Relationship between histone deacetylase gene polymorphism and type 2 diabetes mellitus in Bai and Han populations in Dali of Yunnan Province / 中国基层医药

Objective:To investigate the relationship between histone deacetylase (HDAC) gene polymorphism and type 2 diabetes mellitus (T2DM) in Bai and Han populations in Dali of Yunnan province.Methods:A total of 148 patients with T2DM of Bai and Han nationalities who received treatment in Dali Bai Autonomous Prefecture People's Hospital from May 2019 to March 2021 were included in the T2DM group. An additional 100 healthy controls of Bai and Han nationalities who concurrently received physical examination in the same hospital from May 2019 to December 2020 were included in the normal control group. The susceptibility genes of T2DM were detected using the Taqman MGB probe method. The susceptibility gene loci were amplified using polymerase chain reaction. The whole sequence of susceptibility gene was sequenced.Results:There were no significant differences in the distribution frequencies of rs2530223 genotype, rs11741808 genotype, rs2547547 genotype, and rs1741981 genotype between Bai and Han populations (all P > 0.05). There was a significant difference in blood lipid level between four loci ( t = -1.06, -0.19, 0.39, -2.12, -2.04, 0.16, 1.47, < 0.01, -0.16, -3.17, -2.93, 0.69, -2.58, -2.33, all P < 0.05). There was a significant difference in homeostasis model assessment of insulin resistance between different states (all P < 0.05). The frequency distributions of each genotype and each allele did not differ significantly between healthy control people of Bai nationality and T2DM patients of Bai nationality and between healthy control people of Han nationality and T2DM patients of Han nationality (all P > 0.05). Logistic regression analysis showed that the polymorphism was not an independent risk factor for T2DM. Conclusion:The relationships between HDAC gene polymorphism and T2DM, obesity and dyslipidemia differ between Bai and Han populations.

Application and prospect of gene therapy for fundus vascular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Value of the combined use of aminotransferase-to-platelet ratio index and total bile acid for predicting parenteral nutrition-associated cholestasis in preterm infants with gestational age <34 weeks / 中国当代儿科杂志

OBJECTIVES@#To explore the value of the combined use of aspartate aminotransferase-to-platelet ratio index (APRI) and total bile acid (TBA) for predicting parenteral nutrition-associated cholestasis (PNAC) in preterm infants with gestational age <34 weeks.@*METHODS@#A retrospective analysis was performed on medical data of 270 preterm infants born at <34 weeks of gestation who received parenteral nutrition (PN) during hospitalization in the First Affiliated Hospital of Wannan Medical College from January 2019 to September 2022, including 128 infants with PNAC and 142 infants without PNAC. The medical data between the two groups were compared, and predictive factors for the development of PNAC were explored through multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of APRI alone, TBA alone, and the combination of both for predicting PNAC.@*RESULTS@#TBA levels in the PNAC group after 1, 2, and 3 weeks of PN were higher than those in the non-PNAC group (P<0.05). APRI in the PNAC group after 2 and 3 weeks of PN was higher than that in the non-PNAC group (P<0.05). Multivariate logistic regression analysis showed that elevated APRI and TBA after 2 weeks of PN were predictive factors for PNAC in preterm infants (P<0.05). ROC curve analysis showed that the sensitivity, specificity, and area under the curve (AUC) for predicting PNAC by combining APRI and TBA after 2 weeks of PN were 0.703, 0.803, and 0.806, respectively. The AUC for predicting PNAC by combining APRI and TBA was higher than that of APRI or TBA alone (P<0.05).@*CONCLUSIONS@#After 2 weeks of PN, the value of combining APRI and TBA for predicting PNAC is high in preterm infants with gestational age <34 weeks.

