Nanoscale myelinogenesis image in developing brain via super-resolution nanoscopy by near-infrared emissive curcumin-BODIPY derivatives.

Understanding the intricate nanoscale architecture of neuronal myelin during central nervous system development is of utmost importance. However, current visualization methods heavily rely on electron microscopy or indirect fluorescent method, lacking direct and real-time imaging capabilities. Here, we introduce a breakthrough near-infrared emissive curcumin-BODIPY derivative (MyL-1) that enables direct visualization of myelin structure in brain tissues. The remarkable compatibility of MyL-1 with stimulated emission depletion nanoscopy allows for unprecedented super-resolution imaging of myelin ultrastructure. Through this innovative approach, we comprehensively characterize the nanoscale myelinogenesis in three dimensions over the course of brain development, spanning from infancy to adulthood in mouse models. Moreover, we investigate the correlation between myelin substances and Myelin Basic Protein (MBP), shedding light on the essential role of MBP in facilitating myelinogenesis during vertebral development. This novel material, MyL-1, opens up new avenues for studying and understanding the intricate process of myelinogenesis in a direct and non-invasive manner, paving the way for further advancements in the field of nanoscale neuroimaging.

[Efficacy and safety of mini-track, mini-nephroscopy and mini-ultrasonic probe percutaneous nephrolithotomy for the treatment of 1.5-2.5 cm kidney stones].

OBJECTIVE: To investigate the efficacy and safety of mini-track, mini-nephroscopy and mini-ultrasonic probe percutaneous nephrolithotomy (3mPCNL) for the treatment of 1.5-2.5 cm kidney stones. METHODS: The perioperative data and postoperative follow-up data of a total of 25 patients with about 1.5-2.5 cm kidney stones who underwent 3mPCNL under ultrasound guidance in Peking University People's Hospital from November 2023 to January 2024 were retrospectively analyzed. During the matching period, the 25 patients with 1.5-2.5 cm kidney stones receiving standard percutaneous nephrolithotomy (sPCNL) were matched one-to-one according to the criterion that the absolute difference of the maximum diameter of stones between the two groups was less than 1 mm. The operative time, renal function changes, postoperative stone-free rate, hemoglobin changes, and complication rate of the two treatments were compared, and then the effectiveness and safety of 3mPCNL were preliminarily analyzed. RESULTS: There were no significant differences in mean age, preoperative median creatinine, preoperative mean hemoglobin, preoperative mean hematocrit, median stone maximum diameter, and median stone CT density between the 3mPCNL group and the sPCNL group. The median operation time in the 3mPCNL group was 60.0 (45.0-110.0) min, with no statistical significance compared with the sPCNL group, and all the patients underwent single-channel operations. The mean hemoglobin after operation in the 3mPCNL group was (115.3±15.5) mmol/L, and there was no significant difference between the preoperative group and the sPCNL group, and the mean hemoglobin decreased significantly between the sPCNL group and the sPCNL group [(9.5±2.2) mmol/L vs. (10.1±1.9) mmol/L]. The mean hematocrit after operation was (28.0±5.2)%, and the difference was statistically significant compared with that before operation (t=2.414, P=0.020). The mean hematocrit drop was not statistically signi-ficant compared with the sPCNL group (2.3% vs. 2.7%). The median serum creatinine in the 3mPCNL group was 74.0 (51.0-118.0) µmol/L after operation, and the difference was statistically significant compared with that before operation (Z=-2.980, P=0.005). The stone-free rate in the 3mPCNL group and the sPCNL group was 96.0% and 97.3%, respectively, and the mean hospital stay was (4.3± 1.4) d and (5.5±2.0) d, respectively, with the statistical significance (t=0.192, P=0.025). After the operation, one patient in sPCNL group had massive hemorrhage after the nephrostomy tube was removed, which was improved after selective renal artery embolization. One patient in the 3mPCNL group developed mild perirenal hematoma, which was improved after conservative treatment, and no complications were observed in the other patients. CONCLUSION: 3mPCNL in the treatment of 1.5-2.5 cm kidney stones can achieve an effective rate comparable to sPCNL, and can achieve the ideal stone-free rate in a shorter operative time with a lower rate of surgery-related complications.

