The fate and prospects of stem cell therapy in the treatment of hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of long-term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI-induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE).

Analgesic Effects and Adverse Reactions of Lidocaine for Patient-Controlled Intravenous Analgesia on Patients Undergoing Open Hepatectomy: A Retrospective Analysis.

PURPOSE: The aim of this study was to investigate the effect of lidocaine for patient controlled intravenous analgesia (PCIA) in patients who underwent open hepatectomy. DESIGN: A retrospective analysis. METHODS: A total of 281 patients who underwent open hepatectomy from July 2018 to December 2018 were included. All patients were assigned into two groups: the lidocaine group (PCIA consisted of lidocaine, sufentanil, tramadol and granisetron) and the control group (PCIA consisted of sufentanil, tramadol and granisetron). The postoperative visual analogue scale (VAS) and complications (including respiratory depression, hypotension, nausea and vomiting, pruritus, numbness of the corners of the mouth, dizziness) between the groups were compared. FINDINGS: There were no significant differences between the characteristics, duration of surgery and anesthesia, and recovery of postoperative activity between the two groups. In the first 3 days after the operation, the postoperative VAS score of the lidocaine group was lower than that of the control group at resting state, while after activity, the postoperative VAS contrast results were completely opposite. In particularly, the resting state at 48 hours (h) (1.05 ± 1.25 vs 1.57 ± 1.54) after surgery and the activity state at 72 h (3.02 ± 1.51 vs 2.2 ± 1.66) after surgery (P < 0.05). The incidence of mouth numbness and dizziness were significantly increased in the lidocaine group (P < 0.05). CONCLUSION: The addition of lidocaine in PCIA was not beneficial to improve the pain during activities and increased the incidence of perioral numbness and dizziness.

P75 neurotrophin receptor as a therapeutic target for drug development to treat neurological diseases.

The interaction of neurotrophins with their receptors is involved in the pathogenesis and progression of various neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury and acute and chronic cerebral damage. The p75 neurotrophin receptor (p75NTR) plays a pivotal role in the development of neurological dysfunctions as a result of its high expression, abnormal processing and signalling. Therefore, p75NTR represents as a vital therapeutic target for the treatment of neurodegeneration, neuropsychiatric disorders and cerebrovascular insufficiency. This review summarizes the current research progress on the p75NTR signalling in neurological deficits. We also summarize the present therapeutic approaches by genetically and pharmacologically targeting p75NTR for the attenuation of pathological changes. Based on the evolving knowledge, the role of p75NTR in the regulation of tau hyperphosphorylation, Aß metabolism, the degeneration of motor neurons and dopaminergic neurons has been discussed. Its position as a biomarker to evaluate the severity of diseases and as a druggable target for drug development has also been elucidated. Several prototype small molecule compounds were introduced to be crucial in neuronal survival and functional recovery via targeting p75NTR. These small molecule compounds represent desirable agents in attenuating neurodegeneration and cell death as they abolish activation-induced neurotoxicity of neurotrophins via modulating p75NTR signalling. More comprehensive and in-depth investigations on p75NTR-based drug development are required to shed light on effective treatment of numerous neurological disorders.

Patients with gastroenteric tumor after upper abdominal surgery were more likely to require rescue analgesia than lower abdominal surgery.

OBJECTIVES: To find out the reasons why patients still need to use rescue analgesics frequently after gastrointestinal tumor surgery under the patient-controlled intravenous analgesia (IV-PCA), and the different abdominal surgery patients using the difference of analgesics. METHODS: A total of 970 patients underwent abdominal operation for gastrointestinal tumors were included. According whether patients used dezocine frequently for rescue analgesics within 2 days after surgery, they assigned into two groups: RAN group (Patients who did not frequently use rescue analgesia, 406 cases) and RAY group (Patients who frequently used rescue analgesia, 564 cases). The data collected included patient's characteristics, postoperative visual analogue scale (VAS), nausea and vomiting (PONV), and postoperative activity recovery time. RESULTS: No differences were observed in the baseline characteristics. Compared with the RAN group, patients in the RAY group had a higher proportion of open surgery, upper abdominal surgery, VAS score at rest on the first 2 days after surgery and PONV, and a slower recovery of most postoperative activities. Under the current use of IV-PCA background, the proportion of rescue analgesics used by patients undergoing laparotomy and upper abdominal surgery was as high as 64.33% and 72.8%, respectively. Regression analysis showed that open surgery (vs laparoscopic surgery: OR: 2.288, 95% CI: 1.650-3.172) and the location of the tumor in the upper abdomen (vs lower abdominal tumor: OR: 2.738, 95% CI: 2.034-3.686) were influential factors for frequent salvage administration. CONCLUSIONS: In our patient population, with our IV-PCA prescription for postoperative pain control, patient who underwent open upper abdominal surgery required more rescue postoperative analgesia.

