Meta-analysis of clinical risk factors of patients with systemic lupus erythematosus complicated with invasive fungal infection.

BACKGROUND: To systematically evaluate the clinical risk factors of patients with systemic lupus erythematosus (SLE) complicated with invasive fungal infection (IFI) among patients. METHODS: A meta-analysis was performed of all the literatures germane to estimate the clinical risk factors of patients with SLE complicated with IFI from published clinical trials from 1990 to April 2022. Mean differences, odds ratio and 95% confidence intervals were calculated, and the meta-analysis was conducted with Stata 12.0 software (StataCorp, College Station, TX). RESULTS: A total of 14 clinical research involving 1129 patients were included. The results of meta-analysis demonstrated that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors associated with IFI in SLE patients. However, age, sex, course of disease, leukopenia, lymphopenia, C- reactive protein and hypoproteinemia were not the risk factors associated with IFI in patients with SLE. CONCLUSION: Our results indicate that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors for IFI in SLE patients. However, high quality of multicenter, large sample size-controlled trials are needed to validate the result.

Effects of ceftriaxone on Nrf2/GPX4 pathway and ferroptosis of cerebral cortex in early brain injury of rats with subarachnoid hemorrhage / 中华行为医学与脑科学杂志

Objective:To investigate the effects of ceftriaxone(CTX) on nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4) pathway and ferroptosis in early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Forty-eight clean grade male SD rats were randomly divided into sham operation group (Sham group), SAH group, SAH+ CTX group and SAH+ CTX+ Nrf2 inhibitor group (SAH+ CTX+ ML385 group) according to the random number table with 12 rats in each group.Seven days before modeling, rats in SAH+ CTX+ ML385 group were injected intraperitoneally with ML385 (30 mg · kg -1) once a day for consecutive 7 days.And 5 days before modeling, rats in SAH+ CTX group and SAH+ CTX+ ML385 group were treated with CTX(200 mg · kg -1) by intraperitoneal injection once a day for five consecutive days.Rats in Sham group and SAH group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution.After 24 hours of modeling, the neurological function score and brain tissue water content of rats in each group were measured.HE staining was used to observe the morphology of neurons in CA1 and CA3 regions of hippocampus.Prussian blue staining was used to observe the iron deposition in cerebral cortex.Spectrophotometer was used to determine the iron content, malonic dialdehyde(MDA) content, glutathione(GSH) content and GPX4 activity in cerebral cortex.Western blot was used to detect the expression levels of Nrf2 and GPX4 proteins in cerebral cortex.SPSS 23.0 was used for statistical analysis.One-way ANOVA was used to compare the mean of multiple groups of samples, and Dunnett- t test was used for further pairwise comparison between groups. Results:There was a statistically significant difference in the neurological function scores of rats in the four groups 24 hours after SAH ( F=48.40, P<0.001). The neurological function score of rats in the SAH group 24 hours after SAH was significantly lower than those in Sham group and SAH+ CTX group (both P<0.05). The brain water content of rats in the four groups 24 h after SAH was statistically significant ( F=49.61, P<0.001). The brain water content of rats in the SAH group 24 h after SAH was significantly higher than that in Sham group and SAH+ CTX group(both P<0.05). There was statistically significant differences in the number of neuronal necrosis in CA1 and CA3 regions of hippocampus in the four groups 24 hours after SAH ( F=17.44, 246.50, both P<0.001). The numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH group were significantly higher than those in Sham group and SAH+ CTX group, and the numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH+ CTX+ ML385 group were significantly higher than those in SAH+ CTX group (all P<0.05). Twenty-four hours after SAH, the amount of iron deposited in the cerebral cortex of rats in the four groups was statistically significant ( F=2 363.0, P<0.001). The iron deposition in the cerebral cortex of rats in the SAH group was significantly higher than those in Sham group and SAH+ CTX group (both P<0.05). There were significant differences in iron content, MDA content, GSH content and GPX4 activity in the cerebral cortex of the four groups 24 h after SAH( F=2 380.0, 1 322.0, 789.1, 815.5, all P<0.001). The content of iron and MDA in the cerebral cortex of rats in SAH group were significantly higher than those in Sham group, while the content of GSH and the activity of GPX4 were significantly lower than those in Sham group (all P<0.05). The content of iron and MDA in the cerebral cortex of rats in SAH+ CTX group were lower than those in SAH group, and the content of GSH and the activity of GPX4 were higher than those in SAH group (all P<0.05). At 24 h after SAH, the expression levels of Nrf2 and GPX4 protein in the cerebral cortex of the four groups were statistically significant ( F=888.7, 1 556.0, both P<0.001). The protein expression levels of Nrf2 (0.382±0.014) and GPX4 (0.329±0.019) in the cerebral cortex in SAH group were lower than those in Sham group ((0.746±0.009), (0.953±0.009)) (both P<0.05). The expression levels of Nrf2 (0.631±0.006) and GPX4 (0.833±0.008) protein in the cerebral cortex in the SAH+ CTX group were significantly higher than those in the SAH group (both P<0.05). The expression levels of Nrf2 (0.427±0.009) and GPX4 (0.525±0.011) protein in the cerebral cortex in SAH+ CTX+ ML385 group were significantly lower than those in SAH+ CTX group (both P<0.05). Conclusion:Ceftriaxone may inhibit ferroptosis during EBI in SAH rats by regulating Nrf2/GPX4 signal axis.

