Objective:To observe the effect of enriched rehabilitation training on cognitive function, plasma mir-146a-5p microRNA precursor levels and inflammatory factors in persons with post-stroke cognitive impairment (PSCI).Methods:Fifty-eight persons with PSCI were randomly divided into an observation group and a control group, each of 29. The observation group was given enriched rehabilitation training, while the control group was provided with conventional cognitive rehabilitation training. The Montreal Cognitive Assessment Scale (MoCA), the Digit Span Test (DST), parts A and B of the Trail Making Test (TMT A-B) and the Modified Barthel Index (MBI) were used to assess the subjects′ cognitive functioning and their ability in the activities of daily living (ADL). Plasma levels of mir-146a-5p, IL-6 and TNF-α were detected before and after the treatment.Results:After treatment, the average MOCA, DST and MBI scores, as well as the average TMT A-B times had improved significantly for both groups. However, the observation group′s averages were significantly better than those of the control group on all three tests. After the treatment, the average plasma expression of miR-146a-5p had increased significantly in both groups, but the increase in the observation group was significantly greater. Plasma IL-6 and TNF-α levels were significantly lower than before the treatment, with the average TNF-α level in the observation group significantly lower than that of the control group.Conclusions:Enriched rehabilitation training can improve the cognition of stroke survivors more effectively than conventional cognitive rehabilitation training. That may be related to the up-regulation of plasma miR-146a-5p and reducing inflammation.

Objective:To investigate the effect of arthroscopic superior capsular reconstruction (ASCR) of irreparable massive rotator cuff tears (RCTs) using the "Sandwich" patch graft (autologous fascia lata + LARS artificial ligament + autologous fascia lata).Methods:The patients with irreparable massive RCTs who underwent ASCR by using "Sandwich" patch graft were retrospectively evaluated between December 2016 and October 2018. All cases were followed up more than two years. The pain and function of the shoulder were evaluated by visual analogue scale (VAS), active forward elevation (aFE), American Shoulder & Elbow Surgeons score (ASES), University of California Los Angeles (UCLA) score, and Constant-Murley score. The acromiohumeral distance (AHD) and patch healing were assessed by shoulder X-ray and MRI scan.Results:Twenty-nine patients (12 males and 17 females) were enrolled for final analysis. The average age was 66.0±5.88 years (range 55-77 years). The average length of follow-up was 35.3±7.20 months (range 24-46 months). The tendon of the subscapularis muscle was intacted in 13 cases and repairable in 16 cases. All patients' teres minor muscles were intact and the function of deltoid muscles was all complete. Based on Hamada classification of massive RCTs, 11 cases with type 2, 14 cases with type 3, and 4 cases with type 4. At the last follow-up visit, the AFE of the surgical shoulder was 158.45°±23.87° (range 70°-180°), which was significantly higher than before the surgery 92.59°±45.99° (range 20°-160°, t=6.190, P<0.001). The ASES score was 92.92±9.08 (range 64-100), UCLA score was 31.62±3.93 (range 19-35), and Constant-Murley score was 85.8±8.44 (range 68-94), which were higher than those before the operation 30.69±12.99 (range 68-95), 10.93±3.43 (range 4-17), 39.62±12.68 (range 14-55). There were significant differences between them, respectively ( t=21.145, P<0.001; t=21.348, P<0.001; t=16.333, P<0.001). The VAS was 0.41±0.57 (range 0-2 points), which was significantly lower than that of 4.90±1.05 (range 3-7 points) before operation ( t=20.267, P<0.001). At the last follow-up visit, MRI showed that the AHD increased from 3.31±1.57 mm (range 1.1-6.6 mm) to 6.94±1.76 mm (range 3.0-10.8 mm) significantly ( t=12.195, P<0.001). Radiological outcomes were evaluated according to MRI, the total healing rate was 89.7% (26/29). There were two cases of complete tears, which including one case of infection and 1 partial tears. Conclusion:ASCR of irreparable massive RCTs using "Sandwich" patch graft showed the high healing rate in the short-term follow-up, which is possible to restore the shoulder functions early. It is an effective method for the treatment of irreparable massive RCTs.

BACKGROUND: Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cellbased administration. METHODS: In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. RESULTS: It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intraarticular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+ regenerative M2 macrophages over CD86+ M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. CONCLUSION Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.