Roles and perspectives of inflammatory factors in diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy is the leading cause of blindness in the working-age population, in which diabetic macular edema(DME)is the most common reason resulting in the vision impairment. Studies showed that inflammation factors play an important role in the pathogenesis and development of DME. Chronic hyperglycemia activates several biochemical pathways, leading to retinal hypoxia, oxidative stress and chronic inflammation. Intraretinal inflammation-related cells, such as microglia, monocytes/macrophages, Müller cells and retinal pigment epithelial cells, become activated and release a large number of inflammation-related factors and mediators, including the complement system, vascular endothelial growth factor(VEGF), placental growth factor(PlGF), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6 and IL-8, etc., resulting in the breakdown of the blood-retinal barrier and neuronal degeneration. In addition, up-regulatethe expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)by retinal vascular endothelial cells increased the adhesion of leukocyte and leukostasis, further aggravating retinal hypoxia and breakdown of the blood-retinal barrier, leading to the increased retinal vascular leakage and macular edema. Therefore, early treatment with anti-VEGF and anti-inflammatory are pivotal for the treatment of DME. In this review, we will discuss the role of inflammation factors in the pathogenesis of DME and the research status of the targeted drugs targeting inflammation, so as to provide reference for the treatment of DME.

A Dataset on the Status Quo of Health and Health-Related Behaviors of Chinese Youth: A Longitudinal Large-Scale Survey in the Secondary School Students of Shandong Province / 中国医学科学杂志(英文版)

This data article describes data acquired from the Database of Youth Health (DYH) program. The DYH program consisted of a multi-wave survey conducted annually in the academic year 2015/2016, 2016/2017, 2017/2018, and 2020/2021 to investigate the status quo of health and health-related behaviors of Chinese junior and senior high school students. A total of 99,327 students from 186 secondary schools in 17 cities of Shandong province participated in the survey. The dataset is longitudinal and consists of rich parameters in aspects of individual information, social-economic status, social interaction, nutrition and diet, psychological cognition, mental health, school adaptation, quality of life, spare-time physical activity, risk behaviors, and physical fitness evaluation results based on the National Student Physical Fitness and Health 2014. It is the first open shared dataset about Chinese adolescents' health and health-related behaviors. It would be valuable and beneficial for policy makers, educational institutions, and other stakeholders to generate or adjust the existing strategies for improving Chinese adolescents' wellbeing.

Effect of combination of acupuncture and psychological intervention on attention, response inhibition and cerebral blood flow in children with attention deficit hyperactivity disorder / 中国针灸

OBJECTIVE@#To observe the clinical curative effect on attention deficit hyperactivity disorder (ADHD) and explore the relevant mechanism of acupuncture in treatment.@*METHODS@#A total of 100 ADHD children were randomized into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases, 1 case dropped off). In the control group, the routine psychological intervention was used. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6), Baihui (GV 20), Sishencong (EX-HN 1), etc., once daily, for 3 months. The Cambridge neuropsychological tests automated battery (CANTAB) was adopted to evaluate attention and response inhibition in two groups before and after treatment. Digi-Lite color transcranial Doppler was used to measure cerebral arterial blood velocity. The therapeutic effect was compared between the two groups.@*RESULTS@#Regarding evaluation of attention, the mean delay time in the observation group after treatment was shorter than that before treatment and that in the control group separately (@*CONCLUSION@#Acupuncture combined with psychological intervention may improve attention and response inhibition in ADHD children, which is possibly related to the regulation of cerebral blood flow.

Regulatory Effect of Modified Liu Junzitang on Immune Function, Nutritional Status and Intestinal Microecology in Advanced Gastric Cancer Patients with Syndrome of Deficiency of Qi and Blood / 中国实验方剂学杂志

