Dynamic changes in cytoskeletal elements following acute cerebral ischemia and reperfusion in rats / 中国药理学通报

Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Effect of alisol A on cerebral ischemia reperfusion injury by protecting blood brain barrier and its mechanism / 中国药理学通报

Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol

GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Clinical effect of cross positioning method for correcting low and moderate astigmatism during small incision lenticule extraction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical outcomes of using the cross-positioning method for correcting low and moderate astigmatism during small incision lenticule extraction(SMILE)surgery with Alpins vector analysis.METHODS: A total of 50 patients(81 eyes)with low and moderate astigmatism with the rule ≤1.50 D who underwent SMILE surgery at the laser myopia treatment center of Xi'an No.1 Hospital from May 2022 to November 2022 were included in the prospective randomized controlled study, and they were divided into two groups according to the random table, with 25 case(41 eyes)in cross-positioning group and 25 cases(40 eyes)in control group. In the cross-positioning group, the patients' head position was adjusted based on the cross intersection lines before the standard SMILE procedure, aligning the lateral canthi with the horizontal line and the midpoint of the eyebrows and the nose bridge with the vertical line. Postoperative visual acuity and refractive results at 3 mo were observed in both groups, and astigmatic changes were analyzed and evaluated using the Alpins vector analysis method.RESULTS: During the follow-up period, 6 cases(11 eyes)in the cross-positioning group were lost to follow-up, while in the control group, 8 cases(14 eyes)were lost to follow-up, with 19 cases(30 eyes)and 17 cases(26 eyes)finally included in the cross-positioning group and the control group, respectively. At 3 mo postoperatively, the uncorrected visual acuity(UCVA)of both groups' operated eyes was ≥1.0, and no serious complications occurred, with no significant differences in UCVA, best corrected visual acuity(BCVA), spherical power, and spherical equivalent between the cross-positioning group and the control group(all P&#x0026;#x003E;0.05). The cylindrical power in the cross-positioning group was 0.00(0.00, 0.00)D, which was lower than -0.13(-0.50, 0.00)D in the control group(P=0.01). The vector analysis results showed that the difference vector(DV)in the cross-positioning group was lower than that in the control group [0.00(0.00, 0.00)vs 0.13(0.00, 0.50), P=0.01], and the index of success(IOS)was better than that of the control group [0.00(0.00, 0.00)vs 0.18(0.00, 0.77), P&#x0026;#x003C;0.01]. At 3 mo postoperatively, 26(87%)and 15(58%)eyes in the cross-positioning group and control groups achieved an angle of error(AE)within ±5°, respectively.CONCLUSION: The cross positioning method was used to calibrate the patients' head position during SMILE surgery, which reduced the axial position error and improved the accuracy of SMILE in correcting low and moderate astigmatism.

Corrective effect of femtosecond laser assisted laser in situ keratomileusis Xtra on patients with moderate to high myopia after 2a postoperatively / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate corrective effect and stability of corneal morphology in patients with moderate to high myopia after 2a treatment of femtosecond laser assisted laser in situ keratomileusis(FS-LASIK)Xtra.METHODS:Retrospective case-control study. A total of 30 cases(58 eyes)Patients with moderate to high myopia combined with astigmatism who planned to undergo refractive surgery in our hospital from August 2019 to August 2020 were included, and different types of surgery were performed respectively based on the relevant index of keratoconus screening in the preoperative corneal topography. They were divided into FS-LASIK group and Xtra group, with 15 cases(29 eyes)in each group. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE)and the corneal curvature of the anterior and posterior surfaces of different diameters(3, 5 and 7 mm)measured by Sirius three-dimensional corneal topography were observed preoperatively and 3 mo, 1 and 2 a postoperatively.RESULTS: The UCVA of the two groups of patients at different time points after surgery was significantly increased compared with preoperatively(both P&#x0026;#x003C;0.01), and there was no difference in UCVA and SE between the two groups(P&#x0026;#x003E;0.05). After 2 a postoperatively, residual astigmatism was -0.25-0 D in 25 eyes(86%)of the FS-LASIK Xtra group and 24 eyes(83%)of the FS-LASIK group. The actual corrected SE and expected corrected SE of both groups were positively correlated(both P&#x0026;#x003C;0.05). There were differences in corneal curvature on the surface of different diameter areas(3, 5, and 7 mm)between the two groups at 3 mo, 1, and 2 a postoperatively compared with preoperatively. After 1 and 2 a postoperatively, the corneal posterior surface curvature of the FS-LASIK Xtra group with corneal diameter of 3 and 5 mm was higher than that of the FS-LASIK group(P&#x0026;#x003C;0.05).CONCLUSIONS:FS-LASIK Xtra has good safety, efficacy and predictability in correcting patients with moderate to high myopia.