Noninvasive Tracking of Every Individual in Unmarked Mouse Groups Using Multi-Camera Fusion and Deep Learning / 神经科学通报·英文版

Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.

Preparation quality control and clinical application observation of pooled platelets with leukocytes reduced / 中国输血杂志

【Objective】 To investigate the preparation quality and clinical application effect of pooled platelets with leukocytes reduced. 【Methods】 The quality and clinical effect of the buffy-coated method prepared pooled platelets leukocytes reduced (experimental group, n=40) and apheresis platelets leukocytes reduced (control group, n=40) were compared. 【Results】 The platelet volume (mL), platelet count (×1011), red blood cell contamination (×108) and residual white blood cell (×106) of the experimental group and control group were 278.90±7.92 vs 276.52±8.01, 2.66±0.09 vs 2.66±0.83, 0.54±0.42 vs 0.83±0.84, 0.29±0.54 vs 0.27±0.51, respectively, with no significant difference. The results of bacterial culture were negative, all met the requirements of relevant national standards. In addition, the CCI (×103, 24 h) and PPR (%) were 15.11±9.86 vs 14.61±12.55 and 54.23±18.70 vs 61.41±19.09 respectively, with no significant difference, indicating a certain degree of therapeutic effect. 【Conclusion】 The quality and clinical therapeutic effect of pooled platelets leukocytes reduced were consistent with that of apheresis platelets leukocytes reduced.

Research progress of new drug delivery system of gambogic acid / 中国药房

Gambogic acid is the main active component of Garcinia hanburyi Hook. f. ，which can inhibit the growth of a variety of tumor cells. However ，its low solubility ，short half-life and poor stability limit its clinical application to a certain extent. In order to improve the above shortcomings and improve the bioavailability of gambogic acid ，many studies have used covalent binding and physical encapsulation methods to obtain a new gambogic acid delivery system with targeting ，high permeability ，stability， biocompatibility，in vivo long circulation and other properties ，such as polymer prodrug delivery system ，anoxic prodrug delivery system，magnetic field responsive prodrug delivery system ，multi environment sensitive prodrug delivery system ，bionic nano drug delivery system. This paper reviews the new drug delivery system and its characteristics of gambogic acid. The results show that the design of drug carrier has greatly improved the defects of gambogic acid ，and the introduction of more responsive groups into gambogic acid drug carrier may make it achieve better antitumor effect.

Effects and mechanisms of melatonin combined with enriched environment on learning and memory ability of SAMP8 mice / 中华行为医学与脑科学杂志

