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Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.
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Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.
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Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.
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Objective To compare the influence between self-monitoring of blood gluocose(SMBG)combined with digital diabetes management and traditional management mode on the related clinical indexes in the patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM treated in the endocrinology and metabolism outpatient department of this hospital from January 2022 to June 2022 and meeting the inclusion criteria of this study were successively included.They were divided into the experimental group and control group.The experimental group was managed by SMBG combined with digital diabetes man-agement mode,while the control group adopted the traditional management mode,the outpatient clinic follow up once a month.After 6 months of follow-up,fasting blood glucose,glycosylated hemoglobin(HbA1c),low density lipoprotein cholesterol(LDL-C)and urinary microalbumin/creatinine ratio(UACR)were compared between the two groups.Results The FBG,HbA1c,LDL-C,and UACR of the experimental group decreased after intervention when compared with baseline.Compared with the control group,the FBG[8.7(7.7,9.2)mmol/L vs.10.8(8.8,12.7)mmol/L,Z=-4.660,P＜0.001],HbA1c[6.3％(5.3,7.8)％vs.8.5％(7.2,10.0)％,Z=-5.130,P＜0.001],LDL-C[2.6(1.8,3.1)mmol/L vs.3.3(2.6,4.0)mmol/L,Z=-4.112,P＜0.001],UACR[16.1(3.5,46.5)mg/g vs.58.4(11.9,108.0)mg/g,Z=-2.220,P=0.026]for patients in the expriemental group after intervention were significantly decreased.Conclusion SMBG combined with digital diabetes management model can significantly improve the clinical indicators of patients.
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Objective To observe the clinical efficacy of Qigui Tongluo Oral Liquid(a hospital preparation developed by Guangdong Second Traditional Chinese Medicine Hospital and being composed of Astragali Radix,Angelicae Sinensis Radix,Notoginseng Radix et Rhizoma,Paeoniae Radix Rubra,Achyranthis Bidentatae Radix,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Pheretima,etc.)combined with moxibustion for the treatment of chronic fatigue syndrome(CFS)of qi deficiency and blood stasis type on the basis of qi-collateral theory.Methods A retrospective study was conducted in 60 CFS patients with qi deficiency and blood stasis type.The patients were divided into an observation group and a control group,with 30 patients in each group according to the therapy.The control group was treated with mild moxibustion on Shenque(CV8)point with moxa sticks,and the observation group was treated with Qigui Tongluo Oral Liquid on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,Fatigue Scale-14(FS-14)scores,serum immunoglobulin IgA,IgM,IgG levels,and cortisol(COR)level in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 96.67%(29/30),and that of the control group was 80.00%(24/30).The intergroup comparison showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores and FS-14 scores of patients in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the effect on decreasing TCM syndrome scores and FS-14 scores in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum IgA and IgG levels of the two groups as well as the serum IgM and COR levels of the observation group were significantly increased compared with those before treatment(P＜0.01),and the effect of the observation group on increasing serum IgA,IgM,IgG,and COR levels was significantly superior to that of the control group(P＜0.05 or P＜0.01).(4)During the treatment,there were no significant adverse reactions occurring in the two groups.Conclusion Healthy-qi deficiency and collateral obstruction contribute to the core pathogenesis of CFS.Based on the TCM qi-collateral theory and following the therapeutic principle of replenishing deficiency and unblocking collaterals,Qigui Tongluo Oral Liquid combined with moxibustion for the treatment of CFS patients with qi deficiency and blood stasis type can achieve certain efficacy.The combined therapy could significantly alleviate the clinical symptoms,improve the immunity level,and regulate the neuro-endocrine-immune(NEI)network of the patients.
