BACKGROUND:Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis. OBJECTIVE:To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair. METHODS:Databases such as CNKI and PubMed were searched.The English key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,electrostatic interaction,covalent crosslinking",and the Chinese key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,physical encapsulation,electrostatic effect,covalent cross-linking".After an initial screening of all articles based on inclusion and exclusion criteria,71 articles with high correlation were retained for review. RESULTS AND CONCLUSION:In cell or animal experiments,nanocomposite hydrogel has the effect of improving osteoarthritis.Nanocomposite hydrogel can promote cartilage repair,improve the internal environment of osteoarthritis,and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints,carrying targeted drugs,and promoting the chondrogenesis of seed cells.At present,the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play.It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments.

Objective We aimed to study the protective effect of total glucosides of paeony (TGP) on chemical liver injury with pattern of liver yin deficiency in rats and determine whether it exerts these effects through the phosphoinositide 3-kinase(PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.Methods Forty male Sprague-Dawley rats were randomly divided into the following four groups: (i) the blank group, (ii) the model group, (iii) the Yiguan Jian group, and (iv) the TGP group (10 rats per group). For 6 weeks, rats in all groups except for the blank group were injected intraperitoneally with 20％ carbon tetrachloride olive oil solution and were given thyroid tablets (30mg/kg) by gavage in order to establish the model of chemical liver injury with pattern of liver yin deficiency. During the modeling period, rats in the blank and model groups were gavaged daily with distilled water, while rats in the Yiguan Jian group and the TGP group were gavaged with 635mg/kg of Yiguan Jian decoction and 50mg/kg of TGP suspension, respectively. During the administration period, the body weight and rectal temperature of rats were measured every 2 weeks. After the administration, 24-hour food intake, 24-hour water intake, and moisture capacity in tongue surface were recorded. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1Ra) contents were measured by ELISA and the cAMP/cGMP ratio was calculated. Changes in the serum levels of alanine aminotransferase (ALT), alanine transaminase (AST), gamma-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), total bilirubin (TBIL), and total bile acids (TBA) were detected using colorimetric method. Masson staining was performed to observe the degree of liver fibrosis and to calculate the relative collagen area. Real-time PCR and Western blotting were conducted to determine the PI3K, AKT, and mTOR mRNA and protein expression levels in rat liver.Results Compared with the blank group, rats in the model group had a lower body weight at weeks 2, 4, and 6, a higher rectal temperature at weeks 2, 4, and 6, and a higher 24-hour food intake; the cAMP level was elevated, the cGMP level was decreased, and the cAMP/cGMP ratio was elevated; the contents of IL-1, IL-6, and TNF-α were elevated, and the contents of IL-10 and IL-1Ra were decreased; ALT, AST, γ-GT, ALP, TBIL, and TBA levels were elevated; the percentage of collagen area in the liver was increased; and the mRNA and protein phosphorylation levels of PI3K, AKT, and mTOR were elevated ( P<0.05). Compared with the model group, rats in the TGP group showed a decrease in rectal temperature at weeks 2, 4, and 6, a decrease in 24-hour food intake and water intake, and an increase in the moisture capacity in tongue surface; rats in the Yiguan Jian and TGP groups showed a decrease in cAMP, an increase in cGMP, and a decrease in the cAMP/cGMP, the contents of IL-1, IL-6, and TNF-α were decreased and the content of IL-10 was increased, the percentage of collagen area in the liver was decreased; ALT, AST, γ-GT, ALP, and TBIL levels were decreased in the TGP group, and PI3K, AKT, and mTOR were downregulated at the mRNA and protein levels(P<0.05).Conclusion TGP has a good protective effect on chemical liver injury with pattern of liver yin deficiency in rats. TGP may regulate the balance of yin and yang by inhibiting the PI3K/AKT/mTOR pathway, reducing the secretion of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines.

