OBJECTIVES: To investigate the expression of the long non-coding RNA maternally expressed gene 3 (LncRNA Meg3) in patients with the Wilson disease (WD) and its correlation with the severity of liver fibrosis and autophagy-related markers. METHODS: A total of 100 WD patients and 50 healthy individuals were enrolled from the First Affiliated Hospital of Anhui University of Chinese Medicine. Serum biomarkers, including platelet count, hyaluronic acid (HA), laminin (LN), type III procollagen N-terminal peptide (PIIINP), type IV collagen (C‑IV), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were measured, and the non-invasive indices APRI and FIB-4 were calculated. Peripheral blood levels of LncRNA Meg3, Beclin-1 and LC3B were detected using RT-qPCR, and liver stiffness (LSM) and shear wave velocity (SWV) were evaluated using two-dimensional shear wave elastography (2D-SWE). The liver tissues from 10 WD patients and 10 patients with hepatic hemangioma were examined using histochemical staining, transmission electron microscopy, and RT-qPCR. RESULTS: The expression level of LncRNA Meg3 was significantly lower, while the levels of AST, ALT, HA, LN, PIIINP, C‑IV, APRI, FIB-4, LSM and SWV were significantly higher in WD patients than in the healthy individuals (all P<0.01). LncRNA Meg3 was negatively correlated with LSM, SWV, APRI, FIB-4, Beclin-1 and LC3B (P<0.05). ROC analysis demonstrated that LncRNA Meg3 effectively discriminated >F4 stage fibrosis (AUC=0.902) with a sensitivity of 92.9% and a specificity of 83.7% at the optimal cut-off value, outperforming APRI (AUC=0.746) and FIB-4 (AUC=0.661). The liver tissues from WD patients exhibited characteristic histopathological changes and lowered expression of LncRNA Meg3, which was negatively correlated with Beclin-1 and LC3B expressions (P<0.05). Liver fibrosis staging (7 S4 cases and 3 S3 cases) was significantly associated with LSM and SWV levels (P<0.05). CONCLUSIONS The expression level of LncRNA Meg3 is significantly decreased in WD patients, which is negatively correlated with the severity of liver fibrosis and closely related to the level of autophagy.
Humans ; RNA, Long Noncoding/metabolism* ; Liver Cirrhosis/metabolism* ; Adult ; Female ; Male ; Hepatolenticular Degeneration/metabolism* ; Case-Control Studies ; Young Adult ; Adolescent ; Middle Aged

Objective:To develop a wearable gait analysis system based on "Lab-in-Shoe" intelligent footwear for quantitative assessment of gait dysfunction in patients with ankle injuries.Methods:In this study, integration of inertial sensors and insole-type plantar pressure distribution sensors into footwear formed the hardware core of the "Lab-in-Shoe" intelligent footwear system. In terms of algorithms, acceleration data from the inertial sensors were integrated to obtain spatial parameters of gait. The insole-type plantar pressure sensors were employed to acquire the data concerning foot pressure distribution, as well as temporal parameters and mechanical parameters of gait, including support phase, swing phase, and zero velocity moments. To validate the accuracy of this system, 8 young and healthy participants [age: (25.6±1.3) years; height: (175.4±2.2) cm] were recruited for gait data collection in an optical motion capture laboratory. By comparing the gait data between the "Lab-in-Shoe" intelligent footwear system and the gold standard Vicon optical motion capture system, the effectiveness and reliability of the intelligent footwear system were respectively tested. Additionally, a calibration experiment was conducted for the sensing units of the plantar pressure sensors to examinate the accuracy of the pressure data.Results:The tested system accurately captured the following gait parameters of the participants: step length, step width, step frequency, walking speed, gait phase division, foot pressure distribution, and center of pressure curve, among other core spatiotemporal gait parameters. Moreover, the system demonstrated its ability to replicate the dual-foot posture during gait. Compared with the gold standard Vicon optical motion capture system through Bland-Altman, the Lab-in-Shoe smart shoe system showed stride length mean error within 3.12% (range: 2.76% to 4.24%) across 3 different walking speeds [slow speed (0.68±0.05) m/s, preferred speed (1.10±0.07) m/s, and fast speed (1.40±0.13) m/s]. 90% of the results fell within the 95% limits of agreement, indicating good consistency. The intraclass correlation coefficients (ICC) for stride parameters within the slow, preferred, and fast walking speed groups were 0.93, 0.917, and 0.893, respectively, indicating good reliability. The calibration data of multiple sensor units from the plantar pressure sensors all fell within the 95% linear regression range, with a correlation coefficient of r=0.949 ( P<0.05). The plantar pressure data collected by the intelligent footwear system presented a distinct bimodal characteristic. Conclusions:The "Lab-in-Shoe" smart shoe system developed by our institute is capable of collecting and calculating gait parameters conveniently and quickly, and demondtrates good reliability and validity across different walking speeds. Therefore, it is valueable for large-scale gait data collection in a clinical setting.

