BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

Objective To develop a machine learning model integrating preoperative chest CT radiomic features with clinical data for predicting 5-year postoperative recurrence risk in stage Ⅰ non-small cell lung cancer(NSCLC)patients undergoing surgical resection.Methods A total of 217 patients with pathologically confirmed stage Ⅰ NSCLC(selected from 778 initially screened cases based on our inclusion and exclusion criteria)treated in Army Medical Center of PLA between January 2014 and December 2019 were retrospectively enrolled,including 53 recurrence cases and 164 non-recurrence cases within 5-year follow-up.They were randomly divided into a training set(n=173)and a validation set(n=44)in a ratio of 8:2.Radiomic models were established based on extracted features from tumor-dominant regions of interest(ROI)on CT images,while clinical models were developed using demographic characteristics and preoperative laboratory examinations.A combined model was further constructed by integrating both feature sets,and model performance was compared to identify the optimal predictive model.Results This study screened the features from non-contrast CT images and ultimately selected 7 radiomic features for constructing radiomic model.Among 6 machine learning algorithms,the adaptive boosting(Adaboost)model demonstrated the best overall predictive performance,with an area under the curve(AUC)of 0.866(95%CI:0.808～0.923;accuracy:0.832,specificity:0.884)in the training set and of 0.806(95%CI:0.630～0.983;accuracy:0.795,specificity:0.971)in the validation set.Univariate and multivariate logistic regression analyses identified 4 clinical features for clinical model construction.The clinical model achieved an AUC value of 0.874(95%CI:0.821～0.928;accuracy:0.827,specificity:0.891)in the training set and 0.813(95%CI:0.677～0.948;accuracy:0.636,specificity:0.600)in the validation set.By integrating the 7 radiomic features and 4 clinical features using a feature-level fusion strategy,the combined model exhibited further improved predictive performance,with an AUC value of 0.953(95%CI:0.924～0.983;accuracy:0.884,specificity:0.860)and 0.852(95%CI:0.729～0.976;accuracy:0.682,specificity:0.629),respectively in the training set and the validation set.Conclusion The combined model integrating preoperative CT radiomic features with clinical risk factors may provide an evidence-based framework for evaluating 5-year postoperative recurrence risk in stage Ⅰ NSCLC patients.

Objective To explore the value of CT combined with MRI(hereinafter referred to as combined diagnosis)in diagnosing sacroiliac joint lesions in ankylosing spondylitis(AS).Methods A retrospective study selected CT and MRI examination data from 102 AS patients with sacroiliac joint lesions admitted to the Third People's Hospital of Haikou,Hainan Province between January 2021 and July 2023.The study compared the grading and detection rates of various signs using CT,MRI,and combined diagnosis.Results MRI showed higher detection rates for AS sacroiliac joint lesions in grades I-II,bone marrow edema,tendon and ligament attachment point inflammation,subchondral cartilage destruction,synovial thickening,and subchondral fat deposition compared to CT(P<0.05).In contrast,CT demonstrated higher accuracy in detecting joint surface sclerosis,subchondral bone erosion/destruction,and joint surface hyperplasia compared to MRI(P<0.05).Combined diagnosis showed significantly higher grading and detection rates of AS sacroiliac joint lesion signs compared to MRI or CT alone(P<0.05).Conclusion MRI has high detection rates for early AS sacroiliac joint lesions,CT exhibits high sensitivity for joint surface hyperplasia,sclerosis,erosion,and destruction,and combined diagnosis demonstrates superior efficacy compared to MRI or CT individually.

This article reviews the review articles and research papers related to biomanufacturing driven by engineered organisms published in the Chinese Journal of Biotechnology from 2023 to 2024. The content covers 26 aspects, including chassis cells; gene (genome) editing; facilities, tools and methods; biosensors; protein design and engineering; peptides and proteins; screening, expression, characterization and modification of enzymes; biocatalysis; bioactive substances; plant natural products; microbial natural products; development of microbial resources and biopesticides; steroidal compounds; amino acids and their derivatives; vitamins and their derivatives; nucleosides; sugars, sugar alcohols, oligosaccharides, polysaccharides and glycolipids; organic acids and monomers of bio-based materials; biodegradation of polymeric materials and biodegradable materials; intestinal microorganisms, live bacterial drugs and synthetic microbiomes; microbial stress resistance engineering; biodegradation and conversion utilization of lignocellulose; C1 biotechnology; bioelectron transfer and biooxidation-reduction; biotechnological environmental protection; risks and regulation of biomanufacturing driven by engineered organisms, with hundreds of technologies and products commented. It is expected to provide a reference for readers to understand the latest progress in research, development and commercialization related to biomanufacturing driven by engineered organisms.
Biotechnology/methods* ; Gene Editing ; Genetic Engineering ; Metabolic Engineering ; Protein Engineering ; Biosensing Techniques

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

The purpose of this investigation was to elucidate the clinical characteristics and genetic underpinnings of a pediatric patient with neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (NDAGSW, OMIM#617807). The affected individual, a 1-year-9-month-old male, displayed physical development retardation and distinctive facial features, notably periorbital puffiness, upward-gazing palpebral fissures, a shortened philtrum, a tented mouth, and conical-shaped digits. Clinically, the patient presented with profound global developmental retardation, marked language deficits, hypotonia, and an ataxic gait. Subtle, non-diagnostic alterations were identified in cranial magnetic resonance imaging and visual evoked potential assessments. The trio-whole exome sequencing analysis revealed a de novo heterozygous mutation, c.202G>A (p.A68T), within the RAB11B gene, a known pathogenic variant linked to NDAGSW. Neurodevelopmental disorders due to RAB11B gene variants are rare disorders with clinical manifestations of severe mental retardation, aphasia, motor retardation, gait abnormalities with peculiar phenotypical features, structural abnormalities of the brain, and reduced cerebral white matter, cerebellar hypoplasia, and hypoplasia of the corpus callosum as seen on cranial imaging. Based on the characteristics of the disease, the heterozygous missense mutation c.202G>A (p.Ala68Thr) in the RAB11B gene was identified as the genetic etiology of the child.