Follow-up and prognostic study of infants with positional plagiocephaly / 中国当代儿科杂志

OBJECTIVES@#To study the effects of infantile positional plagiocephaly on the growth and neural development.@*METHODS@#A retrospective study was conducted on the medical data of 467 children who underwent craniographic examination and were followed up to 3 years of age in Peking University Third Hospital from June 2018 to May 2022. They were divided into four groups: mild positional plagiocephaly (n=108), moderate positional plagiocephaly (n=49), severe positional plagiocephaly (n=12), and normal cranial shape (n=298). The general information of the four groups and the weight, length, head circumference, visual acuity screening results, hearing test results, and the scores of Pediatric Neuropsychological Developmental Scales/Gesell Developmental Schedules of the four groups from 6 to 36 months old were compared.@*RESULTS@#The rates of adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping posture in the mild, moderate, and severe positional plagiocephaly groups were higher than the normal cranial group (P<0.05). There was no significant difference in weight, length, and head circumference among the four groups at 6, 12, 24 and 36 months of age (P>0.05). The incidence rate of abnormal vision in the severe positional plagiocephaly group was higher than that in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups at 24 and 36 months of age (P<0.05). The scores of the Pediatric Neuropsychological Developmental Scales at 12 and 24 months of age and the scores of the Gesell Developmental Schedules at 36 months of age in the severe positional plagiocephaly group were lower than those in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups, but the difference was not statistically significant (P>0.05).@*CONCLUSIONS@#Adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping position may be associated with infantile positional plagiocephaly. Mild or moderate positional plagiocephaly has no significant impact on the growth and neural development of children. Severe positional plagiocephaly have adverse effects on the visual acuity. However, it is not considered that severe positional plagiocephaly can affect the neurological development.

Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis / 亚洲男科学杂志(英文版)

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

Multiple portions enteral nutrition and chyme reinfusion of a blunt bowel injury patient with hyperbilirubinemia undergoing open abdomen: A case report / 中华创伤杂志(英文版)

Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.

Resveratrol improves cognitive function in severely burned rats by inhibiting hippocampal NF-κB/JNK pathway / 细胞与分子免疫学杂志

Objective To investigate the protective effect of resveratrol (RSV) on improving cognitive function in severely burned rats and its possible mechanism. Methods 18 male SD rats aged 18-20 months were randomly divided into 3 groups: control group, model group and RSV group, with 6 rats in each group. After successful modeling, the rats in RSV group were gavaged once daily with RSV (20 mg/kg). Meanwhile, the rats in control group and model group were gavaged once daily with an equal volume of sodium chloride solution. After 4 weeks, the cognitive function of all rats was estimated by Step-down Test. The concentration of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) protein in serum of rats were detected by ELISA. The expression of IL-6, TNF-α mRNA and protein were estimated by real-time PCR and Western blotting. The apoptosis of hippocampal neurons was tested by terminal deoxynuclectidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The expression of nuclear transcription factor-κB (NF-κB)/c-Jun N-terminal kinase (JNK) pathway-related proteins in hippocampus were assessed by Western blotting. Results Compared with the rats in model group, rats in RSV group exhibited improved cognitive function. Consistently, the rats in RSV group had a reduced concentration of TNF-α and IL-6 in serum, decreased mRNA and protein expressions of TNF-α and IL-6 in hippocampus, and decreased apoptosis rate and relative expression of p-NF-κB p65/NF-κB p65 and p-JNK/JNK in hippocampal neurons. Conclusion RSV alleviates inflammatory response and hippocampal neuronal apoptosis by inhibiting NF-κB/JNK pathway, thereby improving cognitive function in severely burned rats.

