Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection for circumferential mixed hemorrhoids

AIM:To identify a more effective treatment protocol for circumferential mixed hemorrhoids.METHODS:A total of 192 patients with circumferential mixed hemorrhoids were randomized into the treatment group,where they underwent Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection,or the control group,where traditional external dissection and internal ligation were performed.Postoperative recovery and complications were monitored.RESULTS:The time to wound healing was 12.96 ± 2.25 d in the treatment group shorter than 19.58 ± 2.71 d in the control group.Slight pain rate was 58.3% in the treatment group higher than 22.9% in the control group;moderate pain rate was 33.3% in the treatment group lower than 56.3% in the control group severe pain rate was 8.4% in the treatment group lower than 20.8% in the control group.No edema rate was 70.8% in the treatment group higher than 43.8% in the control group;mild local edema rate was 26% in the treatment group lower than 39.6% in the control group obvious local edema was 3.03% in the treatment group lower than 16.7% in the control group.No stenosis rate was 85.4% in the treatment group higher than 63.5% in the control group;moderate stenosis rate was 14.6% in the treatment group Lower than 27.1% in the control group severe anal stenosis rate was 0% in the treatment group lower than 9.4% in the control group.CONCLUSION:Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection is the optimal treatment for circumferential mixed hemorrhoids and can be widely applied in clinical settings.

Local injection of bone morphogenetic protein 7 promotes neuronal regeneration and motor function recovery after acute spinal cord injury

After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether direct injection of BMP7 into acutely injured ratalalo createrywith 50 ng BMP7（BMP7 group）or physiological saline（control group）for 7 consecutive days.Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials（MEP）decreased after spinal cord injury.At 8 weeks post-operation,the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group.Basso,Beattie,Bresnahan scale（BBB）scores,hematoxylin-eosin staining,and western blot assay showed that at 1,2,4 and 8 weeks post-operation,BBB scores were increased;Nissl body staining was stronger;the number of Nissl-stained bodies was increased;the number of vacuoles gradually decreased;the number of synapses was increased;and the expression of neuronal marker,neurofilament protein 200,was increased in the hind limbs of the BMP7 group compared with the control group.Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups.These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint(TMJ) osteoarthritis(OA);however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4(Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore,Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Therapeutic effect of minimally invasive intracranial hematoma evacuation in the treatment of hypertensive cerebral hemorrhage and TCD evaluation

Objective:To explore the therapeutic effect of minimally invasive intracranial hematoma evacuation in the treatment of hypertensive cerebral hemorrhage and the value of dynamic TCD monitoring in predicting the neurological function recovery.Methods: A total of 70 patients with hypertensive cerebral hemorrhage who were admitted in our hospital were included in the study and divided into the minimally invasive group and conservative group with 35 cases in each group according to different treatment protocols. The patients in the two groups were given drug conservative treatments. On this basis, the patients in the minimally invasive group were given urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle. TCD was performed before treatment, 1 d, 5 d, 10 d, and 21 d after treatment. The hematoma and edema volume was calculated. NIHSS was used to evaluate the neurological function recovery.Results: Vs, Vd, and Vm after treatment in the minimally invasive group were significantly elevated, while PI was significantly reduced. Vs, Vd, and Vm after treatment in the conservative group were reduced first and elevated later, while PI was elevated first and reduced later, and reached the lowest/peak 10d after treatment. Vs, Vd, and Vm 5 d, 10 d, and 21 d after treatment in the minimally invasive group were significantly higher than those in the conservative group, while PI was significantly lower than that in the conservative group. The hematoma and edema volume after treatment in the two groups was significantly reduced. The hematoma and edema volume at each timing point was significantly lower than that in the conservative group. NIHSS score after treatment in the minimally invasive group was significantly reduced. NIHSS score in the conservative group was elevated first and reduced later, reached the peak 10d after treatment, and at each timing point was higher than that in the minimally invasive group.Conclusions:The early minimally invasive operation can significantly improve the hematoma adjacent blood flow volume in patients with hypertensive cerebral hemorrhage, and contribute to the neurological function recovery. TCD not only can be applied in the dynamic monitoring of cerebral blood flow volume in patients with hypertensive cerebral hemorrhage, but also has a certain value in evaluating the prognosis of neurological function.

