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.

Objective: : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods: : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results: : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

Objective: To identify the status and determinants of sharing personal HIV information with sexual partners among men who have sex with men (MSM) meeting their casual sexual partners on the internet. Methods: A cross-sectional study was conducted in five cities (Hangzhou, Ningbo, Wenzhou, Taizhou and Shaoxing) in Zhejiang province. The recruitment was enrolled by MSM social organization and in voluntary counseling and testing clinics, with a sample size of 793. A self-designed network questionnaire collected essential characteristics, HIV knowledge, sexual behavior, and sharing personal HIV status. SPSS 20.0 software was used for statistical analysis. Results: Among 767 MSM enrolled 302 MSM who reported finding casual sexual partners on the internet were enrolled in the analysis. MSM reported finding casual partners on the internet only, finding sexual partners online and in places were 62.6% (189/302) and 37.4% (113/302), respectively. Among those reporting web-based sexual behavior in the last six months, 54.6% (165/302) informed their partners of their HIV status, 49.2% (146/297) inquired about HIV status, and 42.9% (82/191) knew HIV status before sex intercourse, 75.8% (113/149) reported consistent condom use with HIV negative partners. The multivariable logistic regression analysis showed that related factors of inconsistent inquired HIV status of partners included 25-34 years old (aOR=2.17, 95%CI: 1.20-3.91), >2 partners on the internet in the last six months (aOR=2.13, 95%CI: 1.27-3.57), low-risk perception of HIV infection with online partners (aOR=1.96, 95%CI:1.14-3.35), numbers of HIV testing >1 times (aOR=0.38, 95%CI: 0.22-0.66). Conclusions: The willingness to know the HIV status of partners among MSM who met sexual partners on the internet was high but with a low rate of knowing their sex partner's HIV status in Zhejiang province. However, the successful implementation proportion was low. Therefore, it is necessary to pay attention to people who are elderly, with less conscience about the risk of the sex partners on the internet, have more sex partners, and have received few HIV tests. In addition, peer education was needed to promote related intervention programs.
Aged ; Male ; Humans ; Adult ; Sexual Partners ; Homosexuality, Male ; HIV Infections ; Cross-Sectional Studies ; Sexual and Gender Minorities ; Sexual Behavior ; Information Dissemination ; Internet

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

BACKGROUND: Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. METHODS: In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. RESULTS: The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein. CONCLUSION Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
Adaptor Proteins, Signal Transducing ; Adult ; Arteriosclerosis Obliterans/genetics* ; Autophagy ; GRB2 Adaptor Protein ; Humans ; Phosphoproteins/metabolism* ; Phosphorylation ; Protein Binding ; Signal Transduction

Purpose: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers—such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. Materials and Methods: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. Results: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)–negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. Conclusion These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

Objective To investigate the protective effect of sulodexide (SDX) on oxidized low density lipoprotein (ox-LDL) induced damage to human umbilical vein endothelial cell (HUVEC),and to discuss its mechanism.Methods By using CCK-8 method,the ox-LDL intervention HUVEC dose and the concentration of SDX were determined.The reactive oxygen species (ROS) assay kit was used to verify the protective effect of SDX on HUVEC.Real time fluorescent quantitation-polymerase chain reaction (RT-PCR) was employed to test the endothelial nitric oxide synthase (eNOS) and caveolin-1 mRNA expression;immunoblot assay was adopted to check the protein expression of phosphorylated eNOS (p-eNOS) and caveolin-1.The ability of cell migration was assessed by Transwell assay.Results Stimulated by 100 μg/ml concentration of ox-LDL,the cell viability of HUVEC decreased significantly (P＜0.01).After adding 125 LRU/ml concentration of LDX,the cell viability of HUVEC was remarkably improved (P＜0.01) and the production of ROS was strikingly decreased (P＜0.01).SDX could down-regulate the expression of caveolin-1 (P＜0.05) and up-regulate the expression of eNOS mRNA and p-eNOS (P＜0.05) for ox-LDL-damaged HUVEC,and markedly improve the migration ability of damaged HUVEC (P＜0.01).Conclusion By regulating the caveolin-1/eNOS signal route,SDX can improve impaired HUVEC cell migration ability,thus,to protect endothelial cells.