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.

Mini-track, mini-nephroscopy, mini-ultrasonic probe percutaneous nephrolithotomy and its initial clinical application.

BACKGROUND: To assess the outcome of the mini-track, mini-nephroscopy, mini ultrasonic probe percutaneous nephrolithotomy for upper ureteral and kidney stones. METHODS: We collected data of 53 patients (55 kidney units) who underwent mini-track, mini-nephroscopy, mini-ultrasonic probe percutaneous nephrolithotomy between September 2020 and March 2021. The study included single and upper ureteral stones from 12 kidneys, multiple stones from 28 kidneys, and staghorn stones from 15 kidneys. RESULTS: The mean operative duration was 50.6 min, ranging from 15 to 200 min, whereas the mean lithotripsy and stone removal time was 17.2 min (3-45 min). Moreover, the mean postoperative length of stay was 4.0 days (1-7 days). Besides, the stone-free rate (SFR) of discharge was 89.1% (49/55). The mean hemoglobin drop was 15.3 mg/dL, ranging 1-32 mg/dL. Out of the total cases, only 4 of them displayed minor complications. The outcomes of < 40 mm versus ≥ 40 mm calculi were compared by performing subgroup analysis. The results demonstrated a longer operation duration (65.2 vs. 40.2 min), higher complication rate (13.0% vs. 3.3%), and lower SFR in the ≥ 40 mm calculi subgroup. CONCLUSIONS: In summary, mini-track, mini-nephroscopy, mini-ultrasonic probe percutaneous nephrolithotomy is an effective and safe method to treat patients with upper ureteral and kidney calculi. This is especially significant for the stone size of 20-40 mm, demonstrating excellent SFR and a lower complication rate.

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.

Crossing vessels with suspension versus transposition in laparoscopic pyeloplasty of patients with ureteropelvic junction obstruction: a retrospective study.

PURPOSE: To compare the effects of two different methods of laparoscopic pyeloplasty for the treatment of crossing vessels. METHODS: From January 2016 to August 2019, 33 patients with ureteropelvic junction obstruction (UPJO) underwent laparoscopic pyeloplasty at our center, including 21 men and 12 women, ranging from 14 to 66 years of age. There were 20 and 13 cases on the left and right sides, respectively. Patients underwent laparoscopic pyeloplasty (Anderson-Hynes operation). During the operation, either a Hem-o-lok clip suspension or transposition was used to treat the crossing vessels. The double-J stent was removed 8 weeks after the operation. The clinical data of patients were collected and follow-ups were regularly performed after the operation. RESULTS: All the crossing vessels were successfully preserved, and none of them were severed during the operation. The average operation time was 210.6 ± 58.9 min in this group and the average time to manage the crossing vessel was 8.0 ± 3.5 min, 5.9 ± 1.4 min in the suspension group, and 11.7 ± 3.0 min in the transposition group. The dilation of the affected side was 4.8 ± 1.5 cm before operation and 1.2 ± 1.3 cm 3 months after operation. The difference was statistically significant (P < 0.05). Follow-up to February 2020 showed no significant changes in the kidney size in all patients and hydronephrosis was relieved. CONCLUSION: For UPJO patients with crossing vessel compression, the method of Hem-o-lok suspension or vascular transposition can be used to relieve crossing vascular compression and improve the success of pyeloplasty.

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.

Overexpression of miR-124 Protects Against Neurological Dysfunction Induced by Neonatal Hypoxic-Ischemic Brain Injury.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of lifelong disabilities worldwide, without effective therapies and clear regulatory mechanisms. MicroRNAs (miRNAs) act as a significant regulator in neuroregeneration and neuronal apoptosis, thus holding great potential as therapeutic targets in HIE. In this study, we established the hypoxia-ischemia (HI) model in vivo and oxygen-glucose deprivation (OGD) model in vitro. Zea-longa score and magnetic resonance imaging were applied to verify HI-induced neuronal dysfunction and brain infarction. Subsequently, a miRNA microarray analysis was employed to profile miRNA transcriptomes. Down-regulated miR-124 was found 24 h after HIE, which corresponded to the change in PC12, SHSY5Y, and neurons after OGD. To determine the function of miR-124, mimics and lentivirus-mediated overexpression were used to regulate miR-124 in vivo and in vitro, respectively. Our results showed that miR-124 overexpression obviously promoted cell survival and suppressed neuronal apoptosis. Further, the memory and neurological function of rats was also obviously improved at 1 and 2 months after HI, indicated by the neurological severity score, Y-maze test, open field test, and rotating rod test. Our findings showed that overexpression of miR-124 can be a promising new strategy for HIE therapy in future clinical practice.