Analgesic effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine after open gastrointestinal tumor surgery: a retrospective study.

BACKGROUND: To investigated the effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine for patient-controlled intravenous analgesia (PCIA) on patients after open gastrointestinal tumor surgery, and compared this combination with traditional PCIA with pure opioids or epidural analgesia (PCEA). METHODS: Patients (n = 640) who underwent open gastrointestinal tumor surgery and received patient-controlled analgesia (PCA) were included. According to the type of PCA, patients were assigned to three groups: MPCIA (PCIA with sufentanil, flurbiprofen axetil, dexmedetomidine and metoclopramide), OPCIA (PCIA with sufentanil, tramadol and metoclopramide) and PCEA group (PCEA with sufentanil and ropivacaine). The characteristics of patients, intraoperative use of analgesics, postoperative visual analogue scale (VAS), postoperative adverse reactions and postoperative recovery were collected. The primary outcome was postoperative VAS score. One-way ANOVA, Kruskal-Wallis H test, Fisher exact probability method, and binary logistic regression analysis were used for analysis. RESULTS: There were no significant differences in the characteristics of patients, operation time, tumor site and the use of postoperative rescue analgesics among the groups. In the first two days after open gastrointestinal tumor surgery, the VAS (expressed by median and interquartile range) of MPCIA (24th h, resting: 1,1; movement: 3,2. 48th h, resting: 0,1; movement: 2,1.) and PCEA (24th h, resting: 0,1; movement: 2,1. 48th h, resting: 0,1; movement: 2,2.) groups were significantly lower than those of OPCIA group (24th h, resting: 2.5,2; movement: 4,2. 48th h, resting: 1.5,1.75; movement: 3,1.) (all p <  0.01). The incidence of postoperative nausea and vomiting in MPCIA group was 13.6% on the first day after surgery, which was significantly higher than that in PCEA group. There was no significant difference in the incidence of other postoperative adverse events. Higher intraoperative sufentanil dosage (OR (95%CI) = 1.017 (1.002-1.031), p = 0.021), lower body mass index (OR (95%CI) = 2.081 (1.059-4.089), p = 0.033), and tumor location above duodenum (OR (95%CI) = 2.280 (1.445-3.596), p <  0.001) were associated with poor postoperative analgesia. CONCLUSIONS: The analgesic effects of PCIA with sufentanil in combination with flurbiprofen axetil and dexmedetomidine on postoperative analgesia was better than that of traditional pure opioids PCIA, and similar with that of PCEA.

Panax notoginseng saponin attenuates the hypoxic-ischaemic injury in neonatal rats by regulating the expression of neurotrophin factors.

Neonatal hypoxic-ischaemic (HI) injury is a serious complication of neonatal asphyxia and the leading cause of neonatal acute death and chronic neurological injury, and the effective therapeutic method is lacking to improve patients' outcomes. We reported in this study that panax notoginseng saponin (PNS) may provide a treatment option for HI. HI model was established using neonatal Sprague-Dawley rats and then intraperitoneally injected with different dosage of PNS, once a day for 7 days. Histological staining and behavioural evaluations were performed to elucidate the pathological changes and neurobehavioural variation after PNS treatment. We found PNS administration significantly reduced the infarct volume of brain tissues and improved the autonomous activities of neonatal rats, especially with higher dosage. PNS treatment at 40 mg/kg reduced neuronal damage, suppressed neuronal apoptosis and depressed astroglial reactive response. Moreover, the long-term cognitive and motor functions were also improved after PNS treatment at 40 mg/kg. Importantly, PNS treatment elevated the levels of BDNF and TrkB but decreased the expression of p75NTR both in the cortex and hippocampus of HI rats. The therapeutic efficacy of PNS might be correlated with PNS-activated BDNF/TrkB signalling and inactivation of p75NTR expression, providing a novel potential therapy for alleviating HI injury.

