BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Objective:To analyze the application value of color Doppler ultrasound,microribonucleic acid-19a(miR-19a)and miR-210 in carotid artery stenosis.Methods:A total of 102 patients with carotid artery stenosis who were diagnosed and treated in Cangzhou People's Hospital from October 2020 to October 2022 were selected as the research group,and 102 health persons who underwent color Doppler ultrasound of physical examination in hospital at the same period were selected as the health control group.Both two groups underwent color Doppler ultrasound examination and digital subtraction angiography(DSA)within one week after admitted to hospital.The miR-19a and miR-210 between the two groups were compared,and the miR-19a and miR-210 of patients with different stenosis degrees of research group also were compared.And then,the diagnostic values of color Doppler,miR-19a,miR-210 and the combination of them were analyzed in diagnosing carotid artery stenosis.Results:The results of color Doppler ultrasound in detecting common carotid artery 102 patients of research group indicated that 15 cases were normal,and 15 cases occurred mild stenosis,and 21 cases occurred moderate stenosis,and 21 cases occurred severe stenosis and 33 cases occurred complete occlusion.The miR-19a of the research group was significantly higher than that of the health control group,and the miR-210 of the research group was significantly lower than that of the health control group(t=10.755,-5.903,P<0.05).The miR-19a results of the research group indicated that the miR-19a of mild stenosisthat of moderate stenosis>severe stenosis>complete occlusion,and the differences were statistical significant(F=160.399,147.462,P<0.05),respectively.The receiver operating characteristic(ROC)curve analysis showed that the area under curve(AUC)values of color Doppler ultrasound,miR-19a,miR-210 and combined diagnosis of them for carotid artery stenosis were respectively 0.892,0.842,0.729 and 0.978,and the sensitivity and specificity of the combined diagnosis were respectively 97.1%and 95.1%.Conclusion:The combined diagnosis of color Doppler ultrasound,miR-19a and miR-210 has higher diagnostic value for carotid artery stenosis.

Objective To analyze and identify the volatile constituents in different parts(flowers,stems and leaves)of Huai chrysanthemumin,and to lay a theoretical foundation for the comprehensive utilization for it.Methods The volatile oil in different parts of Huai chrysanthemumin were extracted by hydrodistillation,respectively.Their constituents were analyzed by gas chromatography-mass spectrometry(GC-MS).The compounds were identified by library search and literature screening.The relative percentage of each compound was obtained by the area normalization method.The differences in their chemical compositions were analyzed by Venn diagram,principal component analysis(PCA)and cluster heat map analysis.Results A total of 62 volatile chemical components were identified from different parts of Huai chrysanthemumin,including monoterpenes,sesquiterpenes,and their derivatives,as well as a small amount of aliphatic compounds.32,42 and 40 volatile components were detected from the flowers,stems and flowers,respectively.Furthermore 17 volatile components were shared by three parts,whereas 5,6 and 16 volatile components were unique to the flowers,stems and leaves,respectively.The results of stoichiometric analysis showed that both PCA and cluster heat map analysis could separate the flowers,stems and leaves,and their volatile components were different.Conclusion The types and contents of the volatile oil in the stems,leaves and flowers of Huai chrysanthemumin have certain variability,which provide a scientific basis for the further medicinal or industrial exploitation of different parts of Huai chrysanthemumin.

Background Bacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. Objective To understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. Methods Three subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO₂), fine particulate matter (PM_2.5), and inhalable particulate matter (PM₁₀) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min⁻¹, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO₂ concentration and total bacterial count. Results The pass rates were 100.0% for airborne total bacteria count, PM_2.5, and PM₁₀ in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO₂, but 0% for humidity. The overall median (P₂₅, P₇₅) total bacteria count was 177 (138,262) CFU·m⁻³. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P<0.05). A total of 874 strains and 82 species were identified by automatic microbial mass spectrometry. The results of identification were all over 9 points, and the predominant bacteria in the air were Micrococcus luteus (52.2%) and Staphylococcus hominis (9.8%). Three pathogens, Acinetobacter baumannii (0.3%), Corynebacterium striatum (0.1%), and Staphylococcus epidermidis bacilli (2.2%) were detected in 23 samples (2.6%), and the associated locations were mainly distributed in train compartments during evening rush hours. Conclusion The total bacteria count in indoor air varies by monitoring sites of subway stations and time periods, and there is a risk of opportunistic bacterial infection. Attention should be paid to cleaning and disinfection during peak passenger flow hours in all areas.

