Registration study for the prevention and treatment of cerebral hemorrhage using naoxueshu oral liquid: Protocol for a research study.

BACKGROUND: Naoxueshu oral liquid is the only approved drug for acute treatment of cerebral hemorrhage in China. It has been used widely for the treatment of acute ischemic stroke and acute hemorrhagic stroke. However, safety and efficacy data on the early use of Naoxueshu oral liquid are lacking. The main purpose of this study is to observe the benefit and safety of early use of Naoxueshu oral liquid (< 72 h of cerebral hemorrhage) and offer evidence into the potential superiority of Naoxueshu oral liquid in patients with hemorrhagic stroke, and its healthcare costs. METHODS: This registration study for the prevention and treatment of cerebral hemorrhage using Naoxueshu oral liquid will be a quantitative, prospective, multicenter, observational clinical registry study. We aim to register 2000 patients with cerebral hemorrhage within 7 days of disease onset. This study will be an observational study and not interfere with the medication regimen of participants. Hence, we will not allocate patients. The main observation indicators will be the hematoma volume and the proportion of reduction 14 days post-cerebral hemorrhage (or at hospital discharge), onset of new stroke (ischemic stroke, hemorrhagic stroke) within 12 months of disease onset, independence in everyday life activities (modified Rankin Scale score ≤ 2), total cost during hospitalization, and treatment costs. CONCLUSION: This registration study will offer strong evidence for the efficacy and safety of Naoxueshu oral liquid for the prevention and treatment of cerebral hemorrhage, particularly with regard to early use (72 h after onset). It will offer evidence into the potential advantages of Naoxueshu oral liquid in patients with hemorrhagic stroke, including healthcare costs.

The clinical characteristics of focal acute pancreatitis based on imaging diagnosis: comparison with non-localized acute pancreatitis- a preliminary result.

BACKGROUND: Focal acute pancreatitis is a special type of acute pancreatitis, which diagnosis is based on image showing a focal mass formation in the pancreas. For acute pancreatitis with or without focal inflammatory enlargement, little is known on differences between them. Our purpose was to find differences between focal acute pancreatitis and non-localized acute pancreatitis. METHODS: We reviewed the medical records of a total of 24 patients diagnosed with focal acute pancreatitis by imaging and clinical diagnosis, and 27 cases of acute pancreatitis which manifest non-localized pancreas inflammation were selected as the control group. The differences of the two groups were compared to describe their clinical characteristics. RESULTS: Differences in bloating (4.2% VS 29.6%,P = 0.026), abdominal tenderness (58.3% VS 85.2%,P = 0.032), peripheral blood neutrophil ratio (60.1 ± 23.3VS 75.9 ± 12.6,P = 0.004), serum D-Dimer (0.40(0.25,0.98) VS 1.59(0.49,4.63),P = 0.008), serum GGT (40(25,91) VS120(22,383),P = 0.046), serum amylase(435(241,718) VS 591(394,1333),P = 0.044) and lipase(988(648,1067) VS 1686(525,2675),P = 0.027) between focal acute pancreatitis and non-localized acute pancreatitis groups were statistically significant. However, difference of the severity of two groups was not statistically significant (P = 1.000). CONCLUSION: Compared with non-localized acute pancreatitis, changes in symptoms, signs and laboratory indicators of focal acute pancreatitis are non-obvious, however, there was no significant difference in the severity of two groups, indicating that we should pay more attention to diagnosis of focal acute pancreatitis in clinical practice.

[Research progress in mechanism of puerarin in treating vascular dementia].

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aß injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.

Ultrasound increases the success rate of spinal needle placement through the epidural needle during combined spinal-epidural anaesthesia: A randomised controlled study.

