BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Currently, the management of domestic laboratory developed test (LDT) is still in the exploration stage, and new plans and ideas need to be investigated that are suitable for our national development. By analyzing encountered issues, combining the actual needs of the government, healthcare reform, and patients, this article proposes that "promoting healthy development of LDT projects and focusing on the organic combination of patients′ interest protection and innovation support" is an important direction for LDT management, around which the new idea for LDT project management is proposed, that is, LDT management model targeting product registration. The core of this management model is to target product registration and to ensure low service fees for patients and continuous real-time data monitoring. Benefit and risk analysis demonstrate that this management model can to a larger extent balance the realistic demands of patients, medical institutions, in vitro diagnostics companies, and government management departments, which benefits promoting the perfection and development of LDT projects in our country.

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes (T2DM). Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge. Neutral sphingophospholipase 2 (Smpd3) is downregulated in jawbone-derived bone marrow mesenchymal stem cells (BMSCs) from T2DM patients. Here, we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles. The combined loading of Smpd3-overexpressing stem cell-derived exosomes (Exos-Smpd3) and nanosilver ions (Ns) to construct a hydrogel delivery system (Exos-Smpd3@Ns) promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment, ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro. Mechanistically, Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations. These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations, providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.
Exosomes ; Animals ; Bone Regeneration/drug effects* ; Dogs ; Mesenchymal Stem Cells ; Humans ; Blood Glucose ; Cell Differentiation ; Osteogenesis/drug effects* ; Diabetes Mellitus, Type 2/therapy* ; Diabetes Mellitus, Experimental ; Cells, Cultured ; Hydrogels ; Male

Objective:To study the expression characteristics of myocardial strain index after the abnormal origin of the left coronary artery of the pulmonary artery in children was repaired.Methods:The data of 30 children (study group) with abnormal origin of pulmonary artery left coronary artery repair from August 2017 to August 2021 were analyzed. In addition, healthy children during the same period were selected as the control group, and the study group was compared before and after treatment and the control group. Circumferential and radial peak myocardial strain index, post-contraction strain index.Results:The longitudinal, circumferential, and radial overall peak strain indexes of the study group before and after treatment were significantly lower than those of the control group, and the longitudinal, circumferential, and radial overall peak strain indexes of the study group after treatment were significantly higher than those before treatment ( P<0.05); The longitudinal, circumferential, and radial peak strain indexes of the study group before treatment were significantly lower than those of the control group. After treatment in the study group, the middle section of the longitudinal inferior wall, the middle section of the anterior wall, the basal section of the anterior wall, the apex, and the circumferential direction were significantly lower The peak strain index of the basal segment of the inferior wall and the middle segment of the inferior wall was significantly lower than that of the control group; and the longitudinal, circumferential, and radial peak strain indexes of the study group after treatment were significantly higher than those before treatment ( P<0.05); the study group children before treatment Longitudinal, circumferential, and radial PSI indexes were significantly lower than those of the control group. After treatment, the study group was treated in the longitudinal inferior wall, septal apical segment, circumferential inferior wall basal segment, inferior wall middle segment, and radial PSI anterior wall basal segment, apex. The part was significantly higher than that of the control group; and the longitudinal, circumferential, and radial PSI of the study group after treatment were significantly lower than before treatment ( P<0.05). Conclusion:After ALCAPA repair, the overall and regional strain and overall synchronization are improved, indicating that the resting myocardium has recovered, but the strain of certain segments supplied by the abnormal left coronary artery fails to normalize after ALCAPA repair. Persistent myocardial injury is consistent, which can provide some guidance for the prognosis assessment of children with ALCAPA.