Objective:To explore the regulatory effect of modified Liu Junzitang on the immune function， nutritional status and intestinal microecology in advanced gastric cancer patients with syndrome of deficiency of Qi and blood. Method:The 86 advanced gastric cancer patients with syndrome of deficiency of Qi and blood were randomly divided into control group and observation group according to their admission numbers， with 43 cases in each group. The control group was given Yiqi Yangxue oral liquid on the basis of basic treatment while the observation group was given modified Liu Junzitang. After 4 weeks， compare the clinical efficacy of two groups of patients， traditional Chinese medicine （TCM） syndrome score， gastrointestinal function recovery， adverse reaction and quality of life， immune function， T cell subsets CD3⁺， CD4⁺， CD8⁺， C₃ and C₄ levels， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， nutritional status： albumin （propagated）， prealbumin （PA）， serum total protein （TP） and hemoglobin （Hb） content changes， the intestinal micro ecology： <italic>Bifidobacterium</italic>， <italic>Lactobacillus</italic>， <italic>Enterococcus aureus</italic>， <italic>Escherichia coli</italic> content changes. Result:The total effective rate of the observation group was 95.35% （41/43）， which was significantly higher than 79.07% （34/43） of the control group （<italic>χ²</italic>=5.108，<italic>P</italic><0.05）， after treatment， the TCM syndromes such as dizziness， pale complexion， palpitation， shortness of breath and fatigue in the observation group were significantly lower than those in the control group （<italic>P</italic><0.05）， the bowel sound recovery， exhaust and defecation time of the observation group were significantly lower than those of the control group （<italic>P</italic><0.05）， the quality of life scores in the observation group， such as the nature-to-human correspondence， form and spirit integration， specific modules， functional areas， and overall health score， were significantly higher than those in control group （<italic>P</italic><0.05）， the CD3⁺， CD4⁺， CD4⁺/CD8⁺， C₃， C₄， IgA， immune function indexes such as IgG and IgM were significantly higher than those of the control group， and the CD8⁺ level was lower than which of control group （<italic>P</italic><0.05）， the nutritional status levels such as Alb， PA， TP and Hb in the observation group were significantly higher than those of the control group （<italic>P</italic><0.05）， <italic>Bifidobacterium</italic>， <italic>Lactobacillus</italic>， and <italic>E. faecalis </italic>in the observation group were higher than those in the control group， and <italic>E. coli</italic> was lower than the control group （<italic>P</italic><0.05）， the adverse reaction rate of the observation group was 11.63% （5/43） and the control group was 16.28% （7/43） ， and there was no statistical difference between two groups. Conclusion:Modified Liu Junzitang has a good clinical effect on advanced gastric cancer patients with syndrome of deficiency of Qi and blood. It can improve TCM syndromes and gastrointestinal function， improve quality of life， and its mechanism is related to improving immune function， enhancing nutritional status， and improving intestinal microecology， and it has good safety.

The role of adenine nucleotide and its metabolites in regulating the homeostasis of glucose and lipid metabolism / 生理学报

Glucose and lipid metabolism is the most fundamental metabolic activity of higher organisms. This process is affected by both genetic polymorphisms and environmental factors. Excessive uptake and accumulation of lipids lead to obesity and disorder of glucose metabolic homeostasis characterized by insulin resistance and hyperglycemia, suggesting that the cross-regulation between lipid and glucose metabolism happens precisely at organ, cellular and molecular levels by known mechanisms. Adenine nucleotides and their metabolites have emerged as mediators in the mutual regulation of glucose and lipid metabolism. This review summarizes the roles of purinergic signaling induced by fatty acids in glucose metabolism and the development of type 2 diabetes.

Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis / 中华医学杂志(英文版)

BACKGROUND@#Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.@*METHODS@#This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12.@*RESULTS@#A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.@*CONCLUSION@#Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.

Effect of maternal immune level at different pregnancy stages on cow's milk protein allergy in infants / 中国当代儿科杂志

OBJECTIVE@#To study the association between maternal Th1/Th2 immune level at different pregnancy stages and cow's milk protein allergy (CMPA) in infants.@*METHODS@#The healthy women with a singleton pregnancy, as well as their offspring, who attended Yidu Central Hospital of Weifang and Qingzhou Traditional Chinese Medicine Hospital from July 2016 to December 2018 were enrolled. The maternal levels of interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) at the second and third trimesters of pregnancy were measured. A CMPA questionnaire survey was conducted within one year after birth. Food avoidance and cow's milk oral challenge tests were performed in infants suspected of CMPA. The 48 infants who met the diagnostic criteria for CMPA were included in the observation group, and the remaining 977 normal infants were included in the control group. A univariate analysis was performed on the infants with CMPA. A Poisson regression analysis was used to determine the association between maternal Th1/Th2 immune factors at different pregnancy stages and CMPA.@*RESULTS@#The detection rate of CMPA was 4.68%. The clinical manifestations included the symptoms of the digestive system, skin, and respiratory system and other symptoms. The univariate analysis showed that compared with the control group, the observation group had significantly higher incidence rates of maternal food allergy and maternal history of allergic diseases (P<0.05) and a significantly lower breastfeeding rate (P<0.05). The observation group had significantly lower maternal levels of IL-2 (second and third trimesters) and IFN-γ (third trimester) than the control group (P<0.05). Maternal low IFN-γ at the third trimester and maternal low IL-2 at the second and third trimesters were significantly associated with CMPA in infants (P<0.05). After correction of the factors of breastfeeding, maternal food allergy, and maternal history of allergic diseases, it was found that maternal low IL-2 and IFN-γ at the third trimester were still significantly associated with CMPA in infants (P<0.05).@*CONCLUSIONS@#The maternal decrease in Th1 level at the third trimester of pregnancy may lead to the change in fetal immunity and thus increase the risk of CMPA in offspring.