BACKGROUND: Combined spinal-epidural anaesthesia (CSEA) using a needle-through-needle technique is currently widely used. However, successful epidural needle placement does not mean a successful spinal needle placement during CSEA. Whether ultrasound assistance could increase the first-pass success rate of spinal needle placement for CSEA remains unknown. OBJECTIVE: The aim of this study was to investigate if ultrasound assistance could increase the first-pass success rate of spinal needle placement through the epidural needle during CSEA performed by experienced anaesthesiologists in patients undergoing caesarean section. DESIGN: A prospective, randomised, double-blind study. SETTING: Single centre, Department of Anaesthesiology, Shengjing Hospital, China Medical University, China, from June 2019 to September 2019. PATIENTS: A total of 185 patients (aged 24 years to 52 years, American Society of Anesthesiologists grade (ASA) II-III, 38 to 40 weeks gestation) scheduled to undergo elective caesarean section under CSEA were enrolled. INTERVENTION: The patients were randomised to either an ultrasound group (patients received a preprocedural ultrasound scan, and the puncture site was identified by ultrasound imaging) and a palpation group (patients received a sham procedural ultrasound scan, and the puncture site was identified by conventional palpation). MAIN OUTCOME MEASURES: The primary outcome measure was the first-pass success rate for spinal needle placement through the epidural needle. Secondary outcome measures were total duration of CSEA, time required for successful epidural needle and spinal needle placement, number of epidural needle redirections and complications. RESULTS: Preprocedural ultrasound imaging significantly increased the first-pass success rate of spinal needle placement through the epidural needle compared with conventional palpation (93.8 vs. 68.8%, P < 0.001). Preprocedural ultrasound imaging also decreased the total duration of CSEA (186.9 ±â€Š37.1 vs. 213 ±â€Š60.4 s, P = 0.0015) and the time required for successful spinal needle placement (78.3 ±â€Š22.9 vs. 100.1 ±â€Š53.7 s, P < 0.01) compared with conventional palpation. Fewer patients in the ultrasound group needed epidural needle redirections during the spinal needle placement procedure than in the palpation group (four patients vs. 20 patients, P < 0.01). CONCLUSION: For experienced anaesthesiologists, preprocedural ultrasound imaging significantly increased the first-pass success rate of spinal needle placement through the epidural needle for obstetric patients undergoing caesarean section under CSEA. TRIAL REGISTRATION: chictr.org.cn, identifier: ChiCTR1900024132.

Perioperative effects of caudal block on pediatric patients in laparoscopic upper urinary tract surgery: a randomized controlled trial.

BACKGROUND: While caudal block has been widely used during pediatric lower limbs and lower abdominal surgeries, few studies to date have evaluated the perioperative effects of caudal block on pediatric patients in laparoscopic upper urinary tract surgery. METHODS: Ninety-six pediatric patients, aged 6 months to 7 years, ASA grade I-II, scheduled to undergo laparoscopic upper urinary tract surgery, were randomized to a non-block group (no caudal block performed), an ROP1.0 group (patients received 1.0 mL/kg of 0.15% ropivacaine) and an ROP1.3 group (patients received 1.3 mL/kg of 0.15% ropivacaine). The primary outcome variable was perioperative fentanyl use. The secondary outcome variables were pain score, hemodynamic fluctuation, the number of patients needing rescue fentanyl and side effects. RESULTS: Caudal block with 1.3 mL/kg of 0.15% ropivacaine significantly decreased perioperative fentanyl usage (ROP 1.3 vs. non-caudal block, P < 0.01; ROP 1.3 vs. ROP 1.0, P < 0.05). Moreover, patients in the ROP1.3 group, compared to those without, displayed more stable hemodynamics, lower pain score in the PACU and 8 h after operation, less demand for rescue fentanyl, shorter time of PACU stay. CONCLUSIONS: Caudal block with 1.3 mL/kg of 0.15% ropivacaine reduced perioperative fentanyl use during laparoscopic upper urinary tract surgery on pediatric patients and produced good postoperative analgesia when compared with no caudal block and caudal block with 1.0 mL/kg of 0.15% ropivacaine. TRIAL REGISTRATION: Clinical trial number: ChiCTR1800015549, chictr.org.cn.