The efficacy of ultrasound-guided stellate ganglion block in alleviating postoperative pain and ventricular arrhythmias and its application prospects.

Stellate ganglion block (SGB) has been applied in clinic for almost a century as a therapeutic procedure to alleviate pain-related syndromes and vascular deficits in the upper extremities. A great number of causative side effects and complications due to technological insufficiency and anatomical variations called for the popularity of ultrasound-guided SGB which has made tremendous contribution for clinical diagnosis and therapy, primarily in postoperative pain and cardiac and vascular disorders. This work was aimed at systematically summarizing the current clinical application of ultrasound-guided SGB and putting forward the potential prospective application in future. By searching ultrasound-guided SGB-related works on PubMed database, we mainly elucidated the analgesic effect of preoperative SGB in patients undergoing surgical procedures and substantial reduction in patients with ventricular arrhythmias. The volume of local anesthetics used in ultrasound-guided SGB has been diminished in the recent few years' investigations and successful operation of ultrasound-guided SGB could be achieved with minimal safe volume of local anesthetics. This invasive and safe procedure shows vast potential for future development in clinical treatment for autonomic nervous system and autoimmune disorders. We also put forward hypothesis that ultrasound-guided SGB could be applied combined with controlled hypotension to reduce the intraoperative complications in orthopedic surgery such as insufficiency of cerebral blood flow and reflexive tachycardia. Thus, it is of vital essence to improve the professional skills of physicians for the high rate of success and explore more effective measures which could enhance therapeutic effects when combined with ultrasound-guided SGB in alleviating misery of patients.

Complexin I knockout rats exhibit a complex neurobehavioral phenotype including profound ataxia and marked deficits in lifespan.

Complexin I (CPLX1), a presynaptic small molecule protein, forms SNARE complex in the central nervous system involved in the anchoring, pre-excitation, and fusion of axonal end vesicles. Abnormal expression of CPLX1 occurs in several neurodegenerative and psychiatric disorders that exhibit disrupted neurobehaviors. CPLX1 gene knockout induces severe ataxia and social behavioral deficits in mice, which has been poorly demonstrated. Here, to address the limitations of single-species models and to provide translational insights relevant to human diseases, we used CPLX1 knockout rats to further explore the function of the CPLX1 gene. The CRISPR/Cas9 gene editing system was adopted to generate CPLX1 knockout rats (CPLX1-/-). Then, we characterized the survival rate and behavioral phenotype of CPLX1-/- rats using behavioral analysis. To further explain this phenomenon, we performed blood glucose testing, Nissl staining, hematoxylin-eosin staining, and Golgi staining. We found that CPLX1-/- rats showed profound ataxia, dystonia, movement and exploratory deficits, and increased anxiety and sensory deficits but had normal cognitive function. Nevertheless, CPLX1-/- rats could swim without training. The abnormal histomorphology of the stomach and intestine were related to decreased weight and early death in these rats. Decreased dendritic branching was also found in spinal motor neurons in CPLX1-/- rats. In conclusion, CPLX1 gene knockout induced the abnormal histomorphology of the stomach and intestine and decreased dendritic branching in spinal motor neurons, causing different phenotypes between CPLX1-/- rats and mice, even though both of these phenotypes showed profound ataxia. These findings provide a new perspective for understanding the role of CPLX1.