Objective:To explore the effects and possible mechanisms of melatonin combined with enriched environment on the learning and memory ability of senescence-accelerated mouse prone 8(SAMP8).Methods:Forty-eight SAMP8 male mice aged 4 months were randomly divided into model group, enriched environment group, melatonin group and melatonin combined with enriched environment group (combined intervention group) by random number table method, with 12 mice in each group. Mice in the melatonin group and combined intervention group were subcutaneously injected with melatonin at a dose of 8 mg·kg -1·d -1, and the mice in the model group and the enriched environment group were given the same amount of normal saline instead.The mice in model group and melatonin group were raised in a standard environment, and the mice in enriched environment group and combined intervention group were raised in an enriched environment.The intervention lasted 28 days. The aging degree of mice was scored before and 28 days after the intervention. Morris water maze test was used to detect the learning and memory ability of mice. Nissl staining and TUNEL staining were used to observe the Nissl staining positive cells and apoptotic cells in the CA1 area of hippocampus.ELISA was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus of mice. Western blot was used to detect the levels of amyloid β-protein (Aβ) 1-42, microtubule-associated protein tau (tau) phosphorylated at threonine (Thr) 205 (Tau pT205), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) p65 protein in the hippocampus of mice. qRT-PCR was used to detect the levels of TLR4, NF-κB p65 mRNA in the hippocampus of mice. SPSS 22. 0 statistical software was used for repeated measure ANOVA, one-way ANOVA and LSD test. Results:(1) Aging score: after intervention, the aging scores of mice in the four groups were significantly different ( F=120.601, P<0.01). The aging scores of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group (all P<0.05), while the aging score of mice in the combined intervention group was significantly lower than those in the enriched environment group and melatonin group (both P<0.05). (2) The results of the location navigation experiment showed that the time × group interaction effect of the escape latencies of mice in the four groups were significant ( F=30.524, P<0.001). From the 2nd to 4th day, the escape latencies of mice in the enriched environment group, melatonin group and combined intervention group were all lower than that in the model group (all P<0.05). The results of the space exploration experiment showed that the residence time in the target quadrant and the number of platform crossings of mice in the four groups were significantly different ( F=291.328, 113.482, both P<0.01). The residence time in the target quadrant ((29.45±1.70)s, (32.44±1.55)s, (37.48±0.84) s) and the number of platform crossings ((6.44±0.61) times, (7.16±0.70) times, (12.60±1.23) times) of mice in the enriched environment group, melatonin group and combined intervention group were higher than those in the model group ((15.07±1.28) s, (4.10±0.61) times), while the residence time in the target quadrant and the number of platform crossings of mice in the enriched environment group and the melatonin group were significantly lower than those in the combined intervention group (all P<0.05). (3) Nissl and TUNEL staining showed that the number of Nissl positive neurons in the hippocampal CA1 region of mice in the four groups were significantly different ( F=809.264, P<0.01), and the number of apoptotic cells in the hippocampal CA1 region were also significantly different ( F=1 060.583, P<0.01). The number of Nissl stained positive neurons in the hippocampal CA1 region of mice in the combined intervention group was more than those in the model group, enriched environment group, and melatonin group (all P<0.05), and the number of apoptotic cells were less than those in the model group, enriched environment group, and melatonin group (all P<0.05). (4) The results of ELISA assay showed that there were significantly different in the levels of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the four groups ( F=152.887, 63.506, 432.026, all P<0.01). The contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group(all P<0.05). Among them, the contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (5) Western blot analysis showed that there were significantly different in the protein expression levels of Aβ1~42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the four groups ( F=122.349, 98.934, 201.635, 116.553, all P<0.01). The protein expression levels of Aβ1-42, tau pT205, TLR4, and NF-κB p65 in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group.Among them, the protein expression levels of Aβ1-42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (6) qRT-PCR showed that the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the four groups were significantly different ( F=42.913, 102.446, both P<0.01). The mRNA expression levels of TLR4 ((0.63±0.05), (0.55±0.04), (0.42±0.03)) and NF-κB p65 ((0.98±0.06), (0.82±0.04), (0.72±0.04)) in the hippocampus of mice in the enriched environment group, melatonin group and combined intervention group were lower than those in the model group ((0.74±0.07), (1.20±0.05)) (all P<0.05). Among them, the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). Conclusion:Melatonin combined with enriched environment can improve the learning and memory ability and neuroinflammatory response of SAMP8 mice, and its mechanism may be related with the down-regulation of TLR4/NF-κB p65 signaling pathway.