A Murine Model for Human ECO Syndrome Reveals a Critical Role of Intestinal Cell Kinase in Skeletal Development.

An autosomal-recessive inactivating mutation R272Q in the human intestinal cell kinase (ICK) gene caused profound multiplex developmental defects in human endocrine-cerebro-osteodysplasia (ECO) syndrome. ECO patients exhibited a wide variety of skeletal abnormalities, yet the underlying mechanisms by which ICK regulates skeletal development remained largely unknown. The goal of this study was to understand the structural and mechanistic basis underlying skeletal anomalies caused by ICK dysfunction. Ick R272Q knock-in transgenic mouse model not only recapitulated major ECO skeletal defects such as short limbs and polydactyly but also revealed a deformed spine with defective intervertebral disk. Loss of ICK function markedly reduced mineralization in the spinal column, ribs, and long bones. Ick mutants showed a significant decrease in the proliferation zone of long bones and the number of type X collagen-expressing hypertrophic chondrocytes in the spinal column and the growth plate of long bones. These results implicate that ICK plays an important role in bone and cartilage development by promoting chondrocyte proliferation and maturation. Our findings provided new mechanistic insights into the skeletal phenotype of human ECO and ECO-like syndromes.

Link protein N-terminal peptide and fullerol promote matrix production and decrease degradation enzymes in rabbit annulus cells.

PURPOSE: Intervertebral disc degeneration is a major cause of back pain. Novel therapies for prevention or reversal of disc degeneration are needed. It is desirable for potential therapies to target both inflammation and matrix degeneration. MATERIALS AND METHODS: The combined regenerative potential of link protein N-terminal peptide (LN) and fullerol on annulus fibrosus (AF) cells was evaluated in a 3D culture model. RESULTS: Interleukin-1α (IL-1α)-induced AF cell degeneration was counteracted by fullerol, LN, and fullerol + LN, with the latter having the greatest effect on matrix production as evaluated by real-time polymerase chain reaction and glycosaminoglycan assay. IL-1α-induced increases in pro-inflammatory mediators (interleukin-6 and cyclooxygenase-2) and matrix metalloproteinases (MMP-1, -2, -9, and -13) were also counteracted by fullerol and LN. CONCLUSION: Our data demonstrate that LN and fullerol individually, and in combination, promote matrix production and have anti-inflammatory and anti-catabolic effects on AF cells.

A novel culture platform for fast proliferation of human annulus fibrosus cells.

Tissue engineering provides a promising approach to treat degenerative disc disease, which usually requires a large quantity of seed cells. A simple and reliable in vitro culture system to expand seed cells in a timely fashion is necessary to implement the application clinically. Here, we sought to establish a cost-effective culture system for expanding human annulus fibrosus cells using extracellular matrix (ECM) proteins as culture substrates. Cells were cultured onto a plastic surface coated with various types of ECMs, including fibronectin, vitronectin, collagen type I, gelatin and cell-free matrix deposited by human nucleus pulposus cells. AF cell morphology, growth, adhesion and phenotype (anabolic and catabolic markers) were assessed by microscopy, real-time RT-PCR, western blotting, zymography, immunofluorescence staining and biochemical assays. Fibronectin, collagen and gelatin promoted cell proliferation and adhesion in a dose-dependent manner. Fibronectin elevated mRNA expression of proteoglycan and enhanced glycosaminoglycan production. Both collagen and gelatin increased protein expression of type II collagen. Consistent with increased cell adhesion, collagen and fibronectin promoted formation of focal adhesion complexes in the cell-matrix junction, suggesting enhanced binding of the actin network with both ECM substrates. On the other hand, fibronectin, collagen and gelatin decreased expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in media. Finally, a mixture of fibronectin (1.7 µg/mL) and collagen (1.3 µg/mL) was identified as the most promising in vitro culture substrate system in promoting proliferation and maintaining anabolic-catabolic balance. Our method provides a simple and cost-effective platform for tissue engineering applications in intervertebral disc research.

Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe.

Differential diagnosis of chronic post-traumatic osteomyelitis (CPO) from aseptic inflammation remains challenging, since both pathological processes share similar clinical symptoms. Here we utilized a novel targeted metallofullerene nanoparticle based magnetic resonance imaging (MRI) probe IL-13-TAMRA-Gd3N@C80(OH)30(CH2CH2COOH)20 to detect CPO in mouse tibia via overexpressed IL-13Rα2 receptors. The functionalized metallofullerene was characterized by X-ray photoelectron spectroscopy. Upon lipopolysaccharide (LPS) stimulation, macrophage Raw 264.7 cells showed elevated IL-13Rα2 expression via immunofluorescence staining and increased MRI probe binding via built-in TAMRA fluorescence imaging. Trauma was induced in both tibia of mice and bacteria soaked suture was inserted into the right tibia to initiate infection. During the acute phase (1.5 weeks), luminol-bioluminescence imaging revealed much higher myeloperoxidase activity in the infected tibia compared to the sham. In the chronic phase (4 weeks), X-ray radiography illustrated bone deformation in the infected tibia compared to the sham. With T1 weighted sequences, the probe clearly exhibited hyperintensity in the infection foci at both acute and chronic phases, which was not observed in the sham tibia. Histological analysis revealed severe bone structural destruction and massive inflammatory cell infiltration in the infected tibia. Immunohistochemistry confirmed abundant expression of IL-13Rα2 in the infection site. In summary, we developed a noninvasive imaging approach to detect and differentiate CPO from aseptic inflammation using a new IL-13Rα2 targeted metallofullerene MRI probe. In addition, for the first time, IL-13Rα2 was investigated as a unique biomarker in the context of osteomyelitis. Our data established a foundation for the translational application of this MRI probe in the clinical differentiation of CPO.

Curcin C, a novel type I ribosome-inactivating protein from the post-germinating cotyledons of Jatropha curcas.

A novel type I ribosome-inactivating protein (RIP), designated as curcin C, was purified from Jatropha curcas, an important feedback source of bio-fuel. Molecular mass and isoelectric point of curcin C were 31.398 kDa and 7.12 as detected by MALTI-TOF assay and capillary electrophoresis assay, respectively. N-terminal sequence and LC-MS/MS analyses confirmed that curcin C is a type I RIP having high homology, but not the exactly the same with curcin, another type 1 RIP isolated from the endosperm of J. curcas. It exhibited N-glycosidase activity and in vitro translation inhibition activity. Moreover, curcin C displayed a strong selectively anti-tumor activity on human cancer cells. Its cytotoxicity against osteosarcoma cell line U20S is even higher than that of Paclitaxel with IC50 of 0.019 µM. Purification and identification of curcin C not only suggested its potential in natural anticancer drug development, but also provide chance to understanding different cytotoxic action among different RIPs.

Nanoparticle fullerol alleviates radiculopathy via NLRP3 inflammasome and neuropeptides.

The present study aimed to evaluate the analgesic effect of the antioxidant nanoparticle fullerol in a mouse radiculopathy and a dorsal root ganglion (DRG) culture models. Intervertebral disk degeneration causes significant hyperalgesia and nerve inflammation. Pain sensitization and inflammatory reaction were counteracted by fullerol when disk material was bathed in 10 or 100µM of fullerol prior to implantation. Immunohistochemistry showed similar massive IBA1 positive macrophage infiltration surrounding implanted disk material among groups, but IL-1ß and IL-6 expression was decreased in the fullerol treated group. In the DRG explant culture, after treatment with TNF-α, the expression of IL-1ß, NLRP3, and caspase 1 was significantly increased but this was reversed by the addition of fullerol. In addition, fullerol also decreased the expression of substance P and CGRP in the cultured DRGs. Nanoparticle fullerol effectively counteracts pain sensitization and the inflammatory cascade caused by disk degeneration.