COX5A over-expression protects cortical neurons from hypoxic ischemic injury in neonatal rats associated with TPI up-regulation.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) represents as a major cause of neonatal morbidity and mortality. However, the underlying molecular mechanisms in brain damage are still not fully elucidated. This study was conducted to determine the specific potential molecular mechanism in the hypoxic-ischemic induced cerebral injury. METHODS: Here, hypoxic-ischemic (HI) animal models were established and primary cortical neurons were subjected to oxygen-glucose deprivation (OGD) to mimic HIE model in vivo and in vitro. The HI-induced neurological injury was evaluated by Zea-longa scores, Triphenyte-trazoliumchloride (TTC) staining the Terminal Deoxynucleotidyl Transferased Utp Nick End Labeling (TUNEL) and immunofluorescent staining. Then the expression of Cytochrome c oxidase subunit 5a (COX5A) was determined by immunohistochemistry, western blotting (WB) and quantitative real time Polymerase Chain Reaction (qRT-PCR) techniques. Moreover, HSV-mediated COX5A over-expression virus was transducted into OGD neurons to explore the role of COX5A in vitro, and the underlying mechanism was predicted by GeneMANIA, then verified by WB and qRT-PCR. RESULTS: HI induced a severe neurological dysfunction, brain infarction, and cell apoptosis as well as obvious neuron loss in neonatal rats, in corresponding to the decrease on the expression of COX5A in both sides of the brain. What's more, COX5A over-expression significantly promoted the neuronal survival, reduced the apoptosis rate, and markedly increased the neurites length after OGD. Moreover, Triosephosephate isomerase (TPI) was predicted as physical interactions with COX5A, and COX5A over-expression largely increased the expressional level of TPI. CONCLUSIONS: The present findings suggest that COX5A plays an important role in promoting neurological recovery after HI, and this process is related to TPI up-regulation.

Injection of Aß1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew.

Alzheimer's disease (AD) can incur significant health care costs to the patient, their families, and society; furthermore, effective treatments are limited, as the mechanisms of AD are not fully understood. This study utilized twelve adult male tree shrews (TS), which were randomly divided into PBS and amyloidbetapeptide1-40 (Aß1-40) groups. AD model was established via an intracerebroventricular (icv) injection of Aß1-40 after being incubated for 4 days at 37 °C. Behavioral, pathophysiological and molecular changes were evaluated by hippocampal-dependent tasks, magnetic resonance imaging (MRI), silver staining, hematoxylin-eosin (HE) staining, TUNEL assay and gene sequencing, respectively. At 4 weeks post-injection, as compared with the PBS group, in Aß1-40 injected animals: cognitive impairments happened, and the hippocampus had atrophied indicated by MRI findings; meanwhile, HE staining showed the cells of the CA3 and DG were significantly thinner and smaller. The average number of cells in the DG, but not the CA3, was also significantly reduced; furthermore, silver staining revealed neurotic plaques and neurofibrillary tangles (NFTs) in the hippocampi; TUNEL assay showed many cells exhibited apoptosis, which was associated with downregulated BCL-2/BCL-XL-associated death promoter (Bad), inhibitor of apoptosis protein (IAP), Cytochrome c (CytC) and upregulated tumor necrosis factor receptor 1 (TNF-R1); lastly, gene sequencing reported a total of 924 mobilized genes, among which 13 of the downregulated and 19 of the upregulated genes were common to the AD pathway. The present study not only established AD models in TS, but also reported on the underlying mechanism involved in neuronal apoptosis associated with multiple gene expression.

Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats.

Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, but also significantly enhanced neurons' survival, and attenuated neuronal apoptosis, as well as promoted motor and sensory function recovery in hind limbs. While, overexpression SNCA exhibited the opposite effects. In vitro, cortical neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival and neurite outgrowth, while it was accompanied by reverse efficiency in SNCA-ORF group. In molecular level, SNCA silence induced the upregulation of Bcl-2 and the downregulation of Bax, and the expression of NGF, BDNF and NT3 was substantially upregulated in cortical neurons. Together, endogenous SNCA play a crucial role in motor and sensory function regulation, in which, the underlying mechanism may be linked to the regulation of apoptosis associated with apoptotic gene (Bax, Bcl2) and neurotrophic factors expression (NGF, BDNF and NT3). These finds provide novel insights to understand the role of SNCA in cerebral cortex after SCT, and it may be as a novel treatment target for SCI repair in future clinic trials.

