamine N-acetyltransferase (AANAT) and Hydroxyindole O-methyltransferase(HIOMT) are the key regulation enzymes in the melatonin biosynthesis pathway in mammals. The AANAT and HIOMT genes were constructed into a binary plant expression vector YXu55. Using leaf strips as the recipiences, we efficiently transformed tobacco (Nicotiana tabacum) variety qinyan 95 by the Agrobacterium mediated method. After gradient selection with gentamycin, a number of transgenic plants were regenerated. Southern blot and RT-PCR analyses showed that the AANAT-HIOMT genes were integrated into the genome of the transgenic plants and the target genes could express at the level of RNA transcription. By RP-HPLC, we measured the melatonin contents in transgenic plants. The results showed that the melatonin level in YXu55 (containing the gentamycin-resistance gene, the AANAT gene and HIOMT gene) transgenic plants were much higher than those in pZP122 (control containing only the gentamycin-resistance gene) transgenic plants and nontransgenic plants. The content of melatonin in pZP122 transgenic plants was nearly the same as that in nontransgenic plants. Physiological determination of antioxidative characteristics demonstrated that 1) the capacity of total antioxidation, 2) the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) and 3) the content of glutathione (GSH) were increased in YXu55 transgenic plants containing the AANAT-HIOMT genes as compared to the control plants (pZP122 or nontransgenic plants). At the same time, malonaldehyde (MDA) content did not appear remarkably difference between transgenic plants and nontransgenic plants. The above mentioned facts indicate enhancement of melatonin levels in YXu55 transgenic plants might help to reduce damage by oxidative stress.
Acetylserotonin O-Methyltransferase ; genetics ; Agrobacterium tumefaciens ; genetics ; Arylalkylamine N-Acetyltransferase ; genetics ; Catalase ; metabolism ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; Melatonin ; biosynthesis ; Peroxidase ; metabolism ; Plants, Genetically Modified ; enzymology ; genetics ; Superoxide Dismutase ; metabolism ; Tobacco ; enzymology ; genetics ; Transduction, Genetic ; methods