Asymptomatic SARS-CoV-2 infection in children: a clinical analysis of 20 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical and epidemiological features of children with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.@*METHODS@#The clinical data of 20 children who were diagnosed with asymptomatic SARS-CoV-2 infection from January 20 to March 4, 2020 were analyzed.@*RESULTS@#Among the 20 children, there were 7 boys (35%) and 13 girls (65%), aged 8 months to 14 years (mean 8±5 years). All these children had no clinical manifestations and attended the hospital for an epidemiological history of SARS-CoV-2. Nineteen children were shown with family aggregation of SARS-CoV-2 infection. Nasopharyngeal swabs were PCR-positive for SARS-CoV-2 in all 20 children. There were 4 children (20%) of mild type, 16 children (80%) of common type, and no children of severe type or critical type. The mean peripheral blood leukocyte count was (6.8±3.5)×10/L, and 7 children had an abnormal peripheral blood leukocyte count, with an increase in 5 children and a reduction in 2 children. One child had a decreased absolute value of lymphocytes (0.87×10/L), 3 children had an increased erythrocyte sedimentation rate (20-42 mm/h), 7 children had an increased lactate dehydrogenase level (>400 U/L), and 4 children had an increased blood lactate level (>1.6 mmol/L). Chest CT showed single or multiple small nodule shadows, patchy shadows, and ground-glass shadows in the middle or lateral lobe of lungs or under the pleura in 13 children.@*CONCLUSIONS@#Pediatric cases of asymptomatic SARS-CoV-2 infection mostly occur with family aggregation. Most of the children with asymptomatic infection have no obvious abnormalities in blood routine and other laboratory tests. Changes in chest CT scan can be used as an aid for early diagnosis of asymptomatic infection in children.

Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer: A Case Report / 中国医学科学杂志(英文版)

Skin reaction or dermatological toxicities induced by immunotherapy is common. It usually manifests skin rash or erythema and can be cured by skin lotion or steroid. Nivolumab, a human IgG4 programmed cell death protein 1 (PD-1) inhibitor, blocks T cells activation preventing signal and allows the immune system to clear cancer cells. Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA, with less than 10% unusual skin reaction, like sensory neuropathy, peeling skin, erythema multiforme, vitiligo, and psoriasis. Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity. The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies, but the risk of side effects may be high. We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy. The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events. Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

Effect of primary neck-shaft angle after operation on the treatment of proximal humerus fracture by locking plate / 中国骨伤

<p><b>OBJECTIVE</b>To explore the effect of postoperative initial neck stem angle on the treatment of proximal humeral fractures with locking plate.</p><p><b>METHODS</b>From June 2014 to Septembetr 2016, 62 patients with proximal humeral fractures underwent internal fixation with locking plates were retrospectively analyzed, including 29 males and 33 females with an average age of(55.95±9.48) years old ranging from 34 to 74 years old. According to the difference of the initial neck stem angle, the patients were divided into three groups, 15 patients in the varus group had less than 127° postoperative initial neck-shaft angle, 36 patients in the normal group had 127° to 145° postoperative initial neck-shaft angle, 11 patients in the valgus group had more than 145° postoperative initial neck-shaft angle. The operating time, fracture healing time, complications, the visual analogue scale(VAS) and shoulder functional Neer scores among three groups were compared for analysis.</p><p><b>RESULTS</b>All 62 patients were followed up for 17.2 months(ranged 12 to 38 months). Operative time, fracture healing time and VAS were(2.37±0.59) hours, (3.99±0.48) months and(3.67±2.02) points in the varus group;(2.60±0.49) hours, (3.78±0.49) months and(3.22±2.06) points in the normal group;(2.75±0.39) hours, (3.82±0.42) months and (4.09±1.58) points in the valgus group. There was no statistical difference in operating time, fracture healing time and VAS among these groups(>0.05). The Neer score(87.14±6.48) in the normal group and(84.31±9.05) in the valgus group was significantly better than(75.93±9.77) in the varus group (<0.05). Among them, 4 cases occurred complications in the varus group;2 cases in the normal group;while no complication occurred in the valgus group.</p><p><b>CONCLUSIONS</b>The internal fixation with locking plates of the proximal humerus fractures with postoperative initial neck-shaft angle more than 127° can reduce complications, improve shoulder function and allow for better postoperative outcome.</p>

