Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

OBJECTIVE: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type ⅢA and ⅢB open tibial fractures. METHODS: A retrospective study was performed on 22 patients with Gustilo type ⅢA and ⅢB open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type ⅢA fractures and 13 were type ⅢB fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. RESULTS: The wound area was 21.0-180.0 cm ² (mean, 57.82 cm ²) before operation, and it was 1.2-27.0 cm ² (mean, 6.57 cm ²) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). CONCLUSION Nice knot technique can be used in wound closure of Gustilo type ⅢA and ⅢB open tibial fractures effectively, which is easy to operate.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Cicatrix ; Retrospective Studies ; Treatment Outcome ; Tibial Fractures/surgery* ; Wound Healing ; Fracture Fixation, Internal/methods* ; Fractures, Open/surgery*

Objective To conduct a detailed clinical phenotypic analysis and gene mutation detection on an au-tosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examina-tion and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation expe-riencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.

Objective:To investigate the effects of transepithelial photorefractive keratectomy (TransPRK) and femtosecond small incision lenticule extraction (SMILE) on corneal biomechanics measured by the Ocular Response Analyzer in the early postoperative period.Methods:A cohort study was conducted.The right eyes of 56 patients who underwent TransPRK and 52 patients who underwent SMILE in Dalian Medical University Affiliated Dalian Third People's Hospital from November 2020 to June 2021 were continuously included.The postoperative follow-up was 3 months.The central corneal thickness (CCT) and keratometry (Km) were measured 1 month and 3 months after surgery.The corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF), corneal hysteresis (CH), and 19 repeatable mechanical infrared signal waveform parameters measured by the Ocular Response Analyzer were recorded before the surgery, 1 month and 3 months after the surgery, respectively.The measurement indexs at different time points between two groups were compared.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Dalian Medical University Affiliated Dalian Third People's Hospital (No.2019-KT-010). Written informed consent was obtained from each patient before surgery.Results:There was no significant difference in CCT, Km, and IOPcc between the two groups at 1 month and 3 months after the surgery (all at P>0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1, dive2 and mslew1 were decreased, while path1, path2, path11, and aplhf were increased at 1 month after the surgery compared with before surgery, showing statistically significant differences (all at P<0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1 decreased, while path1, path2, path11, and aplhf were increased at 3 months after the surgery in comparison with before surgery, showing statistically significant differences (all at P<0.05). In SMILE group, the dive2 were decreased at 3 months after the surgery compared with before surgery, and the difference was statistically significant ( P<0.01). At 1 month after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, dive1 and dive2 were higher, while CH, path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). At 3 months after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h2, h21, dive1 and dive2 were higher, while path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). Conclusions:Corneal biomechanics are weakened after both TransPRK and SMILE.In the early postoperative period, the mechanical infrared waveform parameters measured by the Ocular Response Analyzer are better after TransPRK than after SMILE.