Experimental study and clinical significance of intravascular angiography in vivo / 中华骨科杂志

Objective:To study the method of intravascular angiography in vivo, analyze the clinical significance, and supply the basis of diagnosis and treatment of related orthopaedic diseases.Methods:The development was realized by improving the developer to increase the local concentration. Based on the study of Lijianmin-Chengkun Complexes and using the theory of magnetic microspheres, Fe 3O 4 magnetic microspheres with amino (negatively charged) shell are used to adsorb the aggregated ionic developer meglumine diatrizoate (positively charged diatrizoate). That is, by improving the method of developer, the magnetic microspheres can carry the developer to make new nanoparticles magnetic imaging composite particles. Under the action of external magnetic field, the magnetic imaging composite particles brought by blood circulation continue to stay and gather in the blood vessels in the magnetic field area, and the developer carried by the magnetic microspheres in the blood vessels in the magnetic field area is concentrated to reach the imaging concentration, so as to realize in vivo intravascular vascular imaging. By adjusting the ratio of the two reagents, the charge can be neutralized and condensed into small groups to improve the development efficiency. Thus, the electron microscope experiment, CT in vivo experiment, rabbit imaging experiment, experimental rabbit tissue picture confirmation, CT in vivo human body (the author is a volunteer) imaging experiment were carried out step by step. Results:Electron microscope experiment: meglumine diatrizoate, scanning electron microscope, the particle diameter is about 20 nm. Scanning electron microscope showed that the diameter of the magnetic microspheres was about 100 nm and the distribution was uniform. After the two reagents are mixed in a certain proportion, the neutralizing charge condenses into small groups, but it still has magnetohydrodynamic properties and strong paramagnetism. In vivo rabbit imaging experiment: the ideal intraosseous vascular imaging of the proximal tibia was captured. The tissue pictures of experimental rabbits confirmed that the distribution of Fe 3O 4 was obviously visible in the blood vessels in the proximal tibia on the side with magnetic field, but not on the side without magnetic field. In vivo human imaging experiment: the ideal intraosseous vascular imaging of the proximal fibula was captured. Conclusion:Through the preparation of new reagent of magnetic imaging composite particles (magnetic microspheres + meglumine diatrizoate), the concentration of in vivo bone developer can be achieved under the action of external magnetic field, and the in vivo external diameter ≥ 0.5mm can be achieved under CT thin-layer scanning.

Advances of salt stress-responsive transcription factors in plants / 生物工程学报

Salt stress may cause primary osmotic stress and ion toxicity, as well as secondary oxidative stress and nutritional stress in plants, which hampers the agricultural production. Salt stress-responsive transcription factors can mitigate the damage of salt stress to plants through regulating the expression of downstream target genes. Based on the soil salinization and its damage to plants, and the central regulatory role of transcription factors in the plant salt stress-responsive signal transduction network, this review summarized the salt stress-responsive signal transduction pathways that the transcription factors are involved, and the application of salt stress-responsive transcription factors to enhance the salt tolerance of plants. We also reviewed the transcription factors-regulated complex downstream gene network which is formed by forming homo- or heterodimers between transcription factors and by forming complexes with regulatory proteins. This paper provides a theoretical basis for understanding the role of salt stress-responsive transcription factors in the salt stress regulatory network, which may facilitate the molecular breeding for improved stress resistance.

Preliminary investigation on the dissected methods of intraosseous vasculature and the clinical significances of intraosse-ous vascularity / 中华骨科杂志