Value of combined determination of neutrophil CD64 and procalcitonin in early diagnosis of neonatal bacterial infection / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the value of combined determination of neutrophil CD64 and procalcitonin (PCT) in the early diagnosis of neonatal bacterial infection.</p><p><b>METHODS</b>According to discharge diagnosis, 37 neonates with bacterial infection were divided into sepsis (n=15) and ordinary infection (non-sepsis) groups (n=22). Twenty-one neonates without infection who were hospitalized during the same period of time were enrolled as the control group. Venous blood samples were collected immediately after admission. Flow cytometry was used to measure the serum level of neutrophil CD64. Chemiluminescence and immune transmission turbidimetry were used to measure the serum levels of PCT and CRP respectively.</p><p><b>RESULTS</b>The sepsis group had higher serum levels of neutrophil CD64, PCT, and CRP than the control group (P<0.01), the ordinary infection group had a higher serum level of neutrophil CD64 than the control group (P<0.01), and the sepsis group had higher serum levels of PCT and CRP than the ordinary infection group (P<0.01). The areas under the ROC curve (AUC) of neutrophil CD64, PCT, and CRP in diagnosing bacterial infection were 0.818, 0.818, and 0.704 respectively, and the AUC of combined neutrophil CD64 and PCT was 0.926. A combination of neutrophil CD64 and PCT had a sensitivity of 97.29% and an accuracy of 89.65% in the early diagnosis of neonatal bacterial infection.The sensitivity and accuracy were higher than those of a combination of CRP and neutrophil CD64 or PCT as well as neutrophil CD64, PCT, or CRP alone for the early diagnosis of neonatal bacterial infection.</p><p><b>CONCLUSIONS</b>The combined determination of neutrophil CD64 and PCT can improve the sensitivity and accuracy in the diagnosis of neonatal bacterial infection, which helps with early identification of bacterial infection.</p>

Study of axonal guidance growth cue netrin-1 on nano-materials in nerve regeneration / 中国药理学与毒理学杂志

Nerve regeneration is a major problem in our society after nerve injury.With the development of nanotechnology,some nano-materials,such as carbon nanotubes and graphene with electrical conductivity,have been used to promote neuronfunctional recovery.Some of the nano-materials,however,are neurotoxic and cause neuronal apoptosis.Nerve injury often leads to the disruption of axons,and broken axons cannot form synapse with target neurons,which affects the repair and regeneration of nerves.Netrin-1 is an important cue in neurogenesis,which can guide the growth and migration of axons and synapse formation during neuronal regeneration.However,some growth factors are used to decorate the surface of nanomateriaes to decrease the toxicity in medicine,but the molecular mechanism by which netrin-1 mediates the toxicity of nanomaterials is not clear yet.In this study,we investigated the nano-materials and the function of netrin-1 in neuronal regeneration in recent years.We have proved that netrin-1 can not only guide the growth and migration of axon and synapse formation,but also promote functional recovery of the neurons which are injured by the toxicity of nanomaterials.Our review will provide a theoretical basis for neuronal regeneration by nanomaterials.

