Actinomycetes are important producers of high-value natural products, and the engineering of actinomycetes to enhance the biosynthesis of target natural products has long been a hot research topic in the scientific community. However, non-rational engineering methods suffer from low beneficial mutation rates, which limit the efficiency of mutant screening. The integration of high-throughput screening (HTS) technologies can effectively enhance the screening efficiency of elite mutants and significantly shorten the cycle of actinomycete strain engineering. This review comprehensively discusses various HTS technologies suitable for the engineering of actinomycete strains and compares them in terms of application scenarios, advantages, and disadvantages. HTS technologies include microplate-based screening, antimicrobial activity screening, antibiotic resistance screening, fluorescence-activated cell sorting (FACS), and fluorescence-activated droplet sorting (FADS). Additionally, this review summarizes the applications of these technologies in assisting actinomycete strain engineering and enhancing the yields of target compounds. The development and application of HTS technologies have not only facilitated the exploration of natural product resources in actinomycetes but also provided strong support for the rapid and efficient construction of high-performance engineered actinomycete strains.
Actinobacteria/metabolism* ; High-Throughput Screening Assays/methods* ; Genetic Engineering/methods* ; Biological Products/metabolism* ; Flow Cytometry ; Metabolic Engineering/methods*

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans ; Drugs, Chinese Herbal/pharmacology* ; Liver Diseases/drug therapy* ; Antioxidants ; Polysaccharides/therapeutic use* ; Medicine, Chinese Traditional

Objective:To investigate the cognitive function and its influencing factors among residents in Qingdao city.Methods:The 5 311 research subjects over 65 years old were selected from Qingdao by simple random sampling and stratified sampling. All subjects were investigated by AD8 dementia early screening questionnaire and community screening instrument dementia (CSI-D) to evaluate the prevalence of cognitive decline in this study.The score of AD8 dementia early screening questionnaire ≥2 points or the score of CSI-D ≤7 points was considered to be cognitive decline. Mann-Whitney U test, Chi-square test, Fisher exact probability method, univariate and multivariate Logistic regression analysis and Bootstrap verification were performed using SPSS 26.0 software. Results:Among 5 311 subjects, 1 899 subjects had normal cognitive function (35.76%) and 3 412 subjects had cognitive decline (64.24%). The age of the cognitive decline group was significantly higher than that of the normal group ( P<0.01). There were significant differences in gender, educational level, rural residents, marital status, chronic medical history, hypertension, rheumatoid arthritis, cerebrovascular disease, intervertebral disc disease, ischemic heart disease, monthly household income and alcohol consumption between the two groups (all P<0.05). Univariate Logistic regression analysis showed that female ( β=0.313, OR=1.367, 95% CI=1.221-1.530), age ( β=0.052, OR=1.053, 95% CI=1.043-1.063), rural residents ( β=0.850, OR=2.340, 95% CI=2.042-2.682), widowed ( β=0.557, OR=1.745, 95% CI=1.500-2.029), chronic medical history ( β=0.290, OR=1.336, 95% CI=1.191-1.498), hypertension ( β=0.134, OR=1.143, 95% CI=1.020-1.281), rheumatoid arthritis ( β=0.458, OR=1.581, 95% CI=1.222-2.046), cerebrovascular disease ( β=0.584, OR=1.794, 95% CI=1.352-2.380), intervertebral disc disease ( β=0.578, OR=1.782, 95% CI=1.370-2.319), ischemic heart disease ( β=0.501, OR=1.651, 95% CI=1.272-2.143) were the risk factors for cognitive decline. Higher education level, higher monthly household income and abstinence ( β=-0.244, OR=0.783, 95% CI=0.619-0.992) were protective factors for cognitive decline. Multivariate logistic regression analysis showed that age ( β=0.035, OR=1.036, 95% CI=1.025-1.047), rural residents ( β=0.215, OR=1.239, 95% CI=1.047-1.468), chronic medical history ( β=0.191, OR=1.210, 95% CI=1.067-1.372), cerebrovascular disease ( β=0.480, OR=1.616, 95% CI=1.195-2.187), intervertebral disc disease ( β=0.456, OR=1.578, 95% CI=1.190-2.094) were risk factors for Alzheimer's disease. Higher education level and higher monthly household income were protective factors for Alzheimer's disease. Conclusion:The elderly with chronic diseases, low income and low education level may be at the high risk of cognitive function decline, which should be paid attention to in early screening and intervention.