Objective: To investigate the clinical outcomes of arthroscopic bridging reconstruction of irreparable massive rotator cuff tears using autogenous fascia lata. Methods: From July 2015 to July 2017, a total of 10 cases (4 male and 6 female) who were treated with arthroscopic bridging reconstruction for irreparable massive rotator cuff tears using autogenous fascia lata were retrospectively analyzed. The age before surgery was 61.3±2.9 years (range 57-67 years). There were 7 patients with right shoulders and 3 with left shoulders. The dominate sides were involved in 7 cases. The trauma history was documented in 2 shoulders. The duration of preoperative symptoms was 14.0±13.5 months (1-48 months). The case with revision surgery was not included. The patients were examined with magnetic resonance imaging (MRI) to evaluate the healing of fascia lata patch bridging in the joint at one week, six months, one year and two years after operation. The motion range of shoulder and the clinical scores, including visual analogue scale (VAS), University of California Los Angeles (UCLA) score, Constant-Murley score and American Shoulder & Elbow Surgeons (ASES) score, were measured before surgery and at follow-up duration. Results: All cases were reconstructed the horizontal couple. No perioperative complication was occurred and all surgery were completed safely and successfully. At the end of two years, the score of ASES was 92.2±3.5 (range 88.3-98.3), UCLA 31.6±2.0 (range 28-34), Constant-Murley 85.2±5.4 (range 78-93) with significant difference (t=11.254, P=0.000; t=12.111, P=0.000; t=8.948, P=0.00) comparing with that before surgery. The VAS pain score was 0.6±0.5 (range 0-1) which was significantly lower than that preoperatively (t=11.326, P=0.000). At 2 years after operation, MRI shows that fascia lata patches healed well in 9 patients. However, one case was with re-tear and patch absorption. The range of motion of shoulder was significantly improved in all patients but with different degrees of weakness (3-4). Conclusion Arthroscopic bridging reconstruction using autogenous fascia lata could effectively improve shoulder function in patients with irreparable massive rotator cuff tears. The autogenous fascia lata patch can heal with the help of rotator cuff tissue through bridging reconstruction.

Objective To explore the effect of task-oriented training of intelligent mirror gloves combined with low-frequency repeti-tive transcranial magnetic stimulation(rTMS)on hand function recovery in stroke patients. Methods From October 1st,2022 to June 30th,2023,136 stroke patients in Northern Jiangsu People's Hospital were ran-domly divided into control group,mirror group,rTMS group and combination group,with 34 patients in each group.All the groups received routine rehabilitation treatment.In addition,the mirror group received task-orient-ed training of intelligent mirror gloves,rTMS group received low-frequency rTMS,and the combination group received task-oriented training combined with low-frequency rTMS,for four weeks.The Fugl-Meyer Assess-ment-Upper Extremities(FMA-UE)score,Wolf Motor Function Test(WMFT)score,and surface electromyo-graphic root mean square(RMS)of forearm extensor and flexor muscle groups on the affected/healthy side be-fore and after treatment were compared.And the differences of transcranial magnetic stimulation-motor-evoked potentials(MEP)between rTMS group and combination group before and after treatment were also compared. Results Four cases in the control group,seven in the mirror group,five in rTMS group and six in the combination group dropped off.The intra-group effect(F>996.656,P<0.001),inter-group effect(F>20.333,P<0.001)and inter-action effect(F>72.796,P<0.001)were significant in the scores of FMA-UE and WMFT,and the RMS ratio of forearm extensor and flexor muscle groups among four groups,in which the combination group was the best.After treatment,the amplitude of MEP increased in rTMS group and combination group(|t|>3.842,P<0.05),and was higher in the combination group than in rTMS group(t=-3.060,P<0.01). Conclusion The task-oriented training of intelligent mirror gloves combined with low-frequency rTMS could effectively promote the recovery of hand function in stroke patients.

Objective:To observe any effect of combining motor imagery therapy (MIT) with repeated transcranial magnetic stimulation (rTMS) for improving upper limb motor functioning after a stroke.Methods:Ninety stroke survivors were randomly divided into a control group, an MIT group and a combination group, each of 30. All received conventional rehabilitation therapy, while the MIT group additionally received MIT and the combination group received the MIT along with 1Hz rTMS applied over the M1 region of the contralateral cortex. Before and after 4 weeks of treatment, everyone′s upper limb functioning was quantified using the Fugl-Meyer assessment scale (FMA) and the Hong Kong version of the hemiplegia upper limb function test (FTHUE-HK). Motor evoked potentials (MEPs), cortical latency (CL) and central motor conduction time (CMCT) were also recorded.Results:After the treatment the average FMA and FTHUE-HK scores of all three groups had improved significantly. The average CL and CMCT were significantly shortened. Compared with the control group, the average upper limb FMA score and FTHUE-HK scores of the treatment group were significantly higher. The combination group showed a significant improvement in its average MEP cortical latency and CMCT values.Conclusions:MIT therapy alone can improve the upper limb motor functioning of stroke survivors, but it is more effective in combination with rTMS.