Neuroprotective effect of Nogo-66 receptor silencing in preterm rats with brain injury caused by intrauterine infection / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of Nogo-66 receptor (NgR) silencing with specific small interfering RNA (siRNA) on brain injury repair in preterm rats with brain injury caused by intrauterine infection and related mechanism of action.</p><p><b>METHODS</b>The pregnant Sprague-Dawley rats (with a gestational age of 15 days) were selected, and premature delivery was induced by RU486 or lipopolysaccharide (LPS). The preterm rats delivered by those treated with RU486 were selected as the control group. The preterm rats with brain injury caused by intrauterine infection induced by LPS were divided into model, empty vector, and NgR-siRNA groups, with 36 rats in each group. The rats in the control and model groups were given routine feeding only, and those in the empty vector and NgR-siRNA groups were given an injection of lentiviral empty vector or NgR-siRNA lentivirus via the lateral ventricle on postnatal day 1 (P1) and then fed routinely. On P3, P7, and P14, 8 rats in each group were randomly selected and sacrificed to harvest the brain tissue. RT-PCR was used to measure the mRNA expression of NgR. Western blot was used to to measure the protein expression of active RhoA. The immunofluorescence histochemistry was used to determine the degree of activation of microglial cells and the morphology of oligodendrocyte precursor cells (OPCs). Hematoxylin and eosin staining was used to observe the pathological changes in brain tissue. The behavioral score was evaluated on P30.</p><p><b>RESULTS</b>On P3, the NgR-siRNA group had significantly lower mRNA expression of NgR and protein expression of active RhoA in brain tissue than the model and empty vector groups (P<0.05). In each group, the mRNA expression of NgR was positively correlated with the protein expression of active RhoA (P<0.05). The results of immunofluorescence histochemistry showed that on P3, the NgR-siRNA group had a significantly reduced fluorescence intensity of the microglial cells labeled with CD11b compared with the model and empty vector groups (P<0.05). The OPCs labeled with O4 antibody in the four groups were mainly presented with tripolar cell morphology. The results of pathological examination showed a normal structure of white matter with clear staining in the periventriclar area in the control group, a loose structure of white matter with disorganized fibers and softening lesions in the model and empty vector groups, and a loose structure of white matter with slightly disorganized fibers, slight gliocyte proliferation, and no significant necrotic lesions in the NgR-siRNA group. As for the behavioral score, compared with the model and empty vector groups, the NgR-siRNA group had a higher score in the suspension test, a longer total activity distance, and greater mean velocity and number of squares crossed, as well as a shorter time of slope test and a shorter time and distance of activity in the central area (P<0.05), while there were no significant differences in these parameters between the NgR-siRNA and control groups (P>0.05).</p><p><b>CONCLUSIONS</b>NgR silencing with specific siRNA can effectively silence the expression of NgR in pertem rats with brain injury caused by interauterine infection and has a significant neuroprotective effect in brain injury repair.</p>

A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules

Single particle analysis, which can be regarded as an average of signals from thousands or even millions of particle projections, is an efficient method to study the three-dimensional structures of biological macromolecules. An intrinsic assumption in single particle analysis is that all the analyzed particles must have identical composition and conformation. Thus specimen heterogeneity in either composition or conformation has raised great challenges for high-resolution analysis. For particles with multiple conformations, inaccurate alignments and orientation parameters will yield an averaged map with diminished resolution and smeared density. Besides extensive classification approaches, here based on the assumption that the macromolecular complex is made up of multiple rigid modules whose relative orientations and positions are in slight fluctuation around equilibriums, we propose a new method called as local optimization refinement to address this conformational heterogeneity for an improved resolution. The key idea is to optimize the orientation and shift parameters of each rigid module and then reconstruct their three-dimensional structures individually. Using simulated data of 80S/70S ribosomes with relative fluctuations between the large (60S/50S) and the small (40S/30S) subunits, we tested this algorithm and found that the resolutions of both subunits are significantly improved. Our method provides a proof-of-principle solution for high-resolution single particle analysis of macromolecular complexes with dynamic conformations.