Objective:To investigate the differences and changes in early postoperative visual quality after small incision lenticule extraction (SMILE) and smart pulse technology-assisted transepithelial photorefractive keratectomy (SPT-TransPRK).Methods:A cohort study was performed.A total of 92 patients (92 eyes) who underwent corneal laser refractive surgery were enrolled in Dalian Third People's Hospital Affiliated to Dalian Medical University from February 2021 to May 2021.The data from the right eye were collected for analysis.The patients were divided into SMILE group (40 patients, 40 eyes) and SPT-TransPRK group (52 patients, 52 eyes). Preoperative, 1- and 3-month postoperative visual acuity were measured to calculate the effectiveness, which was defined as the ratio of postoperative uncorrected visual acuity (UCVA) to preoperative best corrected visual acuity.Refraction was measured by an AR-1 autorefractor.Corneal higher-order aberration (HOA) including total HOA, spherical aberration and coma was measured by Sirius corneal topographer.Objective scatter index (OSI), modulation transfer function cut-off frequency (MTF cut-off), Strehl ratio (SR), simulated contrast visual acuity VA100 (day), VA20 (dusk) and VA9 (night) were measured via OQAS II visual quality analysis system.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Dalian Third People's Hospital Affiliated to Dalian Medical University (No.2019-KT-010). Written informed consent was obtained from each subject.Results:There was no significant difference in 3-month postoperative UCVA and effectiveness between the two groups ( Z=0.880, P=0.380; t=0.920, P=0.058). Patients in SPT-TransPRK group showed mild hyperopia 3 months after surgery.Preoperative, 1- and 3-month postoperative total corneal HOA was (0.47±0.18), (0.70±0.22) and (0.74±0.19)μm in SMILE group, and (0.40±0.14), (0.98±0.35) and (0.94±0.22)μm in SPT-TransPRK group respectively, showing statistically significant differences ( Fgroup=13.851, P=0.001; Ftime=29.960, P<0.001). Preoperative, 1- and 3-month postoperative spherical aberration was (-0.20±0.09), (-0.44±0.14) and (-0.44±0.15)μm in SMILE group, and (-0.20±0.10), (-0.71±0.23) and (-0.75±0.20)μm in SPT-TransPRK group respectively, showing statistically significant differences ( Fgroup=31.037, P<0.001; Ftime=48.005, P<0.001). The postoperative total corneal HOA and spherical aberration were increased in both groups compared with before surgery, with statistically significant differences (all at P<0.05). The 1- and 3-month postoperative total corneal HOA and spherical aberrations were smaller in SMILE group than in SPT-TransPRK group, and the differences were statistically significant (all at P<0.05). The 1- and 3-month postoperative coma were increased in both groups compared with before surgery, showing statistically significant differences (all at P<0.05). In SMILE group, 1-month postoperative OSI was higher and 1-month postoperative MTF cut-off, SR, and VA9 were lower than those before surgery, and 3-month postoperative OSI was higher and 3-month postoperative SR and VA9 were lower than those before surgery, showing statistically significant differences (all at P<0.05). In SPT-TransPRK group, 1-month postoperative OSI was higher and 1-month postoperative MTF cut-off, SR, VA100, VA20, and VA9 were lower than those before surgery, showing statistically significant differences (all at P<0.05). There was no significant difference in OSI, MTF cut-off, SR, VA100, VA20, and VA9 between 3 months postoperatively and before surgery in the SPT-TransPRK group (all at P>0.05). There was no significant difference in coma, OSI, MTF cut-off, SR, VA100, VA20, and VA9 between two groups (all at P>0.05). Conclusions:Both SMILE and SPT-TransPRK are effective methods for correcting myopia and they have comparable visual quality.Compared with SPT-TransPRK, corneal total HOA and spherical aberration are smaller after SMILE.

Objective:To explore the relationship between severe fever with thrombocytopenia syndrome virus (SFTSV) Gc and its N-glycosylation site and viral infectivity, a recombinant pseudovirus containing SFTSV Gc glycosylation site mutant was constructed.Methods:The eukaryotic expression vectors pcDNA3.1(+ )-GC, PCDNA3.1(+ )-GC(N291Q), PCDNA3.1(+ )-GC(N352Q) and PCDNA3.1(+ )-GC (N374Q) were constructed by site-directed mutagenesis and homologous recombination. After their successful expression in 293T cells, we infected VSVΔG-Fluc*G pseudovirus, constructed four recombinant pseudoviruses and tested their effects on the cell force of infection.Results:Double digestion identification and sequence determination confirmed the successful construction of eukaryotic expression vectors pcDNA3.1 (+ )-Gc, pcDNA3.1 (+ )-Gc(N291Q), pcDNA3.1 (+ )-Gc(N352Q) and pcDNA3.1 (+ )-Gc(N374Q). Indirect immunofluorescence and Western Blotting result indicated the successful expression of all the four recombinant plasmids. SFTSV Gc recombinant pseudoviruses are specific for infecting Vero cells. Pseudovirus infection capacity was decreased significantly after the glycosylation site mutation, and the mutant strain with the glycosylation site at position 352 had the lowest level of infectivity ( P<0.001, P=0.001). Conclusions:The glycosylation site of SFTSV Gc may be associated with the infectious effect of the viral infection, and the amino acid mutation at position 352 has the greatest effect on the viral infectivity.