The impact of nurses’organizational commitment on their perceptions of the work environment:Strong mediating effect of the psychological contract

Objective:The objective is to assess the direct and indirect effects of nurses’organizational commitment(OC)on their work environment perceptions(WEP)and the role of the psychological contr act(PC).Methods:A cross‑sectional quantitative study of 3047 registered nurses in four Chinese hospitals was conducted.The Essentials of Magnetism II(Chinese version),OC,and PC scales were used in the study,and the structural equation modeling was used to assess the connections among variables.Results:The results showed that OC was positively correlated with WEP(r=0.561,P<0.001),and PC was negatively correlated with the WEP(r=−0.717,P<0.001),and OC(r=−0.739,P<0.001).Nurses’PC played a strong mediating role between OC and WEP,accounting for 87.64%of the total effect.Besides,PC played an important role in creating a healthy work environment.Conclusions:The exploration of the relationships among WEP,PC,and OC provides new insights for hospital managers to build a better work environment for nurses,which is conducive to maintaining a stable nurse team and providing high‑quality nursing services for patients.

Protective effects of umbilical cord mesenchymal stem cell exosomes in a diabetic rat model through live retinal imaging

AIM:To assess the protective effect of human umbilical cord mesenchymal stem cell exosomes(hucMSC-Exs)in a diabetic rat model by using a variety of retinal bioassays.METHODS:hucMSCs were subjected to differential ultracentrifugation for the collection of exosomes,and transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA)using a NanoSight analysis system and Western blotting(WB)were used to analyze the expression of surface marker proteins such as CD63,CD9 and Calnexin.Streptozotocin(STZ)was injected into the intraperitoneal cavity to establish a diabetic model.Rats were divided into a normal group,diabetic group and hucMSC-Ex group.Fundus fluorescein angiography(FFA),optical coherence tomography(OCT)and other live imaging methods were used to observe the fundus of the rats.Finally,the eyeballs of rats from each group were collected for hematoxylin-eosin(HE)staining to further analyze the retinal structure.RESULTS:Through TEM,NTA and WB,we successfully isolated hucMSC-Exs.Subsequent FFA and OCT confirmed that hucMSC-Exs effectively prevented early retinal vascular damage and thickening of the retina.Finally,HE staining of rat retinal sections revealed that exosomes effectively alleviated retinal structure disruption caused by diabetes.CONCLUSION:hucMSC-Exs have a protective effect on the retina in diabetic rat through FFA,OCT and HE staining.

Protective effect of human umbilical cord mesenchymal stem cell-derived exosomes on rat retinal neurons in hyperglycemia through the brain-derived neurotrophic factor/TrkB pathway

AIM:To explore whether human umbilical cord mesenchymal stem cell(hUCMSC)-derived exosomes(hUCMSC-Exos)protect rat retinal neurons in high-glucose(HG)conditions by activating the brain-derived neurotrophic factor(BDNF)-Trk B pathway.METHODS:h UCMSC-Exos were collected with differential ultracentrifugation methods and observed by transmission electron microscopy.Enzyme-linked immunosorbent assays(ELISAs)was used to quantify BDNF in hUCMSC-Exos,and Western blot was used to identify surface markers of hUCMSC-Exos.Rat retinal neurons were divided into 4 groups.Furthermore,cell viability,cell apoptosis,and TrkB protein expression were measured in retinal neurons.RESULTS:hUCMSCs and isolated hUCMSC-Exos were successfully cultured.All hUCMSC-Exos showed a diameter of 30 to 150 nm and had a phospholipid bimolecular membrane structure,as observed by transmission electron microscopy.ELISA showed the BDNF concentration of hUCMSCs-Exos was 2483.16±281.75.hUCMSCs-Exos effectively reduced the apoptosis of retinal neuron rate and improved neuron survival rate,meanwhile,the results of immunofluorescence verified the fluorescence intensity of TrKB in neurons increased.And all above effects were reduced by treated hUCMSCs-Exos with BDNF inhibitors.hUCMSC-Exos effectively reduced the apoptosis rate of retinal neurons by activating the BDNF-TrkB pathway in a HG environment.CONCLUSION:In the HG environment,hUCMSC-Exos could carry BDNF into rat retinal neurons,inhibiting neuronal apoptosis by activating the BDNF-TrkB pathway.