The Dose-response of Intrathecal Ropivacaine Co-administered with Sufentanil for Cesarean Delivery under Combined Spinal-epidural Anesthesia in Patients with Scarred Uterus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spinal anesthesia is considered as a reasonable anesthetic option in lower abdominal and lower limb surgery. This study was to determine the dose-response of intrathecal ropivacaine in patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia.</p><p><b>METHODS</b>Seventy-five patients with scarred uterus undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this randomized, double-blinded, dose-ranging study. Patients received 6, 8, 10, 12, or 14 mg intrathecal hyperbaric ropivacaine with 5 μg sufentanil. Successful spinal anesthesia was defined as a T4sensory level achieved with no need for epidural supplementation. The 50% effective dose (ED50) and 95% effective dose (ED95) were calculated with a logistic regression model.</p><p><b>RESULTS</b>ED50and ED95of intrathecal hyperbaric ropivacaine for patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia (CSEA) were 8.28 mg (95% confidence interval [CI]: 2.28-9.83 mg) and 12.24 mg (95% CI: 10.53-21.88 mg), respectively.</p><p><b>CONCLUSION</b>When a CSEA technique is to use in patients with scarred uterus for an elective cesarean delivery, the ED50and ED95of intrathecal hyperbaric ropivacaine along with 5 μg sufentanil were 8.28 mg and 12.24 mg, respectively. In addition, this local anesthetic is unsuitable for emergent cesarean delivery, but it has advantages for ambulatory patients.</p>

ED 50 and ED 95 of intrathecal bupivacaine coadministered with sufentanil for cesarean delivery under combined spinal-epidural in severely preeclamptic patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated, and there is no indwelling epidural catheter or contraindication to spinal anesthesia. However, the ideal dose of intrathecal bupivacaine has not been quantified for cesarean delivery for severe preeclamptic patients. This study aimed to determine the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery.</p><p><b>METHODS</b>Two hundred severely preeclamptic patients are undergoing elective cesarean delivery under combined spinal-epidural anesthesia enrolled in this randomized, double-blinded, dose-ranging study. Patients received 4 mg, 6 mg, 8 mg, or 10 mg intrathecal hyperbaric bupivacaine with 2.5 μg sufentanil. Successful spinal anesthesia was defined as a T6 sensory level achieved within 10 minutes after intrathecal drug administration and/or no epidural supplement was required during the cesarean section. The ED 50 and ED 95 were calculated with a logistic regression model.</p><p><b>RESULTS</b>ED 50 and ED 95 of intrathecal bupivacaine for successful spinal anesthesia were 5.67 mg (95% confidence interval [CI]: 5.20-6.10 mg) and 8.82 mg (95% CI: 8.14-9.87 mg) respectively. The incidence of hypotension in Group 8 mg and Group 10 mg was higher than that in Group 4 mg and Group 6 mg (P < 0.05). The sensory block was significantly different among groups 10 minutes after intrathecal injection (P < 0.05). The use of lidocaine in Group 4 mg was higher than that in other groups (P < 0.05). The use of phenylephrine in Group 8 mg and Group 10 mg was higher than that in the other two groups (P < 0.05). The lowest systolic blood pressure before the infant delivery of Group 8 mg and Group 10 mg was lower than the other two groups (P < 0.05). The satisfaction of muscle relaxation in Group 4 mg was lower than other groups (P < 0.05). There was no significant difference in patients' satisfaction and the newborns' Apgar score and the blood gas analysis of umbilical artery serum (P > 0.05).</p><p><b>CONCLUSION</b>Our study showed that the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery were 5.67 mg and 8.82 mg, respectively. In addition, decreasing the dose of intrathecal bupivacaine could reduce the incidence of maternal hypotension.</p>

Bayesian localization microscopy based on intensity distribution of fluorophores

Super-resolution microscopy techniques have overcome the limit of optical diffraction. Recently, the Bayesian analysis of Bleaching and Blinking data (3B) method has emerged as an important tool to obtain super-resolution fluorescence images. 3B uses the change in information caused by adding or removing fluorophores in the cell to fit the data. When adding a new fluorophore, 3B selects a random initial position, optimizes this position and then determines its reliability. However, the fluorophores are not evenly distributed in the entire image region, and the fluorescence intensity at a given position positively correlates with the probability of observing a fluorophore at this position. In this paper, we present a Bayesian analysis of Bleaching and Blinking microscopy method based on fluorescence intensity distribution (FID3B). We utilize the intensity distribution to select more reliable positions as the initial positions of fluorophores. This approach can improve the reconstruction results and significantly reduce the computational time. We validate the performance of our method using both simulated data and experimental data from cellular structures. The results confirm the effectiveness of our method.