Objective:Diabetic retinopathy (DR) has been reported as the leading cause of blindness among diabetic adults, which is closely related to poor quality of life and increased burden of disability. This study aimed to aggregate the optimally available evidence on modifiable risks of DR.Methods:Until June 2023, PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analysis about various risk factors for DR, and Meta-analysis were analyzed and summarized. R 4.3.2 software was used for each Meta-analytic association to calculate the effect size, 95% CI, heterogeneity, small-study effects, excess significance bias, and 95% prediction intervals. The credibility of significant evidence was graded. Results:We captured 23 eligible papers (72 associations) covering a wide range of medication use, concomitant diseases, daily intervention, biomarkers, lifestyle, and physical measurement index. Among them, higher HbA1c variability ( RR=1.45, 95% CI: 1.26-1.66) and urine microalbumin positive ( OR=2.44, 95% CI: 1.99-2.97) were convincing (grade Ⅰ) evidence, and insulin use ( RR=3.48, 95% CI: 2.14-5.67) was highly suggestive (grade Ⅱ) evidence. Moreover, hypertension ( OR=2.03, 95% CI: 1.06-3.97), poor glycemic control ( OR=4.35, 95% CI: 1.47-12.85), positive macroalbuminuria ( OR=8.42, 95% CI: 3.52-20.15), long sleep duration ( OR=2.05, 95% CI: 1.37-3.05), vitamin D deficiency ( OR=2.02, 95% CI: 1.17-3.50), periodontitis ( OR=4.51, 95% CI: 1.76-11.55) were the main risk factors for DR. Intensive blood pressure intervention ( RR=0.78, 95% CI: 0.65-0.94), dietary control ( OR=0.64, 95% CI: 0.47-0.89) and moderate intensity physical activity ( RR=0.76, 95% CI: 0.59-0.97) yielded significant protective associations with DR. Conclusions:Intensive blood pressure glycemic control, and a healthy lifestyle pattern could reduce the risk of DR. This study provides the evidence to identify high-risk populations and recommends rational treatment options and healthy living interventions.

Objective:To explore the clinical and electrophysiological characteristics of flail arm syndrome (FAS).Methods:Clinical and electrophysiological data were collected on 13 FAS patients and 31 persons with upper limb onset amyotropic lateral sclerosis (UL-ALS), including the amplitude of compound muscle action potential (CMAP) related to median nerve, ulnar nerve, and axillary nerve motor conduction. A split-hand index (SI) was calculated by dividing the CMAP amplitude of abductor pollicis brevis by that of the abductor digiti minimi. Clinical features, the CMAP amplitudes and SIs were compared between the FAS and UL-ALS patients.Results:Compared with UL-ALS patients, the age at onset among the FAS patients was older (averaging 60.9 years). The development to the second stage was longer (24±6 months). The upper limb reflexes of 15% of the FAS patients had disappeared and those of 77% were weakened, while the lower limb reflexes of 54% of the FAS patients were active and 38% were weakened, significantly different from the UL-ALS patients. However, there were no significant differences in the CMAP amplitudes of the median and ulnar nerves, nor in SI between the FAS and UL-ALS patients. The SIs of the FAS patients with upper motor neuron signs were significantly lower than those of FAS patients without such signs. Among the FAS patients, the average CMAP amplitude of the ulnar nerve was the highest, followed by those of the median and axillary nerves. Among the UL-ALS patients, however, the average CMAP amplitude of the ulnar nerve was not significantly different from that of the axillary nerve.Conclusions:FAS patients with upper motor neuron signs are more likely to have slip hand. The CMAP amplitude of their axillary nerve tends to be lower than that of their median and ulnar nerves. FAS seems to be a special type of ALS.