Outcome of Selective Renal Artery Embolization in Managing Severe Bleeding after Percutaneous Nephrolithotomy.

OBJECTIVES: The aim of this study was to evaluate the characteristics of the renal arterial segment bleeding and assess the outcome of selective renal artery embolization (SRAE). METHODS: Data on 35 patients in whom SRAE was performed after percutaneous nephrolithotomy (PCNL) from January 2005 to December 2015 in our institute were retrospectively analyzed. All patients had severe bleeding but failed to respond to conservative therapy. RESULTS: Forty-four SRAEs were performed in 35 patients (36 kidney units) after PCNL. The findings of 44 renal arteriographies before embolization revealed bleeding in 44 renal artery branch segments. Upper artery segment bleeding in 0, upper and anterior segment bleeding in 3, lower and anterior artery segment bleeding in 6, lower artery segment bleeding in 9, posterior artery segment bleeding in 24, and negative finding in 2 patients. Renal arteriography revealed pseudoaneurysms in 20 (45.5%) patients, arteriovenous fistulas in 6 (13.6%) patients, renal artery branch laceration in 16 (36.4%) patients, and negative angiography finding in 2 (4.5%) patients. Acute bleeding in 7 patients (20.0%) and delayed bleeding in 28 patients (80.0%) were observed. The target vascular lesions were successfully treated by embolization in the first time in 28 cases. Six patients underwent 2 sessions and 1 had 3 sessions. New vascular lesions were the most common cause of failure of initial SEAE in our hospital. Abnormal renal function was observed in 5 patients, and they recovered to preoperative or normal level within 3 weeks. CONCLUSIONS: The posterior artery segment of the kidney is the most common bleeding site due to the choice of puncture site. Delayed bleeding (>24 h) was the most common type of bleeding. SRAE is an effective and safe method to treat the severe bleeding after PCNL.

Challenges and management of laparoscopic treatment of pyonephrosis caused by calculi.

BACKGROUND: Calculous pyonephrosis is a disease characterized by infectious hydronephrosis associated with pyogenic destruction of the renal parenchyma, with complete or almost complete loss of renal function. METHODS: The clinical data of laparoscopic nephrolithotomy performed at Peking University People's Hospital from May 2017 to June 2020 were analyzed retrospectively. Eight patients (2 men; 6 women) aged 27 to 65 years (average age, 45.8 years) were included. Among them, 7 patients were treated with retroperitoneal approach and 1 patient by transperitoneal approach. All patients had received more than one endoscopic lithotripsy before nephrectomy. Renal dynamic imaging and computed tomography revealed the absence of function in pyonephrosis before nephrectomy. General clinical data and perioperative data were recorded. All nephrectomies were performed by the same physician. RESULTS: Laparoscopic surgery was successfully performed in 7 patients; however, 1 patient underwent open surgery because of bleeding. The operation time, average operation time, and blood loss were 1.5-4.5 h, 3.4 h, and 100-1000 ml (average, 300 ml), respectively. The postoperative pathology showed inflammatory renal disease in 6 patients, xanthogranulomatous pyelonephritis in 1 patient, and high-grade urothelial cancer in 1 patient. The average postoperative hospital stay was 5.3 days. One patient had a Clavien-Dindo Grade IIIb complication (severe hematuria), which required laparotomy, and was found that there was bleeding of ureteral stump. None of the patients experienced poor healing of endoscopic wounds. CONCLUSION: For patients with complicated calculous pyonephrosis, renal inflammation could not be effectively controlled, and renal function was seriously damaged. Thus, kidneys should be immediately resected. With laparoscopy, patients may recover quickly, but surgeons require enough experience when performing laparoscopy to achieve safety.

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.