ObjectiveTo evaluate the effectiveness of Gandou decoction （GDD） by analyzing theclinical efficacy of GDD combined with speech training on the treatment of dysarthria with endoretention of damp-heat in Wilson's disease （WD）， so as to provide more clinical data and theoretical support for the selection of appropriate treatment schemes for WD patients with dysarthria with endoretention of damp-heat. MethodA total of 60 eligible WD patients with dysarthria with endoretention of damp-heat were selected and divided into a control group and a treatment group according to the random grouping method， with 30 cases in each group. The control group was treated with speech training + sodium dimercaptopropanesulfonate （DMPS）， and the treatment group was combined with GDD on the basis of the control group， with eight days as a course of treatment for 32 days. The total clinical effectiveness rate （Goldstein clinical classification）， dysarthria grading assessment from China Rehabilitation Research Center， TCM syndrome scores， 24-hour urine copper content， and modified Frenchay dysarthria rating scale scores of the two groups were compared before and after treatment. ResultAfter treatment， the total effective rate of the observation group was 90.0% （27/30）， and that of the control group was 70.0% （21/30）. The total effective rate of the observation group was significantly higher than that of the control group （Z=-1.986，P<0.05）. After treatment， the modified Frenchay dysarthria score， dysarthria grading assessment from China Rehabilitation Research Center， and 24-h urine copper in the two groups were significantly increased （P<0.05， P<0.01）， and the TCM syndrome score was significantly decreased （P<0.01）. Compared with the control group after treatment， except for the respiratory and jaw score， the modified Frenchay dysarthria score of the observation group was significantly increased （P<0.05， P<0.01）. The dysarthria grading from China Rehabilitation Research Center and 24-h urine copper content were significantly increased （P<0.01）， and the observation group had better efficacy. During the study period， there were no serious adverse reactions such as fever， rash， oral and eyelid mucosal swelling， exfoliative dermatitis， vomiting， diarrhea， or allergic shock during copper excretion treatment of DPMS and oral administration of GDD. ConclusionGDD combined with speech training can improve the symptoms and efficacy of WD patients with dysarthria with endoretention of damp-heat and enhance the patients' living standard to a certain extent， which can be widely used in clinics.

Objective To explore the antioxidant capacity of the volatile oil components of the Mongolian medicine Zhenbaowan and the mechanism of action in the treatment of rheumatoid arthritis(RA)by using bioinformatics technology,GC-MS technology,and antioxidant activity experiment.Methods The volatile oil in Zhenbaowan was extracted using water vapor distillation and the volatile oil components were qualitatively analyzed by GC-MS.Based on the results of GC-MS analysis,bioinfor-matics analysis was used to investigate the main components,key targets,and pathways of the volatile oil of Zhenbaowan in pre-venting and treating RA.Meanwhile,the antioxidant activity of the volatile oil was determined and analyzed using the 2,2-Diphen-yl-1-picrylhydrazyl(DPPH)method.Results A total of 115 volatile oil components were identified in Zhenbaowan,of which the top 48 components accounted for 97.66%of the total volatile oil content.Bioinformatics analysis revealed that Zhenbaowan can regulate signal transduction,inflammation,and protein phosphorylation through 147 RA-related targets,and intervene in signaling pathways such as PI3K-Akt,MAPK,and RAS.Molecular docking results showed that the seven main components of Zhenbaowan volatile oil can spontaneously bind to the five core targets.Antioxidant activity tests have proved that the volatile oil of Zhenbaowan has a more significant antioxidant capacity.Conclusion Using GC-MS high-throughput analysis technology combined with bioinformatic analysis and antioxidant activity test,the pharmacodynamic substances and mechanism of action of the volatile oil components of Zhenbaowan,a Mongolian medicine,in the treatment of RA are hypothesized.It provides a theoretical basis for the further study of the volatile oil components of Zhenbaowan.