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) improves brain ischemia-induced pulmonary injury in rats associated to TNF-α expression.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. This study explores the effects of transplantation of BMSCs on acute lung injury induced by focal cerebral ischemia and investigates the underlying mechanism. METHODS: Acute lung injury model was induced by middle cerebral artery occlusion (MCAO). BMSCs (with concentration of 1 × 10(6)/ml) were transplanted into host through tail vein 1 day after MCAO. Then, the survival, proliferation and migration of BMSCs in lung were observed at 4 days after transplantation, and histology observation and lung function were assessed for 7 days. Meanwhile, in situ hybridization (ISH), qRT-PCR and western blotting were employed to detect the expression of TNF-α in lung. RESULTS: Neurobehavioral deficits and acute lung injury could be seen in brain ischemia rats. Implanted BMSCs could survive in the lung, and relieve pulmonary edema, improve lung function, as well as down regulate TNF-α expression. CONCLUSIONS: The grafted BMSCs can survive and migrate widespread in lung and ameliorate lung injury induced by focal cerebral ischemia in the MCAO rat models. The underlying molecular mechanism, at least partially, is related to the suppression of TNF-α.

Endogenous TGFß1 Plays a Crucial Role in Functional Recovery After Traumatic Brain Injury Associated with Smad3 Signal in Rats.

Transforming growth factor-ß 1 (TGFß1) has a diverse role in astrogliosis and neuronal survival, but the underlying mechanism remains to be elucidated, especially in traumatic brain injury (TBI). Here, we show that the expression of TGFß1 was increased in the pericontusional region, accompanied with astrogliosis and neuronal loss in TBI rats. Moreover, TGFß1 knockdown not only reduced the number of neurons and inhibited astrogliosis but also resulted in a significant neurological dysfunction in rats with TBI. Subsequently, Smad3, a key downstream signal of TGFß1, was involved in pericontusional region after TBI. These findings therefore indicate that TGFß1 is involved in neuroprotection and astrogliosis, via activation of down stream Smad3 signal in the brain after injury.

[Treatment of upper urinary calculi through novel modular flexible ureteroscope: a report of 36 cases].

OBJECTIVE: To evaluate the feasibility and efficacy of novel modular flexible ureteroscope in the treatment of upper urinary calculi. METHODS: From Nov. 2013 to Jul. 2014, 36 cases of upper urinary calculi were treated with holmium laser lithotripsy through novel modular flexible ureteroscope. The clinical data including the location and diameter of the calculi, time of operation, stone-free rate, complications and hospital stay after operation were analyzed retrospectively. RESULTS: The operation was performed successfully in 34 cases, the average time of operation was 108.5 min (70-145 min), the post-operation hospital stay was 2-5 d (average 2.3 d), and the stone-free rate was 83.33%. No serious complications occurred except postoperative fever in 2 cases and haemorrhage in 1 case. CONCLUSION: The novel modular flexible ureteroscope is a safe and effective medical instrumentation for treatment of upper urinary calculi.

[Comparison of tubeless-percutaneous nephrolithotomy and ureteroscopic lithotripsy in treatment of upper-ureteral calculi sized ≥ 1.5 cm].

OBJECTIVE: To compare the efficacy and safety of tubeless percutaneous nephrolithotomy (tubeless-PCNL) and ureteroscopic lithotripsy (URL) in treatment of impacted upper-ureteral calculi ≥ 1.5 cm in size. METHODS: Patients with ureteral stones sized ≥ 1.5 cm and lodged above the fourth lumbar vertebra who were treated between September 2009 and July 2013 in Peking University People's Hospital were retrospectively analyzed. In the study, 182 patients underwent tubeless-PCNL or URL treatment respectively, and the operation success rates were compared. The duration of operation, intraoperative blood loss(average hemoglobin decrease), complications, mean hospital stay and residual stone rates were also compared. RESULTS: Fifty-four patients underwent tubeless-PCNL treatment,the average stone size was (1.9 ± 0.4) cm,nephrostomy tubes were placed in two patients,and the operation success rate was 96.3%(52/54). In the rest of the 52 patients,and the mean operation time was (30.1 ± 14.8) minutes with an average postoperative hemoglobin decrease of (10.2 ± 6.1) g/L, and the mean hospital stay was (3.0 ± 1.4) days. Only one of the patients had residual fragments (2%). The main complications included minor perirenal hematoma in 1 patient, fever in 2 patients,elevated blood WBC in 11 patients,and analgesics requirement in 3 patients. In the study, 128 patients were treated with URL,the average stone size was (1.7 ± 0.3) cm. 19 procedures failed,and 10 patients were converted to PCNL,extracorporeal shock wave lithotripsy was executed subsequently after double-J stent placement in 5 patients,and migration of calculi or stone fragments happened in 4 patients. The mean operative time was (51.3 ± 25.5) minutes for the remaining 109 patients with a hemoglobin reduction of (5.2 ± 7.2) g/L. The mean hospital stay was (2.9 ± 1.3) days, and residual stones were found in 13 of the 109 patients (11.9%). The main complications included fever in 3 patients, elevated blood WBC in 42 patients, analgesics requirement in 13 patients because of pain in the urethra or flank. The size of the stones between the two group didn't show significant difference,but the success rate of the tubeless-PCNL procedure was significantly higher. Except that hemoglobin decrease was slightly higher in the tubeless-PCNL group,the mean operative time, the rate of residual stones and rate of complications of the tubeless-PCNL group were lower significantly. CONCLUSION: Treating stones above 4th lumbar vertebra larger than 1.5 cm were challenging. It is difficult to treat these stones with URL because of a high probability to fail, but on the contrary, tubeless-PCNL was more likely to be performed successfully. For surgeons experienced with the PCNL technology, treating stones ≥ 1.5 cm with tubeless-PCNL procedure may turn out to be more efficient and with a higher operation success rate, and the risk of complications was lower without lengthening the postoperative hospital stay.