Objective:To test the expression of miR-146a-5p RNA, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) as markers for predicting post-stroke cognitive impairment (PSCI).Methods:Forty cerebral infarction patients who had been followed up after 3 months formed a PSCI group, and another 40 who showed no post-stroke impairment formed the normal (PSCN) group. Forty healthy age-matched people were the AMC group. The executive functioning of each participant was quantified using the digital span test (DST), a Stroop color word test (SCWT), part B of the trail making test (TMT-B), and a semantic fluency test (SFT). Plasma expression levels of miR-146a-5p, IL-6 and TNF-α were also recorded. Receiver operating characteristics (ROC) curves were prepared to analyze the value of the miR-146a-5p, IL-6, TNF-α and Montreal cognitive assessment (MoCA) scores for predicting PSCI.Results:At baseline, the average expression of plasma miR-146a-5p in the PSCI group was significantly lower than in the other groups, with that of the PSCN group significantly higher than the AMC group′s average. Plasma IL-6 content in the PSCI group was significantly higher than in the other two groups on average, with that in the PSCN group significantly higher than in the AMC group. The average TNF-α levels in both the PSCI and PSCN groups were significantly higher than in the AMC group. Three months later, however, the average DST and SFT scores of the PSCI group were significantly lower than those of the other two groups, while TMT-B and stroop interference effects (SIE) times were significantly longer. TMT-B and SIE times in the PSCN group averaged significantly longer than in the AMC group. At baseline, the area under the curve predicting PSCI of plasma miR-146a-5P combined with MoCA scores was 0.90, with a sensitivity of 72.5% and specificity at the optimal critical point of 97.5%.Conclusions:A high level of plasma miR-146a-5p in the acute stage may protect an ACI patient′s cognitive functioning by inhibiting neuroinflammatory responses. Its expression level and the patient′s MoCA score can help to predict PSCI.

Objective To evaluate the regulatory effect of Diwu Yanggan(DWYG)Decoction on lysoglycerophospholipids(Lyso-GPLs)in circulating exosomes in a mouse model of nonalcoholic fatty liver disease(NAFLD).Methods Circulating exosomes isolated from mouse serum by size exclusion chromatography were morphologically characterized using transmission electron microscope and examined for surface markers CD9,CD63 and TSG101 using Western blotting.Twenty-four male Kunming mice were randomized into 3 groups for normal feeding(control,n=8)or high-fat diet feeding for 1 week to induce NAFLD,after which the latter mice were given DWYG decoction(treatment group,n=8)or normal saline(model group,n=8)by gavage for 4 weeks.After the last treatment,blood samples were collected from the mice for testing serum TC,HDL-C,LDL-C,ALT and AST levels and isolating circulating exosomes.Using multivariate statistical analysis based on targeted metabolomics strategy,the potential biomarkers for Lyso-GPLs in the exosomes were screened.Results The isolated exosomes about 100 nm in size had a typical saucer-like structure with distinct double-layer membranes and a mean particle size of 137.5 nm and expressed the specific surface marker proteins CD9,CD63 and TSG101.The mouse models of NAFLD had significantly increased serum levels of TC,HDL-C,LDL-C and AST and lowered serum ALT level.A total of 43 Lyso-GPLs with significant reduction after DWYG Decoction treatment were identified in NAFLD mice.Conclusion DWYG Decoction can regulate Lyso-GPLs in circulating exosomes in NAFLD mice,which provides a new clue for studying the therapeutic mechanism of DWYG Decoction for liver disease.

Objective To evaluate the regulatory effect of Diwu Yanggan(DWYG)Decoction on lysoglycerophospholipids(Lyso-GPLs)in circulating exosomes in a mouse model of nonalcoholic fatty liver disease(NAFLD).Methods Circulating exosomes isolated from mouse serum by size exclusion chromatography were morphologically characterized using transmission electron microscope and examined for surface markers CD9,CD63 and TSG101 using Western blotting.Twenty-four male Kunming mice were randomized into 3 groups for normal feeding(control,n=8)or high-fat diet feeding for 1 week to induce NAFLD,after which the latter mice were given DWYG decoction(treatment group,n=8)or normal saline(model group,n=8)by gavage for 4 weeks.After the last treatment,blood samples were collected from the mice for testing serum TC,HDL-C,LDL-C,ALT and AST levels and isolating circulating exosomes.Using multivariate statistical analysis based on targeted metabolomics strategy,the potential biomarkers for Lyso-GPLs in the exosomes were screened.Results The isolated exosomes about 100 nm in size had a typical saucer-like structure with distinct double-layer membranes and a mean particle size of 137.5 nm and expressed the specific surface marker proteins CD9,CD63 and TSG101.The mouse models of NAFLD had significantly increased serum levels of TC,HDL-C,LDL-C and AST and lowered serum ALT level.A total of 43 Lyso-GPLs with significant reduction after DWYG Decoction treatment were identified in NAFLD mice.Conclusion DWYG Decoction can regulate Lyso-GPLs in circulating exosomes in NAFLD mice,which provides a new clue for studying the therapeutic mechanism of DWYG Decoction for liver disease.