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Objective To investigate the effect of transmembrane protein CD147 expression on AIM2 inflammasome-mediated pyroptosis and proliferation of cervical cancer cells.Methods Western Blot was used to detect the expression of CD147 in cervical cancer cell lines SiHa(HPV+)and C33a(HPV-)and normal cervical epithelial cells H8(HPV+)and HCer Epic(HPV-).SiHa cells were transfected with lentivirus to down-regulate the expression of CD147.According to the different treatments,SiHa cells were divided into SiHa group,negative control group(shCD147-NON),knockdown group 1(shCD147-1)and knockdown group 2(shCD147-2).The transfection effect was verified by Western Blot,RT-qPCR and green fluorescence expression.The protein and mRNA expressions of AIM2,Caspase-1,IL-18 and GSDMD were detected by Western Blot and RT-qPCR.The lactate dehydrogenase(LDH)release was measured in the cell culture supernatant,and the cell morphology was observed under the fluorescence inverted microscope;the proliferation ability of cells was measured by CCK-8 and the colony formation ability was measured by cell cloning experiments.Results Western Blot results showed that CD147 protein expression in SiHa cells was the highest compared with that in HCerEpic cells.CD147 low expression lentivirus effectively down-regulated the expression of CD147 in SiHa cells.The results of Western Blot and RT-qPCR experiments showed that the expression of AIM 2,Caspase-1,IL-18,GSDMD protein and mRNA increased in shCD147-1 and shCD147-2 group(P<0.05).Lactate dehydrogenase(LDH)release assay showed that compared with the SiHa group,the shCD147 group had a significant increase in LDH release(P<0.05).Fluorescence inverted microscope showed that the shCD147 group had swelling and vacuolization,showing typical pyroptosis.Compared with the SiHa group,the shCD147-1 and shCD147-2 groups had significantly reduced the cell proliferation and colony formation ability(P<0.05).Conclusion Low expression of CD147 effectively up-regulates the expression of AIM2 inflammation-related factors in cervical cancer SiHa cells,induces the pyroptosis,and inhibits the cell proliferation and cloning.
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Objective:To study the distribution and changes of dopamine transporter (DAT) in guinea pig eyes under different light patterns.Methods:Thirty-six 3-week-old white ordinary-grade guinea pigs were randomly selected and divided into groups of 10 000 lx, 5 000 lx, and 500 lx, with 12 guinea pigs in each group exposed to strong light, medium strong light, and normal light, respectively.Each group was randomly divided into 3 subgroups, with 4 guinea pigs in each subgroup.The 3 subgroups of 500 lx group received light exposure for 5, 20, and 40 minutes, respectively.The 3 subgroups of 5 000 lx group received light exposure for 2, 4, and 40 minutes, respectively.The 3 subgroups of 10 000 lx group received light exposure for 2, 5, and 20 minutes, respectively.After light treatment, each group of guinea pigs was injected with 99mTc-TRODAT-1 for SPECT DAT imaging, and image data were collected by Micro-SPECT.The region of interest (ROI) of guinea pig retinas was analyzed using Micro-CT software.The counts of ROI were expressed as Sum, which reflected the relative distribution or density of DAT.The DAT density between experimental and control eyes of guinea pigs after light exposure, the differences in DAT density between guinea pig eyes under different light intensities, the differences in DAT density between guinea pig eyes after different light durations, and the cumulative and interactive effects of light intensity and light duration on DAT aggregation in guinea pigs were compared.Another 3 guinea pigs were selected, and after light exposure, the 3 guinea pigs' eyes underwent continuous image acquisition for 6 hours at 20-minute intervals, and 18 images per guinea pig were acquired to analyze the trend of DAT density in guinea pig eyes over time.This study was approved by the Ethics Committee of Shanghai General Hospital (No.2020SQ196). Results:The DAT density (Sum value) of experimental eyes at 500, 5 000, and 10 000 lx were 5 598.97±3 159.38, 8 636.78±2 503.16, and 7 407.39±2 053.41, respectively, significantly higher than 4 388.89±2 902.90, 5 981.92±3 057.44, and 5 091.32±2 039.36 of control eyes ( t=5.31, 4.69, 11.80; all at P<0.001). At 500 lx, there was a statistically significant difference in DAT density between the experimental and control eyes of guinea pigs at different light exposure durations ( F=14.01, P<0.01), while no significant difference was found at other light intensities at different light exposure durations (both at P>0.05). When the light exposure time was 5 minutes, the difference in DAT density between the experimental and control eyes of guinea pigs was significantly greater in the 10 000 lx group than in the 500 lx group ( t=-13.22, P<0.001). There was no statistically significant difference between different groups at other light exposure durations (all at P>0.05). No cumulative or interactive effects of light intensity and light duration were found on the differences in DAT density (all at P>0.05). Continuous scanning after illumination showed that DAT density in guinea pig retinas first increased to a peak over time and then gradually returned to normal values. Conclusions:Light, even under moderate or normal light levels, can cause an increase in the secretion of DAT in the retina and stimulate the production of DAT.Light intensity and duration have no cumulative or interactive effects on the distribution and density of retinal DAT.