[Diagnosis and treatment of hydrocephalus-accompanied renal calculi complicated with renal tumor: 5 case reports].

OBJECTIVE: To investigate the diagnosis and treatment of renal pelvic tumor combined with renal urinary calculi and hydronephrosis. METHODS: Five patients with renal pelvic tumor who underwent relief of the upper urinary obstruction were reviewed. RESULTS: One of the cases lost the opportunity of surgical therapy when pelvic tumor was detected at the advanced stage, and the other 4 cases had received surgery and were followed up. CONCLUSION: As pelvic tumor progresses rapidly after the renal blood flow is improved, and renal urinary calculi with hydronephrosis relieved; the patients with renal pelvic tumor need early diagnosis, aggressive treatment and close follow-up.

[Percutaneous renal puncture guide by a novel real-time needle-tracking ultrasound system for percutaneous nephrolithotomy: analysis of 16 cases].

OBJECTIVE: To evaluate the feasibility and efficacy of percutaneous renal puncture in percutaneous nephrolithotomy guided by novel needle-tracking ultrasound system. METHODS: From may to october 2013, 16 cases of percutaneous nephrolithotomy were performed under the guidance of ultrasound system. The clinical data including the time of completing percutaneous renal puncture, the color of urine sucked out from the kidney calices, and the complications were analyzed retrospectively. RESULTS: Of the 16 patients, 18 percutaneous renal access were established guided by ultrasound system. All of them were successtul for the first time, and the average time of completing percutaneous renal punctures was (26.90 ± 11.37) s (15 to 54 s). After the operation, the hemoglobin decreased by (9.56 ± 5.27)%(1.41% to 24.06%), and no complications occurred except for postoperative fever in 2 case. CONCLUSION: The novel ultrasound system is a safe and effective technique that can reduce the technical difficulty of percutaneous renal puncture in percutaneous nephrolithotomy.

Transcranial Doppler Ultrasonography detection on cerebral infarction and blood vessels to evaluate hypoxic ischemic encephalopathy modeling.