Isoflurane postconditioning induces concentration- and timing-dependent neuroprotection partly mediated by the GluR2 AMPA receptor in neonatal rats after brain hypoxia-ischemia.

BACKGROUND: It has been demonstrated that preconditioning with 1.5 % isoflurane reduces hypoxia/ischemia (HI)-induced brain loss/injury in neonatal rats. Ca(2+) influx mediated by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) is involved in HI-induced neuronal death. Here, we investigated the effective concentrations and time windows for neuroprotection by isoflurane postconditioning in neonatal rats after brain HI and determined whether GluR2-containing AMPARs mediate this neuroprotection. METHODS: Seven-day-old Sprague-Dawley (SD) rats were randomly divided into eight groups (n = 40 in each). The rats underwent left common carotid arterial ligation (brain HI) or sham surgery, followed by exposure to 8 % oxygen for 2 h at 37 °C in a thermoregulated environment. Post-conditioning with 1, 1.5, or 2 % isoflurane for 30 min was performed immediately after brain HI. Others were post-treated with 1.5 % isoflurane for 30 min at 3, 6, and 12 h after brain HI. The weight ratio, neuronal density ratio in the ventral posteromedial thalamic nucleus, and retrosplenial granular cortex of left to right cerebral hemispheres at 7 days after brain HI were evaluated in all groups. Cerebral hemispheres were harvested for Western-blot analysis of GluR2 on the cellular membranes 24 h after HI or sham surgery in neonatal rats from the sham group, the HI group, and the HI + immediate exposure to the 1.5 % isoflurane group. In another experiment, the function of learning and memory were assessed in adolescence (4 weeks) using Morris water maze. RESULTS: Compared with the control (sham) group, brain HI decreased the weight ratio and the neuronal density ratio in the ventral posteromedial thalamic nucleus and the retrosplenial granular cortex of the left to right cerebral hemispheres (p < 0.05). These effects of brain HI were reduced by postconditioning with 1.5 or 2 % isoflurane for 30 min within 6 h of HI, which coincided with the results of Morris water maze. GluR2 protein expression on cellular membranes was reduced after HI compared with sham surgery group (p < 0.05); this down-regulation was attenuated by isoflurane postconditioning. CONCLUSIONS: Postconditioning with 1.5 and 2 % isoflurane affords neuroprotection in neonatal rats. The time window for isoflurane postconditioning to be effective against neonatal HI-induced brain injury was 0-6 h after HI. This protection may be mediated by GluR2-containing AMPARs.

[Correlations between constipation and the axial symptoms, related motor symptoms in Parkinson's disease].

OBJECTIVE: To investigate the clinical characteristics of Parkinson's Disease (PD) patients with constipation and explore the correlation between constipation and motor symptoms. METHODS: The demographic data of outpatients with PD in our hospital was collected. According to Rome Ⅲ criteria, we evaluated the status of constipation in PD patients. Unified Parkinson's disease rating scale part Ⅲ (UPDRSⅢ), mini-mental state examination (MMSE) were performed in all the included patients. RESULTS: Among the 158 recruited PD patients, 96 (60.8%) patients had constipation. Among these patients, 41(42.7%) patients experienced constipation before motor symptoms. Compared to those without constipation, PD patients with constipation had higher axial scores (6.8±3.4 vs 4.3±2.5, t=-4.887, P=0.000) and gait/postural stability scores (3.9±2.4 vs 2.4±1.5, t=-4.529, P=0.000), higher proportion of axial and gait/postural stability scores in UPDRSⅢ (32%±11% vs 25%±12%, t=-3.485, P=0.001; 18%±9% vs 15%±10%, t=-2.278, P=0.024), more rapid progression of axial and gait/postural stability symptoms (P<0.05). However, there were no differences in other sub-scores and progression of motor symptoms between the two groups (P>0.05). The PD patients with constipation preceding motor symptoms had higher proportion of axial and gait/postural stability scores in UPDRSⅢ (35%±11% vs 30%±10%, t=2.167, P=0.033; 21%±9% vs 16%±8%, t=2.733, P=0.008), indicating these patients may progress more rapidly, meanwhile, they had later onset age, shorter disease duration (P<0.05). Unconditioned Logistic regression showed that axial score was major influencing factor of constipation in PD patients (P=0.000, OR=1.330). CONCLUSIONS: PD patients with constipation have severer axial symptoms, indicating the progression of these patients is relatively rapid, especially those with constipation preceding motor symptoms. It is suggested that axial symptoms and constipation are acted as interactional factors in PD.