Objective We aimed to investigate(i)the preventive and therapeutic effects of Huogu Muli Prescription(HGMLP),a Chinese medical compound consisting of epimedii folium,drynariae rhizoma,and ostreae concha,on postmenopausal osteoporosis(PMOP)rats and(ii)whether it exerts its effects by regulating the osteoclast-osteogenesis balance.Methods Forty-eight female Sprague-Dawley rats were randomly divided into the following six groups:(i)the sham-operated group,(ii)the model group,(iii)the Qianggu Capsule group,(iv)the calcium carbonate group,and(v,vi)the HGMLP low-dose and high-dose groups(n = 8 rats per group).After adaptive feeding,rats in all groups except the sham-operated group were treated with bilateral ovarian castration to establish the PMOP model.Each day,rats in the Qianggu Capsule group received 0.054 g/kg Qianggu Capsule suspension intragastrically,rats in the calcium carbonate group received 1.670 g/kg calcium carbonate suspension intragastrically,and rats in the HGMLP low-dose and high-dose groups received 0.188 g/kg and 0.375 g/kg HGMLP intragastrically.Rats in the sham-operated group and the model group received an equal volume of normal saline intragastrically.After 90 consecutive days,serum estradiol(E2),estrogen receptor α(ERα),procollagen typeⅠN propeptide(PINP),and tartrate-resistant acid phosphatase 5b(TRACP-5b)were detected by ELISA.Total antioxidant capacity(T-AOC),superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels were measured by colorimetry.Bone mineral density(BMD),trabecular number(Tb.N),trabecular separation/spacing(Tb.Sp),trabecular thickness(Tb.Th),and structure model index(SMI)were measured by Micro-CT,and the microstructure of cancellous bone was observed.The expressions of osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK),RANK ligand(RANKL),phosphorylation of forkhead box O3(FoxO3α),Wnt2,β-catenin,and peroxisome proliferator-activated receptor γ(PPARγ)in rat femur tissue were detected by Western blotting.Results(i)The serum levels of E2 and ERα increased in the Qianggu Capsule group and HGMLP groups,compared with the model group(all P<0.05).(ii)Compared with the model group,the serum levels of PINP,TRACP-5b decreased and PINP/TRACP-5b increased in both the Qianggu Capsule group and HGMLP high-dose group(all P<0.05).(iii)The activities of T-AOC,AOD,and CAT in the Qianggu Capsule group and HGMLP groups were higher than those in the model group,while the content of MDA lower(all P<0.05).(iv)Compared with the model group,the femoral BMD,Tb.Th,and Tb.N increased in the Qianggu Capsule group and HGMLP groups,while the femoral Tb.Sp and SMI decreased(all P<0.05);the femoral BMD increased and the Tb.Sp decreased in the calcium carbonate group(all P<0.05).(v)The protein expressions of RANKL,RANK,FoxO3α,and PPARγ in the Qianggu Capsule group and HGMLP groups were lower than those in the model group,while the protein expressions of OPG,Wnt2,and β-catenin were higher(all P<0.05).Conclusion HGMLP can significantly increase estrogen levels,inhibit osteoclast differentiation,and inhibit bone resorption in the PMOP rats.It also alleviates oxidative stress,promotes osteogenic differentiation,inhibits lipogenic differentiation,improves bone formation,and recovers the balance between osteoclasts and osteoblasts,thus achieving prevention and treatment of PMOP.The potential mechanism of HGMLP may be related to regulation via the OPG/RANKL/RANK or FoxO3α/Wnt2/β-catenin/PPARγ pathways.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.

Objective To investigate the difference of electrocardiographic(ECG)features between total left main artery(LM)occlusion and subtotal occlusion,and analyze risk factors of in-hospital mortality.Methods A total of 94 patients with left main complete occlusion and 99 patients with subtotal occlusion were included.ECG characteristics,coronary angiography and other clinical data were compared,and factors of hospital death were analyzed.The receiver operating characteristics(ROC)curve was used to analyze the predictive value of ECG characteristics in hospital death risk in patients with LM occlusion.The relationship between ECG characteristics,shock and collateral circulation were analyzed in patients with LM occlusion.Results Compared with the subtotal occlusion group,patients with LM occlusion presented with more ST-segment elevation(STE)in Ⅰ,avL,V2-V5,more STE in avR and avL,more left anterior fascicular block+right bundle branch block,prolonged QRS duration,less STE in avR and less STE in avR+V1.The in-hospital mortality was 46.8%(44/94)in LM occlusion and 14.1%(14/99)in LM subtotal occlusion.STE in avR+avL predicted total LM occlusion with a specificity of 0.97,and left anterior branch+right bundle branch block predicted total LM occlusion with a specificity of 1.00.In patients with total LM occlusion,STE in Ⅰ,avL,V2-V5,prolongation of QRS duration,shock,no collateral circulation,STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block,and STE in Ⅰ,avL,V2-V5 combined with shock predicted in-hospital mortality,with the area under the curve of 0.716,0.619,0.766,0.688,0.572,0.785,respectively.The diagnostic specificity of STE in Ⅰ,avL,V2-V5 combined with shock was 0.82,and the sensitivity was 0.75.STE in Ⅰ,avL,V2-V5 combined with left anterior fascicular block+right bundle branch block predicted in-hospital death in LM occlusion with a specificity of 0.94.The proportion of shock was higher in patients with STE in Ⅰ,avL,V2-V5,left anterior fascicular block+right bundle branch block and collateral flow absence(P＜0.05).In patients with total occlusion,no collateral flow was observed in patients with STE in Ⅰ,avL,V2-V5.In patients with STE in avR(including avR+V1),82.4%of patients presented with right coronary collateral circulation supplying the left anterior descending coronary artery and left circumflex artery territory.In patients with STE in avR+avL,69.2%of patients presented with right coronary collateral circulation supplying left anterior descending coronary artery territory.Conclusion Total LM occlusion presents with different ECG features compared with subtotal occlusion.In LM total occlusion,the ECG features predict in-hospital mortality and are associated with different collateral circulation.