Objective To observe the value of the scoring model of MRI features for predicting proliferative hepatocellular carcinoma(HCC).Methods Data of 241 patients with pathologically confirmed HCC,including 90 cases of proliferative HCC and 151 cases of non-proliferative HCC were analyzed retrospectively.Univariate and multivariate logistic regression were used to compare the clinical and MRI findings evaluated according to liver imaging reporting and data system version 2018 between groups.The independent predictive factors of proliferative HCC were screened,and scores were assigned according to the weight,then a scoring model was constructed.Receiver operating characteristic(ROC)curve was drawn,and the area under the curves(AUC)were calculated to assess the predictive efficacy of this model.The patients were divided into high and low proliferation risk subgroups based on the optimal score thresholds.The recurrence free survival(RFS)rates and early RFS rates were compared between groups and subgroups.Results MRI showed tumor corona enhancement,arterial phase annular hyper-enhancement,intratumoral vessels,much focus parenchymal low enhancement and irregular tumor margins were all independent predictive factors for proliferative HCC(OR=3.287,2.362,4.542,2.997,2.379,all P＜0.05),which were then were scored with 7,5,9,7 and 5,respectively,with a total score of 0-33.AUC of the obtained scoring model for predicting proliferative HCC was 0.818.Taken 9 points as the optimal score thresholds,97 cases were assigned into high proliferation subgroup and 144 into low proliferation risk subgroups).Significant differences of RFS rates and early RFS rates were found between groups and subgroups(all P＜0.05).Conclusion MRI features scoring model could effectively predict proliferative HCC.

Purpose To investigate the pathological characteristics of hepatocellular carcinoma(HCC)with irregular rim-like arterial phase enhancement(IRE)using gadoxetic acid-enhanced,and its early recurrence prognostic significance after surgery.Materials and Methods This retrospective study included 131 patients with surgically confirmed HCCs who underwent gadoxetic acid-enhanced MRI from February 2015 to September 2021 in the Third People's Hospital of Nantong.According to the enhancement pattern of gadoxetic acid-enhanced MRI in arterial phase,HCC were divided into IRE-HCC and non-IRE-HCC.Clinical,pathological and imaging characteristics were compared between IRE-HCC and non-IRE-HCC.Logistic regression analyses were performed to identify clinical,pathological and imaging features associated with IRE-HCC.Early recurrence(within 2 years)was evaluated by using Kaplan-Meier analysis.Cox regression analysis was performed to determine independent predictors of early recurrence.Results Cytokeratin 19(CK19)(OR=9.027,95%CI 2.533-32.170,P=0.001),microvascular invasion(OR=3.606,95%CI 1.024-12.701,P=0.046)and diffusion weighted imaging target signs(OR=10.370,95%CI 3.046-35.303,P=0.000)were independent predictors for IRE-HCC.The 2-year cumulative recurrence-free survival rate postoperative of IRE-HCC was 24.1%,which was significantly shorter than that of non-IRE-HCC(55.9%,χ2=19.971,P=0.000).Microvascular invasion(HR=2.206,95%CI 1.152-4.226,P=0.017)and IRE(HR=2.454,95%CI 1.408-4.275,P=0.002)were independent predictors of early postoperative recurrence of HCC.Conclusion IRE-HCC are associated with CK19,microvascular invasion and diffusion weighted imaging target signs,and have a high recurrence rate and poor prognosis in the early postoperative period.