Objective:The vasculature and canal were located using radiography after the fresh osseous specimens were decalcified, after which the anatomic investigation of intraosseous vasculature was conducted based on the orientation of the canals.Methods:To investigate the basic dissected methods for intraosseous vasculature and the related clinical significance. Methods The materials were obtained from seven fresh knee joint specimens from patients with amputation due to car accidents, nine fresh knee joint specimens from patients with amputation due to oncological radical surgery, and 44 knee joint specimens from 24 cadavers. Among them, 22 were males (55%) and 18 were females (45%), 28 were left knees (46.7%) and 32 were right knees (53.3%). 10 were aged from 16-90 years old (from 8 donors) and 50 were aged from 15-85 years old (from 32 donors). The tributaries of middle genicular vein which penetrate into the proximal tibial epiphysis and metaphysis via our previously discovered and denominated "foramen of tibial intercondylar eminence (FTIE)" were dissected as an example. After obtaining the fresh knee joint specimen, angiography was performed to observe the continuous extraosseous and intraosseous blood vessels. The first group of specimens with the removal of cortical bone was reserved in formalin solution at 4 °C for 7 d, sequentially immersed in Ethylene Diamine Tetraacetic Acid (EDTA), the decalcification agent, for 30 d with replacement for each two days. Based on the CT scanning and three-dimensional reconstruction, the orientation of bony canal which enclosed the vasculature was exposed to guide the anatomic incision. The exquisite dissection was achieved with the help of ophthalmological microsurgical instruments. The anatomical dissection were intuitively observed, compared with the angiographic images, and verified by histological examinations. The second group of samples was decalcified with strong acid as another strategy, and the comparison between different groups was conducted. To estimate the advantages and disadvantages of the two decalcification and dissection methods, and the distribution and universality of specific intraosseous vasculatures and canals, the methods can be utilized to dissect the diameter of the intraosseous vessels. Based on the anatomical study of intraosseous vasculature, the mechanisms including etiology, recurrence and spread of bone tumors and epiphyseal injuries were analyzed to improve the therapeutic regimen.Results:The intraosseous tributaries of middle genicular vein which penetrate into the tibial intercondylar eminence from the articular cavity were dissected, these vessels extended to the tibial metaphysis from epiphysis through the epiphyseal line or senescent physes. The diameter of the vessel entering the FTIE was 1.2 mm, and the intraosseous vessels divided into several tinier tributaries with the diameter of 0.3 mm to cross the epiphyseal line or closed physeal plate and differentiated into capillaries in the distal regions, therefore was difficult to dissect directly. The histological examinations confirmed the authenticity of intraosseous vessels. Compared with the samples decalcified with strong acid, the blood vessels were obviously dissolved, and only a few residual epithelial cells were observed under the light microscope. Based on the anatomical study of intraosseous vessels, the treatment protocols for some related bone tumors and epiphyseal injuries were modified and satisfactory results were achieved.Conclusion:The methods can realize the ideal direct dissection for the intraosseous blood vessels with the outer diameter greater than or equal to 0.3 mm.

Clinical study on individual protection after 125I seed implantation for abdominal and pelvic tumors / 中华放射医学与防护杂志

Objective:To study the radiation dose rate and effective dose in ambient environment due to 125I seed implantation in the treatment of the patients suffering abdominal and pelvic tumors, so as to provide reference for occupational protection of different groups. Methods:Within 24 hours after operation, the radiation dose rate to 42 patients with abdominal and pelvic tumor with 125I seed implantation was monitored by using pocket dosimeter. The relationships between the total activity in the implanted particles and the measured dose rate, as well as between the implanted depth and the dose rate under the standard activity, were obtained by curve fitting. According to the formula, the relationship between the dose rate and the warning time was calculated. Results:The dose rates at 30 cm, 50 cm and 100 cm of vertical particle implantation site were (6.92±2.87), (4.10±1.62) and (1.30±0.48) μSv/h, respectively ( χ2=73.71, P<0.05). The dose rates on the left and right sides were (0.378±0.156) and (0.384±0.153) μSv/h at 30 cm, (0.170±0.089) and (0.17±0.086) μSv/h at 50 cm, (0.039 ±0.014) and (0.043±0.017) μSv/h at 100 cm, respectively ( χ2=76.19, 76.33, P<0.05). There was a linear relationship between the dose rate at the vertical particle implantation site and the total activity in the implanted particles, and between the dose rate and the implantation depth under the standard activity. The relationship between the warning time and the dose rate to adults in the same bed, co-workers, minors in the same bed and pregnant women were as follows: t ( d)=-106.616+ 83.779ln D( t), t ( d)=26.556+ 85.933ln D ( t), t( d)=3.088+ 85.017ln D( t). Conclusions:After 125I seed implantation, the radiation dose in the ambient environment is low, ensuring the radiation safety; and the measured dose rate decreases with the decrease in the total activity in the implanted particle and the increase in the implantation depth; at the same time, the warning time for different groups is calculated according to the measured dose rate or the total activity in the implanted particle and the depth of the implanted particle, so as to carry out individualized protection.