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Objective To study the mechanical properties of titanium mesh and three-dimensional(3D)-printed metal vertebral body substitutes(VBS)to provide guidance for the selection and structural optimization of artificial vertebral implants in clinical practice.Methods The equivalent elastic modulus,equivalent yield strength,and structural failure mode of titanium mesh and 3D-printed porous,truss,and topologically optimized VBS were systematically investigated using compression tests.Results The elastic modulus of the titanium mesh(2 908.73±287.39 MPa)was only lower than that of the topologically optimized VBS.However,their structural strengths and stabilities were inadequate.The yield strength of the titanium mesh(46.61±4.85 MPa)was only higher than that of the porous VBS and it was the first to yield during compression.The porous VBS was insufficient for use as the vertebral implant owing to its poor mechanical strength(18.14±0.17 MPa-25.79±0.40 MPa).The truss VBS had good elastic modulus(2 477.86±55.19 MPa-2 620.08±194.36 MPa)and strength(77.61±0.50 MPa-88.42±1.07 MPa).However,the structural stability of the truss VBS was insufficient,and instability occurred easily during compression.The topologically optimized VBS had the highest elastic modulus(3 746.28±183.80 MPa)and yield strength(177.43±3.82 MPa)among all the tested VBS types,which could provide improved security and stability for artificial vertebral implant in vivo services.Conclusions Topology optimization results in a high strength and high stability VBS design.Moreover,it provides a large design space and great safety margin to provide increased possibilities for lightweight and new material design of future artificial vertebral implants.
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Organoids,recognized as invaluable models in tumor and stem cell research,assume a pivotal role in the meticulous analysis of diverse datasets pertaining to their growth dynamics,drug screening processes and related phenomena.However,the manual scrutiny and conventional statistical methodologies employed in handling organoid data often grapple with challenges such as diminished precision and efficiency,heightened complexity,escalated human resource requirements,and a degree of subjectivity.Acknowledging the remarkable efficacy of artificial intelligence(AI)in the realms of biology and medicine,the incorporation of AI into organoid research stands poised to enhance the objectivity,precision and expediency of analyses.This integration empowers organoids to more effectively fulfill objectives such as disease modeling,drug screening and precision medicine.Notably,significant strides have been made in AI-driven analyses of organoid image data.The amalgamation of deep learning into image analysis facilitates a more meticulous delineation of the microstructural intricacies and nuanced changes within organoids,achieving a level of accuracy akin to that of experts.This not only elevates the precision of organoid morphology and growth recognition,but also contributes to substantial time and cost savings in research endeavors.Furthermore,the infusion of AI technology has yielded breakthroughs in the processing of organoid omics data,resulting in heightened efficiency in data processing and the identification of latent gene expression patterns.This furnishes novel tools for comprehending cellular development and unraveling the intricate mechanisms underlying various diseases.In addition to image data,AI techniques applied to diverse organoid datasets,encompassing electrical signals and spectra,have realized an unbiased classification of organoid types and states,embarking on a comprehensive journey towards characterizing organoids holistically.In the pivotal domain of drug screening for organoids,AI emerges as a stalwart companion,providing robust support for real-time process monitoring and result prediction.Leveraging high-content microscopy images and sophisticated deep learning models,researchers can dynamically monitor organoid responses to drugs,effecting non-invasive detection of drug impacts and amplifying the precision and efficiency of drug screening processes.Despite the significant strides made by AI in organoid research,challenges persist,encompassing hurdles in data acquisition,constraints in sample quality and quantity,and quandaries associated with model interpretability.Overcoming these challenges necessitates dedicated future research efforts aimed at enhancing data consistency,fortifying model interpretability,and exploring methodologies for the seamless fusion of multimodal data.Such endeavors are poised to usher in a more comprehensive and dependable application of AI in organoid research.In summation,the integration of AI technology introduces unparalleled opportunities to organoid research,resulting in noteworthy advancements.Nevertheless,interdisciplinary research and collaborative efforts remain imperative to navigate challenges and propel the more profound integration of AI into organoid research.The future holds promise for AI to assume an even more prominent role in advancing organoid research toward clinical translation and precision medicine.