Objective:To analyze the hepatobiliary phase (HBP) image manifestation classification and pathological features of nodules in nodules accompanied by hepatocellular carcinoma (NIN-HCC).Methods:Twenty-five cases cases (27 lesions) with cirrhosis who were confirmed as NIN-HCC by surgical pathology and underwent gadoxetate disodium-enhanced MRI examination before surgery at Nantong Third Hospital affiliated with Nantong University from July 2015 to November 2022 were retrospectively enrolled. The size, signal intensity, enhancement pattern, and pathological features of internal and external nodules were analyzed in NIN-HCC. The lesions score were recorded according to the 2018 version of the Liver Imaging Reporting and Data Systems (LI-RADS) classification criteria. NIN-HCCs were grouped and typed according to the different HBP signal intensities of the inner and outer nodules. The independent-samples t-test, Mann-Whitney U test or Fisher's exact probability method were used to compare the differences in imaging features and LI-RADS scores between the groups. The Spearman correlation coefficient was used to evaluate the correlation between the pathological differentiation degree of internal and external nodules and the HBP signal intensity. The Kaplan-Meier curve was used to analyze recurrence-free survival (RFS) following NIN-HCC surgery. Results:The internal nodules of the 27 NIN-HCCs showed altered hypervascularity with a maximum diameter of (13.2±5.5) mm during the arterial phase. 51.9% (14/27) and 48.1% (13/27) showed "fast in and fast out" and fast in and slow out"enhancement patterns. The external nodules showed altered hypovascularity with a maximum diameter of (25.7±7.3) mm, and 13 (48.1%) of them were accompanied to manifest during the arterial phase. NIN-HCC was divided into two groups according to the signal intensity of HBP of the outer nodules with the background liver parenchyma signal intensity as a reference: the hyposignal group ( n=17, 63.0%) and the isosignal group ( n=10, 37.0%). The hyposignal group and the isosignal group were divided into A~C type and D~F type, a total of six types, according to the hypo, iso, and hyper signals of the inner nodules and the signal intensity of the outer nodules as a reference. Within the hyposignal group, 7.4% (2/27) of the inner nodules showed hyposignal (type A), 37.0% (10/27) showed isosignal (type B), and 18.5% (5/27) showed hypersignal (type C). Within the isosignal group, 29.6% (8/27) of the inner nodules showed hyposignal (type D), 7.4% (2/27) showed isosignal (type E), and there was no hypersignal (type F). 40.7% (11/27) of the lesions were LR-4 in LI-RADS score, and 59.3% (16/27) were LR-5. There was no statistically significant difference ( P>0.05) in the maximum diameter, enhancement pattern, and LI-RADS score of internal and external nodules between the hypo and iso signal group. Histologically, NIN-HCC showed fine trabecular/pseudoglandular duct type without microvascular invasion, among which the inner nodules were mainly moderately differentiated HCC, and the outer nodules were mainly well-differentiated HCC. The degree of differentiation between the inner and outer nodules and the HBP signal intensity had no statistically significant difference ( r=0.290, P=0.143; r=0.079, P=0.697). The median RFS follow-up time after NIN-HCC radical resection was 31.7 months, and the cumulative RFS rates at 1, 3, and 5 years were 96.0%, 76.0%, and 64.0%, respectively. Conclusions:NIN-HCC can serve as a morphological marker for early-stage diagnosis of multi-step cancer evolution in HCC, with certain imaging and pathological features. HBP imaging classification is helpful to enhance the diagnostic recognition of this disease.

Objective To evaluate the clinical efficacy of kissing-stent implantation in the treatment of chronic iliac-vena cava occlusion.Methods The clinical data of 22 patients with chronic iliac-vena cava occlusion,who received kissing-stent implantation,were retrospectively analyzed.The surgical success rate and the procedure-related complications were recorded,the postoperative 3-,6-and 12-month stent patency rates were calculated,and the postoperative 6-month Villalta score was compared with its preoperative value.Results The technical success rate of kissing-stent implantation was 100％.No procedure-related surgical complications occurred.The postoperative 3-,6-and 12-month stent patency rates were 95.5％,90.9％and 86.1％respectively.The postoperative 6-month Villalta score was(12.14±2.80)points,which was remarkably lower than preoperative(20.91±3.16)points,the difference was statistically significant(P＜0.05).Conclusion The implantation of kissing-stent can successfully reconstruct iliac-vena cava with satisfactory short-term efficacy for chronic iliac-vena cava occlusion.

Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.

Objective To investigate the value of the liver imaging reporting and data system v2018(LI-RADS v2018)and other imaging features in predicting preoperative risk and postoperative prognosis of isolated macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Patients with isolated hepatocellular carcinoma(HCC)confirmed by pathology after preoperative MRI examination were selected,and all patients were randomly assigned to a training group(n=146)and a validation group(n=62)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were used to screen independent prognostic factors of MTM-HCC and construct a nomogram.Patients were stratified into high-risk and low-risk subgroups based on the nomogram scores.Kaplan-Meier survival curves and Log-rank tests were used to compare the recurrence-free survival(RFS)among different subgroups of patients.Results Multivariate logistic regression analysis revealed that intratumoral vessels[odds ratio(OR)=3.480,95％confidence interval(CI)1.110-10.912,P=0.032],arterial phase hypovascular component ≥20％(OR=4.615,95％CI 1.728-12.321,P=0.002),and corona enhancement(OR=4.814,95％CI 1.816-12.766,P=0.002)were independent predictors of MTM-HCC.The nomogram constructed based on these indicators demonstrated area under the curve(AUC)of the receiver operating characteristic(ROC)curve was 0.834 and 0.764 for predicting MTM-HCC in the training and validation groups,respectively.The RFS predicted by the nomogram was significantly different between the high-risk and low-risk subgroups and both the pathologically confirmed MTM-HCC positive and negative groups(P＜0.05).Conclusion Intratumoral vessels,arterial phase hypovascular component ≥20％,and corona enhancement are independent predictors of MTM-HCC.The constructed nomogram based on these predictors demonstrates good diagnostic efficacy for MTM-HCC and has significant prognostic value for patients'RFS.