BACKGROUND: This study aimed to observe changes of rats' brain infarction and blood vessels during neonatal hypoxic ischemic encephalopathy (NHIE) modeling by Transcranial Doppler Ultrasonography (TCD) so as to assess the feasibility of TCD in evaluating NHIE modeling. METHODS: Postnatal 7-days (d)-old Sprague Dawley (SD) rats were divided into the Sham group, hypoxic-ischemic (HI) group, and hypoxia (H) group. Rats in the HI group and H group were subjected to hypoxia-1 hour (h), 1.5 h and 2.5 h, respectively. Evaluation on brain lesion was made based on Zea-Longa scores, hematoxylin-eosin (HE) staining and Nissl staining. The brain infarction and blood vessels of rats were monitored and analyzed under TCD. Correlation analysis was applied to reveal the connection between hypoxic duration and infarct size detected by TCD or Nissl staining. RESULTS: In H and HI modeling, longer duration of hypoxia was associated with higher Zea-Longa scores and more severe nerve damage. On the 1 d after modeling, necrosis was found in SD rats' brain indicated by HE and Nissl staining, which was aggravated as hypoxic duration prolonged. Alteration of brain structures and blood vessels of SD rats was displayed in Sham, HI and H rats under TCD. TCD images for coronal section revealed that brain infarct was detected at the cortex and there was marked cerebrovascular back-flow of HI rats regardless of hypoxic duration. On the 7 d after modeling, similar infarct was detected under TCD at the cortex of HI rats in hypoxia-1 h, 1.5 h and 2.5 h groups, whereas the morphological changes were deteriorated with longer hypoxic time. Correlation analysis revealed positive correlation of hypoxic duration with infarct size detected by histological detection and TCD. CONCLUSIONS: TCD dynamically monitored cerebral infarction after NHIE modeling, which will be potentially served as a useful auxiliary method for future animal experimental modeling evaluation in the case of less animal sacrifice.

Predictive potentials of glycosylation-related genes in glioma prognosis and their correlation with immune infiltration.

Glycosylation is currently considered to be an important hallmark of cancer. However, the characterization of glycosylation-related gene sets has not been comprehensively analyzed in glioma, and the relationship between glycosylation-related genes and glioma prognosis has not been elucidated. Here, we firstly found that the glycosylation-related differentially expressed genes in glioma patients were engaged in biological functions related to glioma progression revealed by enrichment analysis. Then seven glycosylation genes (BGN, C1GALT1C1L, GALNT13, SDC1, SERPINA1, SPTBN5 and TUBA1C) associated with glioma prognosis were screened out by consensus clustering, principal component analysis, Lasso regression, and univariate and multivariate Cox regression analysis using the TCGA-GTEx database. A glycosylation-related prognostic signature was developed and validated using CGGA database data with significantly accurate prediction on glioma prognosis, which showed better capacity to predict the prognosis of glioma patients than clinicopathological factors do. GSEA enrichment analysis based on the risk score further revealed that patients in the high-risk group were involved in immune-related pathways such as cytokine signaling, inflammatory responses, and immune regulation, as well as glycan synthesis and metabolic function. Immuno-correlation analysis revealed that a variety of immune cell infiltrations, such as Macrophage, activated dendritic cell, Regulatory T cell (Treg), and Natural killer cell, were increased in the high-risk group. Moreover, functional experiments were performed to evaluate the roles of risk genes in the cell viability and cell number of glioma U87 and U251 cells, which demonstrated that silencing BGN, SDC1, SERPINA1, TUBA1C, C1GALT1C1L and SPTBN5 could inhibit the growth and viability of glioma cells. These findings strengthened the prognostic potentials of our predictive signature in glioma. In conclusion, this prognostic model composed of 7 glycosylation-related genes distinguishes well the high-risk glioma patients, which might potentially serve as caner biomarkers for disease diagnosis and treatment.

Inhibition of CXCR4: A perspective on miracle fruit seed for Alzheimer's disease treatment.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its causes are currently diverse and not fully understood. In a previous study, we discovered that short-term treatment with miracle fruit seed (MFS) had a therapeutic effect on AD model mice, however, the precise mechanism behind the effect remains unclear. In this research, we aimed to establish the efficacy and safety of long-term use of MFS in AD model mice. A variety of cytokines and chemokines have been implicated in the development of AD. Previous studies have validated a correlation between the expression levels of C-X-C chemokine receptor type 4 (CXCR4) and disease severity in AD. In this research, we observed an upregulation of CXCR4 expression in hippocampal tissues in the AD model group, which was then reversed after MFS treatment. Moreover, CXCR4 knockout led to improving cognitive function in AD model mice, and MFS showed the ability to regulate CXCR4 expression. Finally, our findings indicate that CXCR4 knockout and long-term MFS treatment produce comparable effects in treating AD model mice. In conclusion, this research demonstrates that therapeutic efficacy and safety of long-term use of MFS in AD model mice. MFS treatment and the subsequent reduction of CXCR4 expression exhibit a neuroprotective role in the brain, highlighting their potential as therapeutic targets for AD.