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Objective To explore the efficacy of unilateral biportal endoscopy(UBE)for lumbar intervertebral foramen stenosis combined with lumbar disc herniation through Sublamina approach.Methods From October 2021 to June 2022,7 elderly patients with typical symptoms of lumbar disc herniation in the intervertebral foramen area accompanied by spinal stenosis were retrospectively analyzed.There were 6 patients with lumbar disc herniation and nerve root canal stenosis at L4/5 and 1 patient at L5/S1.The mean course of disease was(8.6±2.5)months.All the patients were treated by UBE through Sublamina approach.Results Postoperative limb radicular symptoms of 7 patients were relieved.The visual analogue scale(VAS)of limb pain was significantly decreased from preoperative(8.6±1.3)to(2.1±1.1)at 2 d after the surgery(P<0.05),the Japanese Orthopaedic Association(JOA)score was significantly increased from preoperative(10.1±2.4)to(17.3±1.8)at 2 d after the surgery(P<0.05).Conclusion UBE for lumbar intervertebral foramen stenosis combined with lumbar disc herniation through Sublamina approach has a satisfactory therapeutic effect,providing a new idea for the surgical treatment of this disease.
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The ethical issue of medical genetic testing is one of the highly concerned and controversial issues in the field of life sciences.With the rapid development of genomics research,the possibility of using genetic testing for disease risk assessment in clinical events has been increased,especially in precision medical genetic testing and preventive testing.By reviewing the current status and common ethical issues of the clinical application of genetic testing,and sorting out the corresponding ethical principles,this paper proposed the ethical principles of equal respect,informed consent,privacy protection,and non-harm,aiming to help medical staff to regulate diagnosis and treatment behavior,enhance their awareness of the ethical aspects of genetic testing,as well as promote the better development of genomics research.
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@#Objective To evaluate the robustness of cardiovascular meta-analysis with use of fragility index. Methods By searching PubMed, EMbase, and Web of Science databases from 2018 to 2022, relevant literature on cardiovascular meta-analysis was systematically collected and the fragility indexes were calculated; Spearman correlation analysis was used to explore the relationship between fragility index and sample size, total number of events, effect size and its confidence interval width. Results A total of 212 meta-analyses from 29 articles were included, with a median fragility index of 11 (5, 25), a median sample size of 10 301 (3 384, 48 330), and a median total number of events of 360 (129, 1 309). Most meta-analyses chose relative risk as the effect measure (179/212), and chose Mantel-Haenszel method (102/212) and random effects model (153/212). The fragility index was positively correlated with the sample size (rs=0.56, P<0.05) and the total number of events (rs=0.61, P<0.05), and negatively correlated with confidence interval width of the effect size (rs=−0.52, P<0.05). No statistically significant results were obtained in the correlation between the fragility index and effect size. Conclusion The fragility indexes of cardiovascular meta-analyses published in comprehensive journals of high impact factors and professional cardiovascular journals are generally low, and therefore lack robustness. Fragility index is suggested to be reported in medical researches, assisting in explaining the P-value.
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Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by
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OBJECTIVE:Some studies have shown that kinesio taping has positive effects in elevating muscle strength,improving joint stability and reducing pain and oedema in patients after anterior cruciate ligament reconstruction.However,existing studies have divergent results on the clinical efficacy of kinesio taping.In this study,a meta-analysis was conducted to systematically evaluate the effect of kinesio taping in postoperative rehabilitation period following anterior cruciate ligament reconstruction. METHODS:Randomized controlled trials about the effects of kinesio taping on anterior cruciate ligament reconstruction were electronically searched in PubMed,Web of Science,Embase,The Cochrane Library,EBSCO,CNKI,WanFang,and VIP databases,from database inception to December 06,2022.The outcome measures included six continuous variables:quadriceps strength,hamstring strength,knee swelling,knee range of motion,Lysholm knee function score,and Visual Analogue Scale score.EndNote X9.1 was used to screen the literature.The Cochrane Risk Bias Assessment Tool and Jadad Scale were used to evaluate the quality of the included literature.RevMan 5.3 software was used for Meta-analysis. RESULTS:A total of 6 randomized controlled trials involving 252 patients undergoing anterior cruciate ligament reconstruction were finally included.There were 126 cases in control group and 126 in kinesio taping group.The results of Meta-analysis showed that compared with the control group,kinesio taping significantly improved hamstring strength[standardized mean difference(SMD)=0.68,95%confidence interval(CI):0.12 to 1.23,P=0.02)and reduced Visual Analogue Scale score[mean difference(MD)=-0.56,95%CI:-1.04 to-0.08,P=0.02).However,for quadriceps strength,knee swelling,knee range of motion,and Lysholm knee function score,kinesio taping did not show significant difference from the control group(P＞0.05). CONCLUSION:Kinesio taping may help to improve hamstring strength and reduce pain in patients after anterior cruciate ligament reconstruction.However,it cannot significantly improve quadriceps strength,knee swelling,knee range of motion,and functional scores.