Protective effect of baicalein on injured PC12 cell induced by Aβ and its mechanism / 国际中医中药杂志

Objective:To investigate the protective effect of baicalein on injured PC12 cell induced by Aβ and explore its mechanism.Methods:The method of MTT was used to detect the cell activity of each group and screened the concentration of baicalein. The PC12 cells were randomly divided into the blank group, the Aβ group, the baicalin group and the estradiol group. 24 hours after inoculation, baicalein group was intervened with 1×10 -6 mol/L baicalein solution, and estradiol group was intervened with 1×10 -5 mol/L estradiol solution. Two hours later, except the blank group, the other groups were added with 1.5×10 -4 mol/L Aβ to make the model. MTT assay was used to detect the cell viability of each group after 24 hours of cultivation. Then used oxidation kit to detect the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and lactate dehydrogenase (LDH) in each group. And the level of caspase-3 mRNA was detected by Real-time Quantitative PCR (RT-PCR). Then the Western blot method was used to detect the expressions of p-PI3K, p-AKT and caspase-3. Results:Compared with the Aβ group, the PC12 cell viability [(96.348 ± 0.571)%, (97.183 ± 0.714)% vs. (86.922 ± 0.429)%] in the baicalin group and the estradiol group significantly increased( P<0.01). The activities of SOD [(54.31 ± 1.34) U/mgprot, (57.38 ± 2.25) U/mgprot vs. (36.18 ± 2.24) U/mgprot] and GSH-PX [(4.46 ± 0.23) U/mgprot, (4.72 ± 0.31) U/mgprot vs. (2.05 ± 0.37) U/mgprot] significantly increased, and the level of LDH [(85.43 ± 0.92) nmol/ml, (82.46 ± 0.27) nmol/ml vs. (99.17 ± 0.52) nmol/ml] significantly decreased ( P<0.01). The expression of caspase-3 mRNA (2.24 ± 0.64, 2.33 ± 0.75 vs. 3.46 ± 0.46) and p-PI3K (0.46 ± 0.03, 0.44 ± 0.06 vs. 0.66 ± 0.09), p-AKT (0.43 ± 0.05, 0.41 ± 0.02 vs. 0.58 ± 0.03), caspase-3 (0.61 ± 0.03, 0.56 ± 0.53 vs. 0.92 ± 0.07) protein significantly decreased ( P<0.01). Conclusion:Baicalein could slow down cell apoptosis and oxidative reaction, reduce the damage of Aβ to PC12 cells by inhibiting the expression of PI3K/AKT pathway.

SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry

The recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.

Feasibility Study of the Low-Cost Motion Tracking System for Assessing Endoscope Holding Skills.

BACKGROUND: The ability to hold an endoscope is an important skill for surgeons and assistants performing endoscopic neurosurgery. Motion tracking can provide an objective assessment for surgical skills and may aid in endoscopic neurosurgery. We developed a cost-effective system to study the feasibility of objectively distinguishing performance levels for operating an endoscope. METHODS: The study was divided into 2 parts. First, a video motion tracking analysis tool was built based on a printed mark and free software (Kinovea 0.8.15). Second, the tool was used to distinguish the holding endoscope performance of the robotic arm by experts (surgeon, n = 3) and novice users (residents, n = 6) under both 0' and 30' endoscopes. RESULTS: Through the printed mark and free software, we successfully built a system for video motion tracking. The data analysis showed that for both 0' and 30' endoscopes, the experts had a shorter total distance and depth, smaller average speed and maximum acceleration, and a fewer number of extreme accelerations than their novice counterparts. Compared with experts and residents, the fixed arm had better results. CONCLUSIONS: The simple low-cost video motion tracking system can provide an objective assessment of an endoscope holding skill, which allows for discrimination between an expert and a novice, and can be used by clinical neurosurgeons to select a qualified assistant.

A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.

Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing

COVID-19, caused by SARS-CoV-2, has recently affected over 300,000 people and killed more than 10,000. The manner in which the key immune cell subsets change and their states during the course of COVID-19 remain unclear. Here, we applied single-cell technology to comprehensively characterize transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19. Compared with healthy controls, in patients in the early recovery stage (ERS) of COVID-19, T cells decreased remarkably, whereas monocytes increased. A detailed analysis of the monocytes revealed that there was an increased ratio of classical CD14++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1B+ monocytes in the ERS. CD4+ and CD8+ T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naive B cells decreased. Our study identified several novel B cell-receptor (BCR) changes, such as IGHV3-23 and IGHV3-7, and confirmed isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity. Furthermore, integrated analysis predicted that IL-1{beta} and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2 and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting that COVID-19 patients are still vulnerable after hospital discharge. Our identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19. Highlights- The immune response was sustained for more than 7 days in the early recovery stage of COVID-19, suggesting that COVID-19 patients are still vulnerable after hospital discharge. - Single-cell analysis revealed a predominant subset of CD14++ IL1{beta}+ monocytes in patients in the ERS of COVID-19. - Newly identified virus-specific B cell-receptor changes, such as IGHV3-23, IGHV3-7, IGHV3-15, IGHV3-30, and IGKV3-11, could be helpful in the development of vaccines and antibodies against SARS-CoV-2. - IL-1{beta} and M-CSF were discovered as novel mediators of inflammatory cytokine storm, and TNFSF13, IL-2, IL-4, and IL-18 may be beneficial for recovery.