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Methanol has become an attractive substrate for the biomanufacturing industry due to its abundant supply and low cost. The biotransformation of methanol to value-added chemicals using microbial cell factories has the advantages of green process, mild conditions and diversified products. These advantages may expand the product chain based on methanol and alleviate the current problem of biomanufacturing, which is competing with people for food. Elucidating the pathways involving methanol oxidation, formaldehyde assimilation and dissimilation in different natural methylotrophs is essential for subsequent genetic engineering modification, and is more conducive to the construction of novel non-natural methylotrophs. This review discusses the current status of research on methanol metabolic pathways in methylotrophs, and presents recent advances and challenges in natural and synthetic methylotrophs and their applications in methanol bioconversion.
Humans ; Methanol/metabolism* ; Metabolic Engineering ; Metabolic Networks and Pathways ; Biotransformation

Objective:To explore the clinical efficacy of thermal moxibustion combined with Duhuo Jisheng Decoction in the treatment of liver and kidney deficiency syndrome of knee osteoarthritis (KOA).Methods:From January 2020 to January 2021, 124 KOA patients with liver and kidney deficiency syndrome, who met the inclusion criteria, were divided into 2 groups according to the random number table method, with 62 in each group. The control group was treated with Duhuo Jisheng Decoction, and the observation group was treated with thermal moxibustion on the basis of the control group. Both groups were treated for 28 days. TCM symptom scores were performed before and after treatment, the Osteoarthritis Index of Western Ontario and McMaster University (WOMAC) was used to evaluate joint function. ELISA was used to detect serum insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), transforming growth factor-β1 (TGF-β1), IL-1β, IL-6, TNF-α levels, and the clinical efficacy was evaluated.Results:The total effective rate was 91.9% (57/62) in the observation group and 77.4% (48/62) in the control group, and there was significant difference between two groups ( χ2=5.04, P=0.025). After treatment, the TCM symptom score and WOMAC score of the observation group were significantly lower than those of the control group ( t values were 11.33 and 12.23, respectively, all Ps<0.01). After treatment, the serum levels of IGF-1 [(15.63±2.03) ng/L vs. (12.78±1.57) ng/L, t=8.75], FGF-2 [(30.26±5.37) ng/L vs. (26.31±1.94) ng/L, t=5.45] and TGF-β1[(30.39±6.71)μg/L vs. (24.31±5.12) μg/L, t=5.67] in the observation group were significantly higher than those in the control group ( P<0.01), while the levels of IL-1β [(12.50±3.36) ng/L vs. (16.09±4.90) ng/L, t=4.76], IL-6 [(10.59±3.28) ng/L vs. (21.75 ± 4.09) ng/L, t=16.76] and TNF-α [(4.04±1.92) ng/L vs. (6.48±1.43) ng/L, t=8.03] in the observation group were significantly lower than those in the control group ( P<0.01). There was no adverse events from both groups during treatment. Conclusion:Thermal moxibustion combined with Duhuo Jisheng Ddecoction can alleviate the joint pain of KOA patients with liver and kidney deficiency syndrome, promote cartilage repair and improve the clinical curative effect.

Objective To propose a human-machine coupling dynamics modeling method based on virtual muscles, so as to quantitatively analyze the characteristics of human-computer interaction force and muscle activation of the musculoskeletal system. Methods First, in the gait experiment of wearing exoskeleton, the human motion capture system and self-developed mechanical monitoring device were used to obtain the wearer’s walking dynamics, electromyography (EMG) signals, exoskeleton drive status and local human-computer interaction information. The human-machine coupling model was established in modeling environment of the bone system, and the gait experiment data and the exoskeleton joint torques were used as driving information of the coupling model to perform inverse mechanical calculations. Finally, by adjusting strength and stiffness parameters of the virtual muscles, the real data of the model was compared with the experimental test result, to quantitatively evaluate effectiveness of the human-machine coupling model of the lower extremity exoskeleton. Results The normal interaction force calculated by inverse dynamics of the coupled model and the activation of lower limb muscles had a good consistency in response curve trend compared with measurement results of the gait experiment, and the interaction force results had a high degree of correlation (r=0.931, P<0.01), the root mean square error was small, and the peak error of lower limb muscle activation was lower than 5%. Conclusions The human-machine coupling model proposed in this study can effectively calculate the interaction force between human and exoskeleton. The establishment of the coupling model provides a theoretical basis for verification and iteration of the exoskeleton structure optimization and control algorithm, as well as performance evaluation on mobility assistance effects of the exoskeleton.