Mesenchymal stem cell-derived exosomes inhibit the VEGF-A expression in human retinal vascular endothelial cells induced by high glucose

AIM:To determine the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells(hUCMSCs)on the expression of vascular endothelial growth factor A(VEGF-A)in human retinal vascular endothelial cells(HRECs).METHODS:Exosomes were isolated from hUCMSCs using cryogenic ultracentrifugation and characterized by transmission electron microscopy,Western blotting and nanoparticle tracking analysis.HRECs were randomly divided into a normal control group(group A),a high glucose model group(group B),a high glucose group with 25μg/mL(group C),50μg/mL(group D),and 100μg/mL exosomes(group E).Twenty-four hours after coculture,the cell proliferation rate was detected using flow cytometry,and the VEGF-A level was detected using immunofluorescence.After coculture 8,16,and 24h,the expression levels of VEGF-A in each group were detected using PCR and Western blots.RESULTS:The characteristic morphology(membrane structured vesicles)and size(diameter between 50 and 200 nm)were observed under transmission electron microscopy.The average diameter of 122.7 nm was discovered by nanoparticle tracking analysis(NTA).The exosomal markers CD9,CD63,and HSP70 were strongly detected.The proliferation rate of the cells in group B increased after 24h of coculture.Immunofluorescence analyses revealed that the upregulation of VEGF-A expression in HRECs stimulated by high glucose could be downregulated by cocultured hUCMSC-derived exosomes(F=39.03,P<0.01).The upregulation of VEGF-A protein(group C:F=7.96;group D:F=17.29;group E:F=11.89;8h:F=9.45;16h:F=12.86;24h:F=42.28,P<0.05)and mRNA(group C:F=4.137;group D:F=13.64;group E:F=22.19;8h:F=7.253;16h:F=16.98;24h:F=22.62,P<0.05)in HRECs stimulated by high glucose was downregulated by cocultured hUCMSC-derived exosomes(P<0.05).CONCLUSION:hUCMSC-derived exosomes downregulate VEGF-A expression in HRECs stimulated by high glucose in time and concentration dependent manner.

Melanin nanoparticles alleviate sepsis-induced myocardial injury by suppressing ferroptosis and inflammation

Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a critical role in the development of heart diseases.Therefore,we hypothesized that anti-ferroptosis agent might be a novel potential therapeutic strategy for sepsis-induced cardiac injury.Herein,we demonstrated that a small biocompatible and MRI-visible melanin nanoparticles(MMPP)improves myocardial function by inhibiting ROS-related ferroptosis signaling pathway.In LPS-induced murine sepsis model,after a single dose intravenously injection of MMPP treatment,MMPP markedly alleviated the myocardial injury including cardiac function and heart structure disorder through suppressing iron-accumulation induced ferroptosis.In vitro,MMPP inhibited cardiomyocyte death by attenuating oxidative stress,inflammation and maintaining mitochondrial homeostasis.Collectively,our findings demonstrated that MMPP protected heart against sepsis-induced myocardial injury via inhibiting ferroptosis and inflammation,which might be a novel therapeutic approach in future.

Manganese nanodepot augments host immune response against coronavirus

Interferon(IFN)responses are central to host defense against coronavirus and other virus infections.Manganese(Mn)is capable of inducing IFN production,but its applications are limited by nonspecific distributions and neurotoxicity.Here,we exploit chemical engineering strategy to fabricate a nanodepot of manganese(nanoMn)based on Mn2+.Compared with free Mn2+,nanoMn enhances cellular uptake and persistent release of Mn2+in a pH-sensitive manner,thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo.Preferentially phagocytosed by macrophages,nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci,eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage.Besides,nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation,suggesting its potential as a vaccine adjuvant.Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese.Therefore,nanoMn offers a simple,safe,and robust nanoparticle-based strategy against coronavirus.