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
COVID-19 ; Cohort Studies ; Hepatitis B, Chronic/epidemiology* ; Humans ; Retrospective Studies ; Risk Factors

Objective:To rescue enterovirus group A type 71 (EV-A71) VP1 protein mutant strain (Val147→Ala) and explore the effect of this locus on viral virulence.Methods:The SDLY107 constructed plasmid pMD19-T-EGFP-107 was used as template, the recombinant plasmid pMD19-T-EGFP-107 (VP1-1) was constructed by site-directed mutation and reverse genetics. The recombinant plasmid was transfected into BSR-T7/5 cells, and the transfection products were subcultured in RD cells for three times. The mutant strain SDLY-EGFP-107(VP1-1) was successfully saved. The viral replication was detected by qRT-PCR, and the cell damage caused by the virus was detected by cell proliferation (CCK-8) and lactate dehydrogenase (LDH) tests.Results:The target fragment was amplified by overlapping fusion PCR, and the size was about 3.4 kb. The recombinant plasmid was identified by double enzyme digestion and the mutation was verified by sequencing. Obvious fluorescence was observed 24 hours after transfection of BSR-T7/5 cells with recombinant plasmid and 24 hours after inoculation into RD cells. The replication ability of mutant strain SDLY107 (VP1-1) in RD cells was weaker than that of virulent strain SDLY107 ( t=9.58, P<0.001) by qRT-PCR. CCK-8 and LDH tests showed that the cytotoxicity of mutant strain SDLY-EGFP-107(VP1-1) in RD cells ( t=106.60, P<0.001; t=39.88, P<0.001), SH-SY5Y cells ( t=18.72, P<0.001; t=19.09, P<0.001) were significantly weaker than that of virulent strain SDLY107. Conclusions:The mutant strain SDLY-EGFP-107(VP1-1) was successfully saved, which confirmed that the mutation of the 147th amino acid site of VP1 protein could reduce the replication and cell damage of the virus, providing a basis for further study of the role of VP1 protein in the pathogenesis of EV-A71.

Objective:To explore the clinical strategies for preservation of the exposed implant in chronic wounds and wound repair.Methods:From January 2016 to January 2019, totally 8 patients (4 males and 4 females, aged 10 to 73 years) sustaining postoperative chronic wounds with exposed implants were admitted to the Fourth Medical Center of PLA General Hospital. There were 2 cases of abdominal patch exposure after abdominal trauma surgery, 2 cases of titanium plate exposure post craniocerebral surgery, 3 cases of internal fixator exposure post orthopedic surgery, and 1 case of cerebrospinal fluid drainage tube exposure after craniocerebral surgery. The wound exudate was collected for bacterial culture on admission. On the basis of glycemic control and correction of anemia and hypoproteinemia, thorough wound debridement was performed as soon as possible and the wound area after debridement ranged from 2.0 cm×0.5 cm to 6.0 cm×5.0 cm. The wounds of 4 patients were immediately closed after debridement, including 1 case by primary closure, 1 case by primary closure after local filling of platelet rich plasma gel, and 2 cases by local flap transplantation, with flap size of 10.0 cm×8.0 cm and 12.0 cm×8.0 cm, respectively. The donor sites of flaps were sutured directly and all the incisions were treated with continuous vacuum sealing drainage (VSD) after surgery. The other 4 patients were treated with continuous VSD after debridement to improve the wound bed. The wound of 1 case healed gradually, 1 case received direct wound suturing, and the wounds of 2 cases were repaired with thin split-thickness skin grafts from the thigh or the head. The results of bacterial culture of wound exudate on admission, wound healing post surgery, and follow-up were observed and recorded.Results:The bacterial culture of wound exudate on admission was positive in 6 patients, and 10 strains of bacteria were isolated with Staphylococcus epidermidis as the main pathogen. All the skin grafts or flaps of patients survived post surgery, with the incisions and wounds healed and all the implants preserved. After 1 to 3 years of follow-up, no recurrence of wound was found in any patient. Conclusions:The postoperative chronic wounds with exposed implants can be closed in primary stage by direct suturing or flap transplantation if it is clean enough on the basis of thorough debridement. The wounds with large defects or serious infection can be treated with continuous VSD firstly and then closed with direct suturing or skin grafting for delayed wound closure, thereby to reach the treatment goal of preserving the implants and repairing the wounds simultaneously.