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BACKGROUND:Bone mineral density is the clinical gold standard for determining bone strength,but bone mineral density is less sensitive to changes in bone mass,with large changes in bone mineral density only occurring when bone mass is significantly reduced,so bone mineral density has limited ability to predict changes in bone strength and fracture risk. OBJECTIVE:A model of the normal and osteoporotic hip joint was developed to analyze the stresses and deformation in the hip of normal and osteoporotic patients under single-leg standing conditions. METHODS:A healthy adult female volunteer at the age of 36 years was selected as the study subject.The CT data of the hip joint of this volunteer were obtained and saved in DICOM format.The hip joint model was reconstructed in three dimensions,and the material properties were assigned by the gray value assignment method to obtain the normal and osteoporotic hip joint models according to the empirical formula.The same boundary conditions and loads were set to simulate the stresses and deformation in the normal and osteoporotic hip joints in the single-leg standing position. RESULTS AND CONCLUSION:(1)In the finite element model of the normal and osteoporotic hip,the stress distribution was more concentrated in the medial region of the femoral neck.(2)In the hip bone,the stress distribution was mainly concentrated in the upper part of the acetabulum.(3)The stress peaks in the medial femoral neck and upper acetabulum were larger in the normal hip model than in the osteoporotic hip model,probably due to the reduced bone strength of the osteoporotic bone.(4)The peak Von Mises of both normal and osteoporotic hip models were concentrated on the medial femoral neck,and the peak Von Mises of the hip bone was smaller,indicating that the overall effect of osteoporosis on hip bone stresses was relatively small.(5)In terms of deformation in the single-leg standing position,the maximum deformation in the normal hip model was located at the acetabulum and femoral head,and the maximum deformation was located at the upper part of the greater trochanter of the femur.(6)It is suggested that the finite element analysis method to model the values of parameters related to bone tissue in osteoporosis may improve clinical prediction of bone strength changes and fracture risk.It is explained from the biomechanical view that the intertrochanteric femur and femoral neck are good sites for osteoporotic hip fractures.
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BACKGROUND:At present,postoperative timing or subjective criteria by clinicians are commonly employed to determine the return-to-sport timing for patients undergoing anterior cruciate ligament reconstruction.Unfortunately,these criteria do not adequately consider the biomechanical deficits in patients following anterior cruciate ligament reconstruction. OBJECTIVE:To explore the lower extremity kinematic and kinetic characteristics of athletes after anterior cruciate ligament reconstruction during bilateral vertical jumping. METHODS:Twenty athletes undergoing anterior cruciate ligament reconstruction and twenty healthy athletes,aged 20-24 years,were recruited in Wuhan Sports University from December 2021 to December 2022.All the 40 subjects underwent a bilateral vertical jumping test.The kinematic and dynamic characteristics of the lower limbs at propulsion phase,initial landing time and peak vertical ground reaction force moment. RESULTS AND CONCLUSION:At the initial landing time,the athletes undergoing anterior cruciate ligament reconstruction showed higher hip flexion angle(P=0.031)and lower ankle plantar flexion angle(P=0.018)on the operated side compared with the healthy athletes.At the peak vertical ground reaction force moment,the athletes undergoing anterior cruciate ligament reconstruction had higher hip flexion angle(P=0.016),lower hip abduction angle(P=0.019),lower knee flexion angle(P=0.025),higher knee external rotation angle(P=0.030),and higher ankle external rotation angle(P=0.042)on the operated side compared with the healthy athletes.At the peak vertical ground reaction force moment,the athletes undergoing anterior cruciate ligament reconstruction showed lower knee extension moment(P=0.036),lower knee internal rotation moment(P=0.016),lower hip abduction moment(P=0.004),higher hip extension moment(P=0.040),and higher hip external rotation moment(P=0.005)on the operated side compared with the healthy athletes.To conclude,the athletes undergoing anterior cruciate ligament reconstruction exhibit a stiff landing pattern,in which the knee load on the operated side tends to shift to the hip joint,and show inadequate control of lower limb rotational stability.Therefore,detection and correction of abnormal biomechanical characteristics should be part of the rehabilitation after anterior cruciate ligament reconstruction.