【Objective】 To explore the factors affecting Babinski sign in amyotrophic lateral sclerosis (ALS). 【Methods】 We enrolled 262 patients diagnosed with ALS with adequate data in Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University from 2015 to 2020. The relationship between the clinical characteristics of patients with positive and negative Babinski sign was analyzed for both sides, respectively. Furthermore, for patients with left or right lower limb weakness complaint, the relationship between Babinski sign and the lower limb involvement characteristics was analyzed. 【Results】 Positive Babinski sign was positively correlated with higher diagnostic category (left correlation coefficient 0.297, P<0.001; right correlation coefficient 0.292, P<0.001). Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was lower in patients with positive Babinski sign (left P=0.001, right P=0.001); the proportion of complaints of ipsilateral lower limb weakness was higher (left P=0.008, right P=0.038); the positive rate of ipsilateral upper limb Hoffmann sign was higher (left P=0.004, right P=0.002). In patients with complaints of lower limb weakness, positive Babinski sign was positively correlated with better foot dorsiflexor muscle strength (left correlation coefficient 0.207, P=0.021; right correlation coefficient 0.264, P=0.003), and the proportion of ipsilateral tibialis anterior atrophy was lower in positive Babinski sign group (left P<0.001, right P=0.008); the ratio of ipsilateral common peroneal nerve compound muscle action potential (CMAP)/tibial nerve CMAP was different in positive Babinski sign and negative groups (left P=0.008, right P=0.015), which were positively correlated (left correlation coefficient 0.246, P=0.007; right correlation coefficient 0.223, P=0.015). 【Conclusion】 Patients with positive Babinski sign usually have a higher diagnostic category and more extensive clinical involvement. In ALS patients with complaints of lower limb weakness, Babinski sign is more likely to be elicited when the degree of weakness and atrophy of the anterior calf muscles is relatively low.

【Objective】 To explore the characteristics of white matter degeneration in amyotrophic lateral sclerosis (ALS) patients with different onset and spreading patterns by using diffusion tensor imaging (DTI). 【Methods】 We enrolled 86 ALS patients and 44 healthy controls. The patients were divided into bulbar- and spinal-onset subgroups according to their onset site, as well as horizon, vertical, interpose/skip, and caudal-rostral subgroups based on the spreading direction of the involved regions. The white matter fiber tracts corresponding to the motor network were set as the region of interest. We used tract-based spatial statistics to evaluate differences between the above groups and the normal controls, with family-wise error (FWE) correction and P<0.05 as statistical significance. 【Results】 The white matter degeneration of ALS patients with bulbar onset was mainly limited to the corona radiation part of the corticospinal tract, while those with spinal onset showed extensive degeneration of corticospinal tract and corpus callosum Ⅲ area (FWE correction, P<0.05). In patients with horizontal and vertical dissemination, decreased integrity of the entire corticospinal tract was found, with patients in the latter group showed extra degeneration in the Ⅲ part of the corpus callosum. Restricted degeneration of the corticospinal tract within bilateral corona radiata was detected in patients with caudal-rostral and interposed/skip spreading pattens (FWE correction, P<0.05). 【Conclusion】 Different onset and disease spread patterns of ALS patients correspond to divergent brain degeneration patterns. The diagnosis, treatment, and management of ALS should fully consider the heterogeneity of the disease.