Association between heavy metals exposure (cadmium, lead, arsenic, mercury) and child autistic disorder: a systematic review and meta-analysis.

Background: Studies have found that toxic heavy metals exposure could induce the generation of reactive oxygen species (ROS), and is of epigenetic effect, which might be associated with the occurrence of Autistic Disorder (ASD). This systematic review and meta-analysis aims to elucidate the association between exposure to 4 heavy metals, cadmium (Cd), lead (Pb), arsenic(As), and mercury (Hg), and the occurrence of ASD in children. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library, from their inception to October 2022, for epidemiological investigations that explore the association between exposure to Cd, Pb, As, or Hg and the occurrence of child ASD. Results: A total of 53 studies were included, involving 5,054 individuals aged less than 18 (2,533 ASD patients and 2,521 healthy controls). Compared with the healthy controls, in hair and blood tests, concentrations of the 4 heavy metals were significantly higher in the ASD group than in the healthy control group, and the differences in Pb, arsenic and Hg were statistically significant (P < 0.05). In the urine test, concentrations of arsenic and Hg were significantly higher in the ASD group than in the healthy control group (P < 0.05), while the results of Cd and Pb were opposite to those of arsenic and Hg (P > 0.05). Subgroup analysis for geographic regions showed that ASD patients in Asia and Europe had higher concentrations of the 4 heavy metals, compared with the healthy controls, in which the differences in Pb, arsenic, and Hg were statistically significant (P < 0.05), while in North America, the healthy controls had higher Cd, arsenic, and Hg concentrations (P > 0.05). Conclusion: Compared with the healthy control group, the ASD group had higher concentrations of Cd, Pb, arsenic, and Hg. These 4 heavy metals play different roles in the occurrence and progression of ASD. Moreover, there is significant heterogeneity among the included studies due to controversies about the study results among different countries and regions and different sources of detection materials. The results of this study firmly support the policies to limit heavy metals exposure, especially among pregnant women and young children, so as to help reduce the incidence of ASD.

Ketamine counteracts sevoflurane-induced depressive-like behavior and synaptic plasticity impairments through the adenosine A2A receptor/ERK pathway in rats.

Ketamine is an ionic glutamic acid N-methyl-d-aspartate receptor (NMDAR) antagonist commonly used in clinical anesthesia, and its rapid and lasting antidepressant effect has stimulated great interest in psychology research. However, the molecular mechanisms underlying its antidepressant action are still undetermined. Sevoflurane exposure early in life might induce developmental neurotoxicity and mood disorders. In this study, we evaluated the effect of ketamine against sevoflurane-induced depressive-like behavior and the underlying molecular mechanisms. Here, we reported that A2AR protein expression was upregulated in rats with depression induced by sevoflurane inhalation, which was reversed by ketamine. Pharmacological experiments showed that A2AR agonists could reverse the antidepressant effect of ketamine, decrease extracellular signal-regulated kinase (ERK) phosphorylation, reduce synaptic plasticity, and induce depressive-like behavior. Our results suggest that ketamine mediates ERK1/2 phosphorylation by downregulating A2AR expression and that p-ERK1/2 increases the production of synaptic-associated proteins, enhancing synaptic plasticity in the hippocampus and thereby ameliorating the depressive-like behavior induced by sevoflurane inhalation in rats. This research provides a framework for reducing anesthesia-induced developmental neurotoxicity and developing new antidepressants.