Objective To report the clinical features, myopathological changes, and gene mutations in five Chinese patients with mitochondrial diseases caused by POLG gene mutations. Methods Clinical materials of five unrelated patients who were referred to Department of Neurology, Peking University First Hospital from April 2012 to January 2018, carrying POLG gene mutations, were retrospectively analyzed. Muscle/nerve biopsies and targeted second-generation gene sequencing were performed on the patients. Results Among the five patients, three were male and two were female. Two cases were dominant inheritance and three were sporadic or recessive inheritance. The ages of onset were from 15 to 40 years with disease course of one to 26 years. One of them showed atypical SANDO (sensory ataxic neuropathy, dysarthria, and ophthalmoparesis) syndrome accompanied by cardiac preexcitation syndrome. There were two cases with autosomal dominant and one case with recessive progressive external ophthalmoplegia plus syndrome. One case presented with cognitive delay and sensory neuropathy. The pathological changes of mitochondrial myopathy were observed in all four patients with muscle involvement. Sural nerve biopsy in the patient with cognitive delay and sensory ataxia revealed chronic axonal pathological changes. POLG gene mutations were found in all five patients by targeted next generation sequencing, including single heterozygous mutations in two dominant inherited patients (c. 914 G＞A and c. 2864A＞G, respectively), and compound heterozygous POLG gene mutations in the other three sporadic/recessive inherited patients (c. 2591 A＞G/c. 1790 G＞A, c. 924G＞T/c. 3002delG and c. 1613A＞T/c. 1612 G＞T, respectively). There were six novel mutations not reported before, i.e., c.914G＞A(p.S305N), c.924G＞T(p.Q308H), c.1613A＞T(p.E538V), c.1612G＞T(p.E538*), c.1790 G＞A(p.R597Q) and c.3002delG. Conclusions POLG gene mutations can lead to different clinical spectrums. Progressive external ophthalmoplegia, limb weakness and axonal sensory neuropathy are common presentations in this group of patients with POLG gene related mitochondrial neuromuscular diseases. Novel mutations found in this study expand the mutational spectrum of POLG gene.

Objective: To analyze the prognostic factors and the value of radiotherapy (RT) for the early stage (T_1-2N₁M₀) triple-negative breast cancer (TNBC) patients after modified radical mastectomy, and provide a basis for the selection of the clinical treatment strategy. Methods: The retrospective analysis was performed in 87 TNBC patients at T_1-2N₁M₀ stage. All patients were admitted to the Second Affiliated Hospital of Dalian Medical University from Jan 2006 to Oct 2011. Fifty-three cases received postoperative RT (RT group), and the other 34 cases without RT (non-RT group). Factors enrolled in Kaplan-Meier analysis were postoperative RT, age, menstruation, histological grade, vascular tumor thrombus, T staging, the number of positive lymph node and metastasis rate, surgery procedure, Ki-67 index. The endpoints were local regional recurrence rate (LRR), distant metastasis rate (DM), recurrence free survival (RFS), and overall survival (OS) rate for 5 years. Results: The significant difference was found in the 5-year LRR (9.4% vs. 15.2%) and RFS (81.3% vs. 66.7%) between RT group and non-RT group (χ²=8.073, 12.789, P<0.05). No significant difference in the DM and OS was observed between the two groups (P>0.05). The univariate analysis showed that RT, lymph node metastasis, age, and Ki-67 index were the risk factors for 5-year LRR (P<0.05), while vascular thrombus and lymph node metastasis rate were risk factors for 5-year DM (P<0.05), RT, vascular tumor thrombus, lymph node metastasis rate, and Ki-67 index 5-year RFS (P<0.05). The multivariate analysis showed that RT and lymph node metastasis were the independent risk factors for 5-year LRR (HR=0.279, 5.277, P<0.05), vascular thrombus was an independent risk factor 5-year DM (HR=2.313, P<0.05), while RT, vascular tumor thrombus and lymph node metastasis rate were the independent risk factors for 5 years RFS (HR=0.378, 2.350, 5.084, P<0.05). Conclusions Postoperative RT might improve the local control rate of TNBC patients at T_1-2N₁M₀ stage, while the effect on DM and OS in 5 years was little. Postoperative RT, lymph node metastasis rate, vascular tumor thrombus, Ki-67 index and age are related to patient′s prognosis of early stage TNBC.

Objective To investigate the effect of clinical pathway on inpatients for rehabilitation. Methods The hospital expense, the ex-pense for medicine and length of stay in hospital were compared in patients with cerebral hemorrhage, cerebral infarction, spinal cord injury and spastic cerebral palsy before (January 1st, 2012 to April 30th, 2013) and after (May 1st, 2013 to December 31st, 2015) clinical pathway implementation, 50 inpatients for each disease, totally 200 patients. Results The length of stay in hospital reduced after of clinical pathway implementation, in all the diseases (t>5.226, P<0.001), with the decrease of hospital expense for cerebral infarction (t=3.327, P<0.001). There was no significant increase in any expense in the disease (t<1.777, P>0.05). Conclusion The implementation of rehabilitation clinical pathway can reduce the length of stay in hospital for the patients rehabilitation in hospital, without increasing their cost.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.