【Objective】 To investigate cortical thickness changes in the face-head region of the primary motor cortex (PMC) and its effect on survival in amyotrophy lateral sclerosis (ALS) patients. 【Methods】 A retrospective analysis was performed on 105 ALS patients who underwent head MRI scan at the same time. The A4hf (face-head) region of PMC was used as the region of interest (ROI). According to clinical symptoms, patients were divided into two groups: bulbar involvement and non-bulbar involvement. The differences of clinical features and cortical thickness in ROI were analyzed. According to the symptoms of bulbar palsy, physical examination of nervous system and EMG of tongue muscle, the patients with bulbar palsy were divided into lower motor neuron (LMN), upper motor neuron (UMN) and LMN+UMN groups. The differences of bulbar subgroup score and ROI of cortical thickness were analyzed. Age at onset, body mass index, delayed time of diagnosis, bulbar subgroup score, and ROI cortical thickness were included in survival analysis. 【Results】 ① The ROI cortical thickness was significantly lower in bulbar involvement group than non-bulbar involvement group (-0.198±0.87 vs. 0.235±0.95, P=0.017). ② There were no significant differences in the bulbar subgroup scores or cortical thickness of ROI between LMN, UMN and LMN+UMN groups (P>0.05). ③ Survival analysis showed age of onset (HR=3.296, 95% CI:1.63-6.664, P=0.001), delayed time of diagnosis (HR=0.361, 95% CI:0.184-0.705, P=0.003), bulbar subgroup score (HR 0.389, 95% CI:0.174-0.868, P=0.021), and ZRE_ROI cortical thickness (HR=2.309, 95% CI:1.046-5.096, P=0.038) were independent influencing factors of ALS survival. 【Conclusion】 Cortical thickness in A4hf (face-head) region can more objectively reflect UMN signs of region bulbar. In addition to age of onset and delayed time of diagnosis, bulbar subgroup score and cortical thickness of face-head region are also independent influencing factors, and cortical thinning in face-head region is a protective factor for survival of ALS patients.

【Objective】 To investigate changes in thalamus structure and function and their associations with cognitive impairment in patients with amyotrophic lateral sclerosis (ALS). 【Methods】 3D high-resolution structural imaging and resting-state fMRI were applied in 78 ALS patients and 49 healthy volunteers. The shape of the thalamus was assessed using a vortex analysis and functional connectivity between the thalamus subregion and cortex was evaluated by a seed-based correlation analysis. Partial correlation analysis was used to evaluate the correlation between focal thalamus alterations and clinical assessments. 【Results】 Compared with the control group, vertex analysis showed significant atrophy in the prefrontal and temporal subregions of bilateral thalamus in the ALS group. Patients exhibited increased functional connectivity of motor-sensory ROI with the right motor cortex, of temporal ROI with the bilateral lateral occipital cortex, precuneus and right temporal subregion. In contrast, decreased function connectivity was found mainly between temporal ROI and paracingulate gyrus, left dorsomedial prefrontal lobe and left caudate. Partial correlation analysis showed that the functional connectivity of the precuneus, paracingulate cortex, left caudate nucleus and left prefrontal lobe was correlated with multiple cognitive performances. 【Conclusion】 Selective damage of thalamic structure and function in ALS plays an important role in cognitive and behavioral disorders.

【Objective】 The involvement of upper motor neuron (UMN) degeneration is crucial to the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to determine objective and sensitive UMN degeneration markers for an accurate and early diagnosis. 【Methods】 A total of 108 ALS patients and 90 age- and gender-matched control subjects were recruited from ALS Clinic of The First Affiliated Hospital of Xi’an Jiaotong University. The motor homunculus cortex thickness data in MRI were collected from all the participants. The clinical characteristics and UMN clinical examination of bulbar, cervical, thoracic and lumbosacral regions were collected from the ALS patients. 【Results】 Cortical thickness was significantly thinner in the ALS group than in the control group in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the global UMN positive group was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the UMN positive group in the corresponding region was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). 【Conclusion】 The thinning of the motor homunculus cortex can be used as an objective marker of UMN involvement in ALS patients in clinical practice.