【Objective】 To investigate the effects of one-stage additional posterior pedicle screws （PPS） internal fixation on early Cage subsidence after oblique lateral interbody fusion （OLIF）. 【Methods】 We made a retrospective analysis of 118 patients with lumbar degenerative diseases treated with OLIF at the Department of Orthopedics， Sir Run Run Shaw Hospital， School of Medicine， Zhejiang University， from January 2016 to December 2019. We divided the patients into OLIF stand-alone group （58 ones） and OLIF with PPS fixation group （60 ones） according to the surgical procedure. All the patients had preoperative frontal and lateral radiographs of the lumbar spine， and CT and MR scans were performed. The clinical outcomes and reoperation rates of the two groups were compared at immediate postoperative follow-up and at 1， 3， 6 and 12 months. X-ray and CT examinations were performed to assess Cage subsidence in both groups at each postoperative follow-up. 【Results】 There was no statistical difference between the two groups in baseline data and surgical segmentation. Of the 118 patients with 141 discs who underwent OLIF surgery， 58 patients with 68 discs received OLIF stand-alone surgery and 60 ones with 73 discs received OLIF with PPS fixation. There were no significant differences in intraoperative bleeding， complications， or postoperative clinical outcomes between the two groups （P>0.05）， and the Cage subsidence rate was 22.4% in OLIF stand-alone group and 5% in OLIF with PPS fixation group， with significant difference between the two groups （P<0.01）. 【Conclusion】 Both OLIF stand-alone and OLIF additional PPS fixation can achieve good early clinical outcomes， and first-stage additional PPS fixation can significantly reduce the occurrence of Cage subsidence in the early postoperative period after OLIF.

Due to the extensive use of xylooligosaccharides (XOS) as functional food ingredients,many inferior goods and even adulterants are generally found in the market,which may pose a health hazard to certain populations.Chromatography method such as high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC) is traditionally applied for the quality analysis of XOS.However,it is time consuming due to the prolonged separation and pre-or post-derivatization procedure.In this study,a fast saccharide mapping method based on matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF-MS) was developed for the quality consistency analysis of 22 batches of XOS collected from different manufacturers in China.The time needed for saccharides analysis using MALDI-MS was less than 30 min for one plate,at least 6 times faster than that by the traditional HPTLC chromatography method.In addition,MALDI-MS possessed higher resolution for XOS with DP4-DP7 based on the difference of m/z,which is hardly separated using HPTLC.The results showed that XOS were present only in samples XY01-XY11,samples XY12-XY14 only consisted of hex oligo-saccharides,and samples XY15-XY22 were free of oligosaccharides.These indicate that the quality consistency of XOS products in the China market was poor,which should be carefully investigated.

Objective:To investigate the risk factors of muscle necrosis in patients with acute compartment syndrome（ACS）.Methods:A retrospective case-control study was conducted for clinical data of 111 ACS patients admitted to West China Hospital, Sichuan University from January 2010 to December 2020, including 84 males and 27 females; age 18-76 years [45（36, 55）years]. Muscle necrosis was presented in 35 patients（necrotic muscle group）, but was not seen in 76 patients（non-necrotic muscle group）. The univariate analysis was performed for the two groups in the demographic data（sex, age, ethnicity, body mass index, smoking history, chronic comorbidities）, injury patterns [ mechianism of injury（low energy injury, high energy injury, crush injury, other injury）, time from injury to treatment, first visit or not, combination with bone fracture or not, open injury or not, presence of tension blisters or not], medical treatment（number of debridements, fasciotomy or not）and laboratory indicators [hemoglobin（Hb）, platelet count（PLT）, white blood cell count（WBC）, prothrombin time（PT）, international normalized ratio（INR）, partially activated prothrombin time（APTT）, fibrinogen（FIB）, D-Dimer（D-D）, alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, albumin（ALB）, intravenous blood glucose（GLU）, creatine kinase（CK）, peak value of CK during hospitalization（natural logarithmic conversion, lnCK）, serum sodium（NA）, serum potassium（K）, serum calcium（CA）]. Further multivariate logistic regression was performed to analyze the independent risk factors of muscle necrosis in ACS patients.Results:The univariate analysis showed that there were statistically significant differences between the two groups in the mechanism of injury, first visit or not, combination with bone fracture or not, number of debridements, Hb, PT, INR, D-D, AST, ALB, GLU, CK and lnCK（ P<0.05）, while not in the basic data, time from injury to treatment, open injury or not, presence of tension blisters or not, fasciotomy or not, PLT, WBC, APTT, FIB, ALT, NA, K and CA（ P>0.05）. The multivariate logistic regression analysis showed that high energy injury（ OR=5.143, 95% CI 1.216-21.758, P<0.05）, crush injury（ OR=22.313, 95% CI 2.625-189.635, P<0.05）, other mechanism of injury（ OR=9.019, 95% CI 1.036-78.554, P<0.05）, first visit or not（ OR=0.071, 95% CI 0.006-0.819, P<0.05）, Hb（ OR=0.979, 95% CI 0.961-0.998, P<0.05）, GLU（ OR=1.218, 95% CI 1.020-1.455, P<0.05）and lnCK（ OR=1.805, 95% CI 1.235-2.639, P<0.05）were significantly related with muscle necrosis. Conclusion:The mechanism of injury, first visit or not, Hb, GLU and lnCK are the independent risk factors of muscle necrosis in patients with ACS.