Novel Cost-Effective Tubular Port Based on Glove and Syringe for Endoscopic Surgery of Intracerebral Hematomas.

BACKGROUND: Intracerebral hematomas (ICH) is a common disease in the developing countries, and minimally invasive transportal resection of ICH is a widely accepted surgical technique. Many port systems are available, but most are disposable and expensive. We present a safe and cost-effective glove-syringe substitute for endoscopic hematoma evacuation, suitable for developing countries such as China. METHODS: A port substitute of different sizes and lengths was constructed using sterile gloves and syringes, commonly found in a surgical environment. RESULTS: We successfully performed endoscopic hematoma removal in 7 patients including 1 cerebellar hemorrhage case and the remaining 6 supratentorial basal ganglia cases (1 patient taking oral aspirin). Bipolar electrocoagulation was used to control bleeding from the ruptured blood vessels. There were no postsurgical complications. CONCLUSIONS: The glove-syringe port is a convenient, safe, and cost-effective tubular port system for endoscopic surgery of ICH. Such ports can be used as substitutes when commercial sleeves are unavailable, especially in rural areas and developing countries.

The relationship between the recurrence rate of aggressive tumors and the foramina around the knee joint / 中华骨科杂志

Objective:To introduce the discovery and nomenclature of the intercondylar foramen of femur (IFF) and foramen of tibial intercondylar eminence (FTIE) and research the close relationship between the high recurrence rate of aggressive tumors around the knee joint and the foramina around the knee joint.Methods:①Radiographic observation and measurement: 3D reconstruction of CT scan of 200 patients in our hospital were used to obverse the common feature、position and measure of Inter-condylar foramen of femur and Foramen of tibial intercondylar eminence. ②Anatomical and histological observation: To proof the existence of IFF and FTIE through the anatomy of 15 cases of car accidents or tumor amputations and 60 cases of autopsy. Then the specific location, the surrounding structure, the proximal coverage, the contents, the apical construction, the wall and the bottom tissues of the IFF and FTIE were studied and analyzed. ③Histological and pathological observation of tumor anatomy: Through the study of the distal femur and tibia malignant tumor tissues(including primary bone tumors and metastatic tumors), we observed the relationship between the foraminal structures and the tumor, judged the situation of concealed transmission and two-way spread through the foramina, and analyzed the relationship between tumor recurrence and foraminal structures. ④The synovial membrane of foramina, especially in cases where the synovium was suspected to be involved by the lesions judged by the radiography was analyzed to observe whether the synovium was infiltrated by the tumor.Results:IFF and FTIE were the inherent physical structure of the human. Their physiological function was the vascular foramina that lead the branches of arteria media genus into the Intercondylar fossa of femur and tibial intercondylar eminence. Their opening was separated with the joint cavity by the synovial tissues, so IFF and FTIE were isolated with joint cavity by the synovial tissues、meniscus and cruciate ligaments. After invading the IFF and FTIE, the aggressive tumors did not break into the joint cavity immediately, but conceal in the foramina and invade the synovium with specific biological behavior with the sequence: reactive edema, hyperplasia, degeneration, calcification, hyaline degeneration (infiltration in some cases), synovial rupture, and then tumor invasion of the articular cavity. Usually, tumors or recurrence has been observed before synovial rupture. We also observed the tendency of tumors to spread along the arteria media genus to the popliteal vessels, peripheral soft tissues and lymphatic vessels with typical radiographic performance like popliteal lymphadenectasis. Color nodules and tumors in other parts could also invade or metastasize into bone through these foramina.Conclusions:IFF and FTIE are foramina nutricium of arteria media genus. They are the inherent physical structure of the human. The foramina play an important role in the spread, concealment and recurrence of peripheralkneeaggressive tumor.