Objective: To investigate the effects of platelet-rich plasma (PRP) combined with polylactic acid/polycaprolactone (PLA/PCL) on healing of mininature pig deep soft tissue defect caused by fragment injury. Methods: Two male Bama miniature pigs with 11 to 12 months (the same below) were selected by lottery to prepare PRP. The other twenty-seven male Bama miniature pigs were used to reproduce deep soft tissue defect caused by high-explosive ammunition fragment injury on bilateral posterior femoral region. According to the random number table, 27 pigs were divided into control group, material group, and PRP+material group, with 9 pigs in each group. After debridement, wounds of pigs in material group and PRP+material group were filled with PLA/PCL and PLA/PCL+2 mL activated PRP, respectively. Pigs in each group received suture of full-thickness skin to close the wounds. The operative duration was recorded. The length and volume of wounds of pigs in the above groups were measured immediately after surgery. In 1, 2, and 4 weeks after surgery, 3 pigs in each group were sacrificed to collect femoral wounds tissue on two sides, and PLA/PCL were collected from wounds of pigs in material group and PRP+material group for general observation of wounds tissue and degradation of the material. In 2 and 4 weeks after surgery, wounds tissue was obtained to observe the histological changes by hematoxylin-eosin staining, and expressions of transforming growth factor β (TGF-β) and vascular endothelial growth factor (VEGF), and angiogenesis were determined by immunohistochemical method. In 1, 2, and 4 weeks after surgery, wounds tissue was collected to determine mRNA expressions of TGF-β and VEGF by real-time quantitative reverse transcription polymerase chain reaction. Data were processed with analysis of variance of factorial design, one-way analysis of variance, and least significant difference-t test. Results: (1) There were no significantly statistical differences in length and volume of the wounds of pigs among the three groups (F=0.336, 0.282, P>0.05). The operative duration in control group [(30.9±2.1)min] was significantly shorter than that of material group [(39.7±2.2)min] and PRP+material group[(40.0±2.6)min], t=-11.45, -11.88, P<0.01. (2) There were respectively 10, 7, and 5 wounds tissue with infection in pigs of control group, material group, and PRP+material group. In 1, 2, 4 weeks after surgery, all of the wounds tissue of pigs was infected in control group, while none of wounds tissue of pigs was infected in material group and PRP+material group. In pigs of material group and PRP+material group, materials and tissue were easily separated in 1 week after surgery; some materials were integrated with tissue and showed a tendency of degradation in 2 weeks after surgery; materials were completely embedded with tissue in 4 weeks after surgery. (3) In pigs of control group, erythrocytes and inflammatory cells infiltration in wounds tissue were observed in 2 weeks after surgery, and necrotic tissue and inflammatory cells infiltration in wounds tissue were still observed in 4 weeks after surgery. In pigs of material group and PRP+material group, a large number of erythrocytes and inflammatory cells infiltration were observed in 2 weeks after surgery. Compared with that of material group, wounds tissue of pigs in PRP+material group had no inflammatory cells infiltration in 4 weeks after surgery. (4) Protein expressions of TGF-β in fibroblasts and multinuclear macrophagocytes, VEGF in fibroblasts and vascular endothelial cells, and blood vessel formation in wounds tissue of pigs in PRP+material group were significantly more than those of pigs in control group and material group in 2 and 4 weeks after surgery. (5) The mRNA expression of TGF-β in wounds tissue of pigs in material group was significantly higher than that in control group in 4 weeks after surgery (t=-3.93, P<0.01). Compared with those of pigs in control group and material group, the mRNA expression of TGF-β in wounds tissue of pigs in PRP+material group was significantly increased at each time point (t=9.23, 13.81, 11.73, -7.51, -12.04, -7.80, P<0.01). The mRNA expression of VEGF in wounds tissue of pigs increased significantly in material group compared with that of pigs in control group in 4 weeks after surgery (t=-3.94, P<0.01). Compared with those of pigs in control group and material group, the mRNA expression of VEGF in wounds tissue increased significantly in wound tissue of pigs in PRP+material group at each time point (t=12.33, 3.95, 7.97, -11.36, -2.97, -4.04, P<0.01). Conclusions PRP combined with PLA/PCL can accelerate wound healing of deep soft tissue defect of mininature pigs caused by fragment injury by providing physical scaffold for newborn tissue growth, promoting mRNA and protein expressions of TGF-β and VEGF.