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Objective:To compare the efficacy and safety of Castor single-branch stent and in vitro fenestration stent in treating thoracic aortic diseases with insufficient landing zone.Methods:The clinical data of patients with thoracic aortic diseases treated with Castor single-branch stent or in vitro fenestrated stent between December 2017 and June 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. A total of 184 patients were included, 99 patients were treated with Castor branch stent, and 85 patients with in vitro fenestration stent. All patients′ general clinical data, surgical data, perioperative and follow-up clinical and imaging data, and postoperative complications were collected. The χ2 test was used to compare the incidence of complications between the two groups, and the Kaplan-Meier method was used to plot the survival rate without adverse events between the two groups. Results:Stent placement was successful in all patients, and the success rate of the technique was 100%. Other branches were reconstructed in 2 patients in the Castor group and double fenestrated stent were reconstructed in 12 patients in the fenestrated group. The mean operation time of the Castor group was significantly shorter than that of the fenestrated group, the number of patients who received local anesthesia was significantly lower than that of the fenestrated group, and the endoleak rate during follow-up was significantly lower than that of the fenestrated group ( P<0.05). There was no significant difference in the postoperative hospital stay, the incidence rate of perioperative complications, mortality, the incidence rate of neurological complications, new dissection or aneurysm rate, branch stent stenosis rate, second surgical intervention rate, and false lumen thrombosis between the two groups ( P>0.05). The adverse event-free survival rate of the Castor group was slightly higher than that of the fenestrated group, but its difference was not statistically significant ( P>0.05). Conclusion:Castor branch stent and in vitro fenestration stent have good short-term and mid-term efficacy in the treatment of aortic diseases with insufficient landing zone, which are safe and effective options for reconstruction of LSA and other branch arteries.
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AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.
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Objective:The aim of this study was to evaluate the in vitro activity of lysosin-Ⅰ against Methicillin-resistant Staphylococcus aureus (MRSA) and its synergistic effect with eight common antibacterial drugs against MRSA. Methods:This study was conducted following the design principles of a randomized controlled trials. Ten MRSA isolates, clinically isolated from the Second Xiangya Hospital of Central South University between September and November 2021, were determined the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bactericidal kinetic test of lycosin-Ⅰ in vitro anti-MRSA by micro-broth dilution method. Additionally, the micro-broth chessboard dilution method was utilized to evaluate the in vitro efficacy of lycosin-Ⅰ in combination with eight common antimicrobial agants, including penicillin, erythromycin, levofloxacin, gentamicin, rifampicin, minocycline, vancomycin, and linezolid. Results:The MIC range of lycosin-Ⅰ against MRSA was found to be between 4-8 mg/L with the MIC 50 and MIC 90 were 4 mg/L and 8 mg/L, respectively. The range of MBC was also between 4-8 mg/L, and the ratio of MBC/MIC was 1-2. The bactericidal kinetics test revealed that the number of surviving MRSA clinical isolates and standard strains initially decreased rapidly but then showed a resurgence when the concentration of lycosin-Ⅰ was 1/2 MIC or MIC. While, the bacterial load gradually reduced until complete elimination when the concentration was at 2 MIC or 4 MIC. The combination of lycosin-Ⅰ and gentamicin exhibited mainly synergistic effects, while the combination with other antibiotics showed mainly additive effects. Moreover, the combination of lycosin-Ⅰ and antibacterial drugs can significantly reduce the MIC 50 and MIC 90 of antibiotics. Conclusion:lycosin-Ⅰ has great antibacterial and bactericidal activity against MRSA in vitro with rapid and thorough sterilization effect and it can play a synergistic or additive role when combined with other antibacterial drugs against MRSA in vitro.
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Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.