Multivariate correlation analysis of T1S and C7S / 中国骨伤

OBJECTIVE@#To determine whether C7 angles (C7 slope, C7S) could replace T1 angles (T1 slope, T1S) by correlation analysis of T1S and C7S.@*METHODS@#A total of 442 patients from July 2015 to July 2020 in outpatient and inpatient department were enrolled retrospectively, and 259 patients who could identify the upper endplate of T1 were screened out . Of them, there were 145 males and 114 females, aged from 20 to 83 years old with an average of (58.6±11.2) years, including 163 patients with cervical spine surgery and 96 non-surgical patients. Patients were stratified by sex, age, cervical kyphosis, cervical alignment imbalance, and cervical spine surgery. These 259 patients included 145 cases in the male group, 114 cases in the female group;76 cases in the youth group (<40 years old), 109 cases in the middle-aged group (40 to 60 years old), and 74 cases in the elderly group(>60 years old); 92 cases in the cervical kyphosis group, 167 cases in the non-kyphosis group;51 cases in the cervical sequence imbalance group, 208 cases in the non-imbalance group;163 cases in the cervical surgery group, 96 cases in the non-operation group. The correlations of C7S and T1S in various modalities groups were analyzed.@*RESULTS@#Of 442 patients, the recognition rate of upper endplate of T1 was 58.6%(259/442), and that of C7 was 90.7%. The mean T1S and C7S of the 259 patients were (24.5±8.0)° [(25.9±7.7)° in the male group and (23.7±6.9)° in the female group] and (20.8±7.3)° [(22.5±7.5)° in the male group and(19.7±5.8)° in the female group], respectively. The total correlation coefficient between C7S and T1S was r=0.89, R2=0.79, and the linear regression equation was T1S=0.91×C7S+4.35. In the above general information and the grouping of deformity factors, T1S was highly correlated with C7S(r value 0.85 to 0.92, P<0.05).@*CONCLUSION@#There is a high correlation between T1S and C7S in different factor groups. For cases where T1S cannot be measured, C7S can be used to provide guidance and reference for evaluating the sagittal balance of the spine, analyzing the condition, and formulating surgical plans.

Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats / 中国中药杂志

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.

Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

Genotyping Characteristics of Human Fecal Escherichia coli and Their Association with Multidrug Resistance in Miyun District, Beijing / 生物医学与环境科学（英文）

OBJECTIVE@#To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.@*METHODS@#Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).@*RESULTS@#This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).@*CONCLUSION@#We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Research on friction and wear behaviors of silicon-lithium spray coating on zirconia ceramics / 北京大学学报(医学版)

OBJECTIVE@#To study microstructure, friction and wear behaviors of silicon-lithium spray coating on the surface of zirconia ceramics and to preliminarily evaluate its esthetic so as to provide support and guidance for the clinical application.@*METHODS@#Zirconia ceramic specimens were randomly divided into three groups: coating group (two subgroups), polishing group (two subgroups), and glazing group (four subgroups), with 10 samples in each subgroup. The two subgroups of coating group were the zirconia ceramics with the untreated and preliminary polishing surfaces sprayed with silicon-lithium coating, respectively. The two subgroups of polishing group were preliminary polishing and fine polishing of zirconia ceramics, respectively. The four subgroups of glazing group were preliminarily polished zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively; and untreated zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively. The above 8 subgroups of zirconia ceramic specimens were used as friction pairs with 80 steatite ceramics for 50 000 chewing cycles under 50 N vertical load and artificial saliva lubrication using chewing simulation. Scanning electron microscope was used to observe the microstructure of the surface and section of the coating group, and the thickness of the coating and glazing were measured. The linear roughness of the coating and polishing groups was mea-sured using a laser confocal scanning microscope. Vickers hardness was measured using a microhardness tester and the esthetic of zirconia ceramic full crown sprayed with silicon-lithium coating was preliminarily evaluated. White light interferometer was used to measure the width, the maximum depth and the volume of the wear scars of each group, and the wear depth of steatite ceramics and wear rate of zirconia ceramic specimens were calculated. Kruskal-Wallis nonparametric test and Dunn's multiple comparisons test were used to analyze the wear depth of each group (α=0.05).@*RESULTS@#The microstructures of the silica-lithium spray coatings on the untreated and preliminarily polished zirconia ceramic surfaces showed the protruding defects, and the line roughness of coating group was larger than that of the polishing group. The median thickness of the silica-lithium spray coating on the preliminarily polished zirconia ceramic was 13.0 μm (interquartile range, IQR: 11.6, 17.9), while that of the silica-lithium spray coating on the untreated zirconia ceramic was 4.4 μm (IQR: 4.1, 4.7). The Vickers hardness and wear rate of the coating group were between the polishing group and the glazing group. The wear depths of the wear scars of steatite ceramics were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference between glazing and polishing groups (P < 0.05). With the increase of polishing procedure, the wear depth of steatite ceramics decreased in each subgroups. The orders of maximum depth and volume of wear scars of zirconia ceramic were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference in the maximum depth of wear scars between glazing and polishing groups (P < 0.05).@*CONCLUSION@#The silica-lithium spray coating on the zirconia ceramic, can be used as a new method for zirconia ceramic surface treatment, because it can increase the esthetic of zirconia ceramics compared with polishing and reduce the wear of steatite ceramics compared with glazing.