Objective:The purpose of this study is to analyze the surveillance data of the Integrated HCV surveillance in Shanghai and provide a scientific basis for HCV's elimination strategies.Methods:Descriptive statistical analysis and multivariate logistic regression analysis were performed using the multi-dimension results of the Integrated HCV surveillance in Shanghai from 2014 to 2019. Data related to reported HCV cases, HCV gene subtypes surveillance, HCV behavioral risk factors surveillance and HCV-antibody testing results of the community-based general population and high-risk/key populations.Results:The reported incidence rate of acute hepatitis C in Shanghai decreased from 2014 to 2019 ( Z=-4.07, P<0.01); meanwhile, the reported incidence rate of chronic hepatitis C met an upward trend ( Z=10.26, P<0.01), with an annual average, reported incidence rates of 0.18 per 100 000 and 8.60 per 100 000, respectively. Seven hundred forty-four blood samples were subtyped with 16 subtypes from 4 genotypes (GT1, GT2, GT3, and GT6). Among above, 1b (324 cases, 43.55%), 3a (121 cases, 16.26%), 3b (111 cases, 14.92%) and 6a (47 cases, 6.32%) were the principal subtypes. The composition of genotypes varied with decreased 1b and increased 3b and 6a. The major risk factors for HCV infection were blood transfusion ( OR=4.18, 95% CI: 2.79-6.27), surgery ( OR=1.63, 95% CI: 1.26-2.12), sharing syringe ( OR=4.18, 95% CI: 2.75-6.34), pedicure ( OR=2.01, 95% CI: 1.54-2.62), sharing razors ( OR=4.09, 95% CI:1.24-13.51), and unsafe beauty practices ( OR=3.15, 95% CI: 2.13-4.65). HCV antibody screening of 11 groups of high-risk/key populations showed that drug users had the highest HCV-antibody positive rate of 18.81% (1 008/5 358). The anti-HCV positive rate of the general population was 0.16% (7/4 268), which was significantly lower than that of high-risk/key populations from the same year, 2.50%(501/20 002) ( χ2=94.04, P<0.01). Conclusions:Shanghai is a low-endemic area of HCV. Constantly carrying out integrated surveillance and analysis is of great value for early identification of HCV infected people and its risk factors, timely adjustment of prevention and control strategies, and eliminating the public health threat of HCV.

Objective:To explore the safety and efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory acute B-cell lymphoblastic leukemia (B-ALL) with T315I mutation.Methods:The clinical data of a patient with relapsed/refractory B-ALL with T315I mutation who underwent CAR-T therapy in the Second Affiliated Hospital of Anhui Medical University was analyzed, and the related literature was reviewed.Results:The patient was a 34-year-old man. He was diagnosed with chronic myelogenous leukemia (CML) in January 2017 and started to take imatinib orally. However, the primary affection transformed to B-ALL 4 months later. Because of the E355G gene mutation, the treatment drug was adjusted to dasatinib, and induction chemotherapy was given at the same time. The sequential consolidation chemotherapy was given for 3 times after complete remission (CR). After half a year of remission, T315I mutation was detected and re-induced chemotherapy was given, but ineffective. The patient was treated with CAR-T 3 days after FC regimen (fludarabine 30 mg/m 2 per day, day 1 to day 3; cyclophosphamide 200 mg/m 2, day 1 to day 3). The number of CD19 CAR-T was 1.0×10 9, 98% activity degree. Grade 1 cytokine-releasing syndrome appeared after infusion, and was resolved after symptomatic treatment. No serious adverse reactions were observed. CR was achieved half-month after CAR-T treatment, and umbilical cord blood transplantation was successfully performed 1 month later. At the last follow-up, the relapse-free survival time of the patient was 396 days. Conclusion:CAR-T therapy may be a new, safe and effective therapy for patients with relapsed/refractory B-ALL with T315I mutation.