Leriche syndrome missed diagnosis: a case report / 中华骨科杂志

The study showed a case of missed diagnosis of Leriche syndrome.Patients with intermittent claudication were diagnosed as lumbar spinal stenosis by local hospital with lumbar MRI.When conservative treatment was ineffective,the patients were treated in our spine clinic.However,the lumbar MRI showed no significant stenosis,and arteriovenous ultrasound also showed no abnormality.Vascular surgeons believed that patient's symptoms had little correlation with vascular lesions.After careful reading of lumbar spine MRI,we found that the signal intensity of abdominal aorta increased unevenly below L2 vertebral level.CTA examination of abdominal aorta revealed sclerosis of abdominal aorta and common iliac artery,stenosis and occlusion of abdominal aorta and common iliac artery lumen below the level of renal artery orifice.The patient was finally diagnosed as Leriche syndrome.

Effects of modified acidic fibroblast growth factor mediated by nanoliposomes combined with ultrasound-targeted microbubble destruction on left ventricular systolic function in diabetic rats / 中华超声影像学杂志

Objective:To investigate the effects of modified acidic fibroblast growth factor (MaFGF) mediated by nanoliposomes combined with ultrasound-targeted microbubble destruction (UTMD) on left ventricular systolic function in early diabetes mellitus(DM) rats.Methods:The nanoliposomes containing MaFGF(MaFGF-nlip) were prepared by reverse phase evaporation method. Among 60 male Sprague Dawley (SD) rats, 50 rats were randomly selected and were induced to be DM models by streptozotocin(STZ) through intraperitoneal injecting, the other 10 rats as control group. Then DM rats were randomly divided into 4 groups: DM model group, MaFGF solution group, MaFGF-nlip group and MaFGF-nlip+ UTMD group. After the successful induction of DM model, the intervention was performed twice a week.After 12 weeks of intervention, all rats underwent conventional echocardiography and velocity vector imaging (VVI). Left ventricular ejection fraction (LVEF) and left ventricular fraction shortening(LVFS) were measured by conventional echocardiography. The mean peak systolic radial velocity (Vs), radial strain (Sr) and radial strain rate (SRr) of six walls at the papillary muscle level were measured in left ventricular short-axis view by VVI. At last, myocardial tissue of all rats were stained with Sirius red to evaluate myocardial interstitial fibrosis. The level of myocardial apoptosis was evaluated by TUNEL staining, and the changes of myocardial ultrastructure were observed by transmission electron microscopy.Results:The prepared MaFGF-nlip were more rounded, evenly dispersed, and of good stability and high encapsulation efficiency. Twelve weeks later after intervention, LVEF, LVFS, Vs, Sr and SRr in the DM model group were significantly lower than those in the control group (all P<0.05). LVEF, LVFS, Vs, Sr and SRr in the MaFGF-nlip+ UTMD group were significantly higher than those of the DM model group and other intervention groups (all P<0.05). The results of Sirius red staining and Tunel staining showed that CVF and AI in the DM model group were significantly higher than those in the control group (all P<0.05). For MaFGF-nlip+ UTMD group, CVF and AI were significantly decreased compared with the DM model group and other intervention groups(all P<0.05). According to the results of transmission electron microscopy, compared with the DM model group, the improvement of myocardial ultrastructure was the most obvious in the MaFGF-nlip+ UTMD group. Conclusions:MaFGF delivered by using nanoliposomes combined with UTMD can improve the left ventricular systolic function in diabetic rats by inhibiting the myocardium cardiac fibrosis and reducing the cardiomyocyte apoptosis.

Leriche syndrome missed diagnosis: a case report / 中华骨科杂志

The study showed a case of missed diagnosis of Leriche syndrome. Patients with intermittent claudication were diagnosed as lumbar spinal stenosis by local hospital with lumbar MRI. When conservative treatment was ineffective, the patients were treated in our spine clinic. However, the lumbar MRI showed no significant stenosis, and arteriovenous ultrasound also showed no abnormality. Vascular surgeons believed that patient’s symptoms had little correlation with vascular lesions. After careful reading of lumbar spine MRI, we found that the signal intensity of abdominal aorta increased unevenly below L2 vertebral level. CTA examination of abdominal aorta revealed sclerosis of abdominal aorta and common iliac artery, stenosis and occlusion of abdominal aorta and common iliac artery lumen below the level of renal artery orifice. The patient was finally diagnosed as Leriche syndrome.