Median effective dose of ropivacaine for prophylactic cervical cerclage in Chinese women: a dose-finding study.

BACKGROUND: Although intrathecal ropivacaine has been widely used for caesarean delivery, there are limited data for the use of ropivacaine for prophylactic cervical cerclage. We sought to determine the median effective dose of intrathecal ropivacaine for prophylactic cervical cerclage in 50% of patients (ED50) and the calculated dose required for successful block in 95% of patients (ED95). METHODS: We included Chinese women scheduled for prophylactic cervical cerclage under combined spinal-epidural (CSE) anaesthesia in the first or second trimester. A predetermined dose of intrathecal isobaric ropivacaine was administered. If this determined dose achieved an effective block at a level not lower than T12, the next dose was decreased by 0.5 mg. Otherwise, the next dose was increased by 0.5 mg. The primary outcome was the ED50 of intrathecal ropivacaine. Secondary outcomes included the calculated ED95, time from CSE to the start of surgery and so on. RESULTS: Forty patients were included in the study, 23 (57.5%) of 40 received an effective block only with intrathecal ropivacaine, while 17 (42.5%) patients needed extra epidural lidocaine to achieve a successful block. The ED50 of intrathecal ropivacaine confirmed by isotonic regression was 6.9 mg (95% CI, 6.68 to 7.12 mg), and the calculated ED95 was 7.8 mg (95% CI, 7.69 to 10.05 mg). When an effective block was achieved with intrathecal ropivacaine alone, the time to resolution of the sensory and motor blocks was 90 (75-100) min and 90 (60-100) min, respectively. CONCLUSIONS: The ED50 of intrathecal ropivacaine for prophylactic cervical cerclage was 6.9 mg. Intrathecal ropivacaine (7.8 mg) is likely to produce successful anaesthesia in 95% of patients undergoing prophylactic cervical cerclage. TRIAL REGISTRATION NUMBER: ChiCTR2100051418.

Exploring the relationship between intestinal flora and the pathological mechanism of myopia in adolescents from the perspective of Chinese and Western medicine: A review.

The etiology of adolescent myopia involves genetic and environmental factors. The pathological mechanism of modern medicine includes blood perfusion, changes in blood molecules, neurotransmitters, and sclera remodeling. Chinese medicine believes that myopia is mainly related to the deficiency of liver blood and spleen and stomach disorders. The prevention and treatment of myopia in adolescents are very important, but in terms of the current incidence of myopia in adolescents and the level of clinical diagnosis and treatment, its prevention and treatment are insufficient. Modern medicine and traditional Chinese medicine both pay attention to integrity, so adolescent myopia should not only pay attention to eye changes but also pay attention to other body systems and other aspects of change. Intestinal flora has become a research hotspot in recent years, and it has been found that it is closely associated with multi-system and multi-type diseases. No studies have directly investigated the link between Intestinal flora and myopia in adolescents. Therefore, by summarizing the pathological mechanism of adolescent myopia and the connection between intestinal flora and the pathological mechanism of adolescent myopia, this paper analyzes the possible pathological mechanism of the influence of intestinal flora on adolescent myopia, providing a theoretical basis for future studies on the correlation between changes of intestinal flora and its metabolites and the incidence of adolescent myopia, which is of great significance for the study on the risk prediction of adolescent myopia.

Meta-analysis of repetitive transcranial magnetic stimulation combined with task-oriented training on upper limb function in stroke patients with hemiplegia.