Objective:To investigate the clinical effectiveness of autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture in the treatment of anterior cruciate ligament (ACL) tears.Methods:A retrospective study was conducted to analyze the clinical data of 38 patients with ACL tear who had been admitted to Department of Sports Medicine, The Fourth Hospital of Wuhan from January 2016 to July 2020. There were 30 males and 8 females, with an age of (25.4±7.2) years. By the typing of MRI Sherman tear locations (MSTL) for anterior cruciate ligament, 7 cases were Type I and 31 cases type II. A total of 18 patients underwent single bundle reconstruction of autologous hamstring tendon combined with remnant suture (group A), and the other 20 patients underwent conventional reconstruction to clean the synovial sheath of ACL (group B). The operation time,Tenger scores, Lysholm scores, International Knee Documentation Committee (IKDC) subjective score and side-to-side differences in relaxation at pre- operation, 1 year and 2 years after operation, as well as ACL healing of the affected knee at 2 years after operation, were observed and compared between the 2 groups. The graft synovial coverage was evaluated by secondary arthroscopy in some cases.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (38.5±8.4) months. No surgical site infection or knee stiffness occurred in the 2 groups after operation, and 2 patients in each group developed intermuscular venous thrombosis at a lower limb. There was no significant difference in operation time between the 2 groups ( P>0.05). There were significant differences in Tenger score [(6.3±1.6) points versus (4.7±1.7) points], Lysholm score [(93.4±4.2) points versus (85.9±4.3) points] and IKDC subjective score [(89.1±2.9) points versus (81.2±2.9) points] between group A and group B at 1 year after operation ( P<0.05), but there was no significant difference in Tenger score, Lysholm score or IKDC subjective score between the 2 groups at 2 years after operation ( P>0.05). There was no significant difference in side-to-side difference in relaxation between the 2 groups at 1 year or 2 years after operation ( P>0.05). MRI evaluation at 2 years after operation showed no recurrent rupture or no sign of impingement between the graft and the intercondylar fossa in either group. Conventional secondary arthroscopy for 2 patients in group A and 3 patients in group B revealed better synovial coverage in group A. Conclusion:In the treatment of ACL tears of MSTL types I and II, compared with conventional reconstruction to clean the synovial sheath of ACL, autologous hamstring tendon reconstruction with preserved synovial sheath combined with remnant suture can lead to better functional recovery at 1 year after operation, though there is no significant difference in function at 2 years after operation.

Sleep disorders is one of the most frequent and severe complications in patients with tinnitus and is highly correlated with the severity of tinnitus.Sleep disorders and tinnitus influence each other,forming a vicious circle.While in-terventions have been developed to alleviate tinnitus distress,these interventions are usually not effective in improving sleep in patients with tinnitus and sleep disorders.Helping tinnitus patients to resolve sleep disorders is the key to breaking the cycle and improving their quality of life.In this narrative review,we studyed the current state of research on sleep disorders in patients with tinnitus through three aspects:epidemiology,physiological and psychological mechanisms,and existing psychological,physical,and pharmacological interventions,and to provide a basis for further research on the relationship between tinnitus and sleep disorders and the precise treatment of tinnitus.

BACKGROUND:Chronic rotator cuff injury is often companied by tendon degeneration and impaired function of tendon-derived stem cells.As am important cytokine,platelet-derived growth factor-DD has a regulatory effect on the proliferation and differentiation of tendon-derived stem cells.OBJECTIVE:To investigate the effect of platelet-derived growth factor-DD on the proliferation and multilineage differentiation of tendon-derived stem cells in human chronic rotator cuff injury.METHODS:Tendon-derived stem cells were isolated from human chronic rotator cuff injury tissue and cultured in vitro.Immunofluorescence staining was used to observe the cytoskeletal morphology of tendon-derived stem cells.Flow cytometry was used to identify the phenotype of tendon-derived stem cells.Tendon-derived stem cells were divided into two groups.The control group did not receive any intervention.The platelet-derived growth factor-DD group was treated with 5 μg/mL platelet-derived growth factor-DD.The effect of platelet-derived growth factor-DD on the proliferation and multilineage differentiation of tendon-derived stem cells was evaluated by cell proliferation assay and three-lineage differentiation assay.RESULTS AND CONCLUSION:(1)The number of EdU-positive cells in the platelet-derived growth factor-DD group was significantly increased compared with the control group(P＜0.05).Tendon-derived stem cells entered the rapid proliferation phase earlier,and the cell growth was logarithmic.(2)The positive areas of Oil Red O staining,Alcian Blue staining,and Alizarin Red staining in the platelet-derived growth factor-DD group were significantly larger than those in the control group(P＜0.05).(3)The above results show that platelet-derived growth factor-DD significantly promotes the proliferation and adipogenic,osteogenic,and chondrogenic differentiation of tendon-derived stem cells.