Objective To summarize clinical experience of one-station therapy for infected seriouslyischemic diabetic foot.Methods The clinical data of 15 patients (15 diseased limbs in total) with infected seriously-ischemic diabetic foot,who were admitted to authors' hospital during the period from June 2015 to April 2016 to receive treatment,were retrospectively analyzed.For all patients,one-station sequential therapy was carried out,which included endovascular revascularization (EVR) to open occluded vessel,surgical debridement and closed negative pressure wound drainage and antiseptic moisturizing wound dressing.The healing rate of infected wound and the limb salvage rate were evaluated.Results The 15 patients included 10 males and 5 females,with a median age of 77 years old.Lower extremity angiography showed that multiple segmental lesions of lower limb were detected in 13 patients and simple leg lesions in 2 patients.According to TASC Ⅱ update classification,leg artery disease of grade D was observed in 13 patients and artery disease of grade C in 2 patients.After EVR therapy,at least one branch of leg arteries was reopened in 14 limbs.Intact arterial arch of pedal-plantar loop (PPL) was seen in 6 patients,semi-arterial arch in 7 patients,and absent of arterial arch in 2 patients.After surgical debridement,the wound was washed by using negative pressure wound therapy (NPWT) device as well as serf-made washing equipment.The time to control wound infection was (7.85±2.84) days.After discharge,the patients were followed up every 3-4 days,at the same time wound dressing exchange with antibacterial moisturizing sulfadiazine silver lipid hydrogel was conducted.Wound healing was achieved in 12 patients,and the mean healing time was (3.70±0.87) months.The wound failed to heal in 3 patients,among them below knee amputation had to be performed in 2 patients (13.3％,both patients showed absent of arterial arch of PPL),and the remaining one patient died of cardiovascular event.Statistically significant difference in PPL pathological changes existed between wound healing group and wound un-healing group (P=0.006 7).Conclusion The treatment of infected seriouslyischemic diabetic foot is rather complicated.Being one-station therapy,the sequential managements,which include EVR,NPWT device together with washing equipment and use of antibacterial moisturizing wound dressing,can effectively increase the blood supply to the affected limb,shorten the time to control infection and lower amputation rate.Therefore,one-station therapy should be regarded as the preferred method for infected seriously-ischemic diabetic foot.

BACKGROUND:Compared with the cone stem,short stem holds good matching with femoral canal,and remarkably reduces the risk of prosthesis loosening.OBJECTIVE:To further investigate the clinical efficacy of Accolade Ⅱ stem for Crowe type Ⅰ developmental dysplasia of the hip.METHODS:Clinical data of 16 patients with Crowe type Ⅰ developmental dysplasia of the hip undergoing total hip arthroplasty using Accolade Ⅱ stem were collected,the length of both lower limbs before and after surgery was compared,and the Visual Analogue Scale,functional recovery of the hip and general conditions were observed at 12 weeks postoperatively.RESULTS AND CONCLUSION:(1) The change in length of both lower limbs before and after surgery had significant difference (P ＜ 0.05),and 10 patients (62％) with the same length of both lower limbs before surgery,and 15 cases (94％) after surgery.(2) The postoperative acetablar abducent angle was 41°-54° (average 46.9°).(3) The Visual Analogue Scale and Harris hip scores after surgery were significantly improved compared with baseline (P ＜ 0.05).(4) The intraoperative blood loss was 147 mL on average,the mean operation time was 72 minutes,and the hospitalization time was 7.2 days.(5) All patients recovered well and no complications occurred at 3 months postoperatively.(6) To conclude,Accolade Ⅱ stem is safe and reliable for Crowe type Ⅰ developmental dysplasia of the hip,and exhibits good functional recovery of the hip.

Objective To observe the clinical efficacy and safety of different doses of atorvastatin calcium tablets in the treatment of ischemic anterior stroke with middle cerebral artery occlusion (MCA).Methods A total of 146 patients of ischemic anterior stroke with MCA were randomly divided into control group and treatment group with 73 cases per group.Control group was treated with atorvastatin calcium 10 mg,qd,oral.Treatment group was treated with atorvastatin calcium 40 mg,qd,oral.Two groups were treated for 1 year.The clinical efficacy,the National Health Surveys Stroke Scale (NHISS) score,the daily living ability scale-Barthel index (ADL-BI) score,and adverse drug reactions were compared between two groups.Results After treatment,the total effective rates of treatment and control groups were 90.41％ (66/73 cases) and 76.71％ (56/73 cases) with statistically significant difference (P ＜ 0.05).After treatment,the NHISS scores of treatment and control groups were (8.24 ± 1.65),(12.03 ±2.21) points;the ADL-BI scores of treatment and control groups were (80.94 ± 2.67),(68.75 ±3.83) points,the differences were statistically significant (all P ＜0.01).The adverse drug reactions in the treatment group were based on gastrointestinal discomfort,transient transaminase and creatine kinase levels increased,which in the control group were gastrointestinal discomfort.The incidences of adverse drug reactions in treatment and control groups were 8.22％ and 1.37％ without significant difference (P ＞ 0.05).Conclusion Atorvastatin calcium tablets 40 mg has a definitive clinical efficacy in the treatment of ischemic anterior stroke with MCA,without increasing the incidence of adverse drug reactions.