BACKGROUND: To evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with task-oriented training (TOT) on upper limb function in stroke patients with hemiplegia. METHODS: A systematic review and meta-analysis was performed using PRISMA guidelines. Computer searches of PubMed, Cochrane Library, Embase, Web of science, China Knowledge Network, Wanfang, and Wipu databases were conducted from the time of database creation to October 27, 2022. Clinical trials meeting the inclusion criteria were screened, with rTMS combined with TOT in the test group and other therapies in the control group. Literature screening and data extraction were performed independently by 2 investigators, and meta-analysis was performed using Stata software after quality evaluation of the literature. RESULTS: Meta-analysis results showed that repeated transcranial magnetic stimulation combined with TOT was more effective in box and block test (I2 = 0%, P = .820, 95% confidence interval [CI] [-0.20, 0.88]), Fugl-Meyer Assessment (I2 = 0%, P = .569, 95% CI [0.88, 1.26]), and modified Barthel Index (I2 = 39.9%, P = .189, 95% CI [0.45, 1.03]) were not significantly different from controls, and the efficacy was significantly better in motor evoked potentials (I2 = 86.5%, P < .001, 95% CI [-1.38, -0.83]). CONCLUSIONS: Data analysis clarified the efficacy of rTMS) combined with TOT on upper extremity motor function disorders after stroke, but there was no significant difference between the efficacy in box and block test, Fugl-Meyer Assessment, and modified Barthel Index and the efficacy in motor evoked potentials between rTMS and the control group, suggesting that the neuro plasticizing effect of rTMS may translate into functional improvement by promoting neuro electrical signaling.

Identification of Potential Immune Checkpoint Inhibitor Targets in Gliomas via Bioinformatic Analyses.

BACKGROUND: Glioma is a common tumor originating from the glial cells of the brain. Immune checkpoint inhibitors can potentially be used to treat gliomas, although no drug is currently approved. METHODS: The expression levels of the immune checkpoint genes in glioma and normal tissues, and their correlation with the IDH mutation status and complete 1p/19q codeletion, were analyzed using The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Survival analyses were conducted using the CGGA database. Protein-protein interaction and functional enrichment analyses were performed via the STRING database using GO, KEGG, and Reactome pathways. The correlation between the immune checkpoints and the immune cell infiltration was determined using the TISIDB and TIMER databases. RESULTS: HAVCR2 was overexpressed in the gliomas compared to normal brain tissues, as well as in the high-grade glioma patients and significantly downregulated in IDH mutant or 1p/19q codeletion patients. Overexpression of HAVCR2 was associated with poor survival in tumor grades II, III, and IV and was the most correlated with immune infiltration of B and T cells. CONCLUSION: HAVCR2 can be a potential therapeutic target for cancer immunotherapy for glioma patients.

Dexmedetomidine and Ketamine Attenuated Neuropathic Pain Related Behaviors via STING Pathway to Induce ER-Phagy.

Our previous work indicated that ER-phagy level had altered in spinal nerve ligation (SNL) rats. In this study, we investigated whether dexmedetomidine or ketamine exhibits anti-anxiety or anti-nociceptive effects via modulation of the spinal STING/TBK pathway to alter ER-phagy in SNL rats. We evaluated the analgesic and anti-anxiety effects of ketamine and dexmedetomidine in SNL rats. 2'3'-cGAMP (a STING pathway agonist) was administrated to investigate whether enhanced spinal STING pathway activation could inhibit dexmedetomidine or ketamine treatment effects in SNL rats. Analgesic effects were assessed with the mechanical withdrawal threshold (MWT) and anti-anxiety effects were measured via an open field test (OFT). Protein expression levels were evaluated by immunoblotting. Distribution and cellular localization of Grp78 (ER stress marker) were evaluated by confocal immunofluorescence. SNL induced mechanical hypersensitivity and anxiety in rats; dexmedetomidine and ketamine both provided analgesia and anti-anxiety effects in SNL rats. Furthermore, the STING pathway was involved in the modulation of ER stress and ER-phagy in SNL rats and dexmedetomidine and ketamine alleviated ER stress by inhibiting STING pathway to enhance ER-phagy. Thus, both ketamine and dexmedetomidine provided anti-anxiety and anti-nociceptive effects by alleviating ER stress through the inhibition of the STING/TBK pathway to modulate spinal ER-phagy in SNL rats.