Better timing for HoLEP: a retrospective analysis of patients treated with HoLEP over a 10-year period with a 1-year follow-up / 亚洲男科学杂志(英文版)

The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People's Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8-18) and Group B (IPSS of 19-35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.

Intervention effect of injury control orthopedic strategy on fat embolism syndrome associated with long shaft fracture of lower limb / 中国骨伤

OBJECTIVE@#To observe the intervention effect of damage control orthopaedic(DCO) strategy on fat embolism syndrome(FES) associated with long shaft fracture of lower limbs.@*METHODS@#Retrospective analysis was made on the clinical data of 163 patients with FES associated with lower limb long shaft fractures admitted from January 2015 to May 2021. They were divided into two groups based on the time point of implementing DCO strategy in January 2018. Total of 92 patients were admitted from January 2015 to December 2017 as the control group, and other 71 patients were admitted from January 2018 to May 2021 as the intervention group. The hospital mortality, arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2) and oxygenation index (OI), hemoglobin (Hb), platelet count(PLT), Harris score of hip joint, HSS score of knee joint, AOFAS score of ankle joint, clinical efficacy and complications were observed and compared between two groups.@*RESULTS@#Total of 163 patients were followed up for 12 to 18 months with an average of (16.91±1.22) months. The in-hospital mortality rate in the intervention group was 2.82% (2/71), and that in the control group was 16.30% (15/92), the difference between two groups was statistically significant(χ2=6.455, P<0.05). After the intervention, SaO2, PaO2 and OI in two groups were higher than those before the intervention(P<0.05), and after the intervention, SaO2, PaO2 and OI in two groups were statistically significant(P<0.05). Hb and PLT in two groups after intervention were higher than those before intervention (P<0.001), and there was statistically significant difference in Hb and PLT between two groups after intervention (P<0.05). The Harris score of hip joint, HSS score of knee joint and AOFAS score of ankle joint in both groups after 3 months of treatment were better than those before treatment (P<0.05). The total clinical effective rate of the intervention group was higher than that of the control group(χ2=4.194, P<0.05). The total incidence of complications in the intervention group was lower than that in the control group(χ2=4.747, P<0.05).@*CONCLUSION@#DCO strategy is helpful to reduce the in-hospital mortality of patients with FES associated with long shaft fracture of lower extremities, eliminate FES symptoms and stabilize vital signs, gain time advantage for phase Ⅱ definitive surgery, and has significant clinical intervention effect, which is worth popularizing.

Analysis of the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma (ACC), and to analyze the prognostic factors. Methods: Data of 82 patients (43 females and 39 males, at a median age of 49 years old) with sinonasal and skull base ACC who were admitted to XuanWu Hospital, Capital Medical University between June 2007 and June 2021 were analyzed retrospectively. The patients were staged according to American Joint Committee on Cancer (AJCC) 8th edition. The disease overall survival(OS) and disease-free survival(DFS) rates were calculated by Kaplan-Meier analysis. Cox regression model was used for multivariate prognostic analysis. Results: There were 4 patients with stage Ⅱ, 14 patients with stage Ⅲ, and 64 patients with stage Ⅳ. The treatment strategies included purely endoscopic surgery (n=42), endoscopic surgery plus radiotherapy (n=32) and endoscopic surgery plus radiochemotherapy (n=8). Followed up for 8 to 177 months, the 5-year OS and DFS rates was 63.0% and 51.6%, respectively. The 10-year OS and DFS rates was 51.2% and 31.8%, respectively. The multivariate Cox regression analysis showed that late T stage and internal carotid artery (ICA) involvement were the independent prognostic factors for survival in sinonasal and skull base ACC (all P<0.05). The OS of patients who received surgery or surgery plus radiotherapy was significantly higher than that of patients who received surgery plus radiochemotherapy (all P<0.05). Conclusions: Endoscopic transonasal surgery or combing with radiotherapy is an effective procedure for the treatment of sinonasal and skull base ACC. Late T stage and ICA involvement indicate poor prognosis.