[Effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride hydrogel in the repair of infected full-thickness skin defect wounds in mice].

Objective: To investigate the effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride (GelMA) hydrogel (hereinafter referred to as composite hydrogel) in the repair of infected full-thickness skin defect wounds in mice. Methods: This study was an experimental study. Cerium oxide nanoenzyme with a particle size of (116±9) nm was prepared by hydrothermal method, and GelMA hydrogel with porous network structure and good gelling performance was also prepared. The 25 µg/mL cerium oxide nanoenzyme which could significantly promote the proliferation of human skin fibroblasts and had high superoxide dismutase activity was screened out. It was added to GelMA hydrogel to prepare composite hydrogel. The percentage of cerium oxide nanoenzyme released from the composite hydrogel was calculated after immersing it in phosphate buffer solution (PBS) for 3 and 7 d. The red blood cell suspension of mice was divided into PBS group, Triton X-100 group, cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group, which were treated with corresponding solution. The hemolysis of red blood cells was detected by microplate reader after 1 h of treatment. The bacterial concentrations of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were determined after being cultured with PBS, cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h. The sample size in all above experiments was 3. Twenty-four 8-week-old male BALB/c mice were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back and infected with MRSA. The mice were divided into control group without any drug intervention, and cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group applied with corresponding solution, with 6 mice in each group. The wound healing was observed on 3, 7, and 14 d after injury, and the remaining wound areas on 3 and 7 d after injury were measured (the sample size was 5). The concentration of MRSA in the wound exudation of mice on 3 d after injury was measured (the sample size was 3), and the blood flow perfusion in the wound of mice on 5 d after injury was observed using a laser speckle flow imaging system (the sample size was 6). On 14 d after injury, the wound tissue of mice was collected for hematoxylin-eosin staining to observe the newly formed epithelium and for Masson staining to observe the collagen situation (the sample size was both 3). Results: After immersion for 3 and 7 d, the release percentages of cerium oxide nanoenzyme in the composite hydrogel were about 39% and 75%, respectively. After 1 h of treatment, compared with that in Triton X-100 group, the hemolysis of red blood cells in PBS group, GelMA hydrogel group, cerium oxide nanoenzyme group, and composite hydrogel group was significantly decreased (P<0.05). Compared with that cultured with PBS, the concentrations of MRSA and Escherichia coli cultured with cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h were significantly decreased (P<0.05). The wounds of mice in the four groups were gradually healed from 3 to 14 d after injury, and the wounds of mice in composite hydrogel group were all healed on 14 d after injury. On 3 and 7 d after injury, the remaining wound areas of mice in composite hydrogel group were (29±3) and (13±5) mm2, respectively, which were significantly smaller than (56±12) and (46±10) mm2 in control group and (51±7) and (38±8) mm2 in cerium oxide nanoenzyme group (with P values all <0.05), but was similar to (41±5) and (24±9) mm2 in GelMA hydrogel group (with P values both >0.05). On 3 d after injury, the concentration of MRSA on the wound of mice in composite hydrogel group was significantly lower than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively (with P values all <0.05). On 5 d after injury, the volume of blood perfusion in the wound of mice in composite hydrogel group was significantly higher than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively (P<0.05). On 14 d after injury, the wound of mice in composite hydrogel group basically completed epithelization, and the epithelization was significantly better than that in the other three groups. Compared with that in the other three groups, the content of collagen in the wound of mice in composite hydrogel group was significantly increased, and the arrangement was also more orderly. Conclusions: The composite hydrogel has good biocompatibility and antibacterial effect in vivo and in vitro. It can continuously sustained release cerium oxide nanoenzyme, improve wound blood perfusion in the early stage, and promote wound re-epithelialization and collagen synthesis, therefore promoting the healing of infected full-thickness skin defect wounds in mice.

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia].

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

[Clinical effects of free transplanted pre-expanded scapular flap in reconstructing scar contracture deformity of neck].

Objective: To investigate the clinical effects of free transplanted pre-expanded scapular flap in reconstructing scar contracture deformity of neck. Methods: A retrospective observational study was conducted. From February 2010 to August 2020, 17 cervical scar deformity patients (9 males and 8 females, aged 8-42 years) who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University. The patients underwent skin and soft tissue expander (hereinafter referred to as expander) implantation in scapular region in stage Ⅰ procedures, and the free transplanted pre-expanded flaps were used to resurface the wounds followed by neck scar resection in the stage Ⅱ procedures. The wound size after neck scar release was 12.0 cm×6.0 cm-30.0 cm×24.0 cm, and the size of the flap ranged from 13.0 cm×7.5 cm to 31.5 cm×25.0 cm. The wounds in donor site of 15 patients were sutured directly, and the wounds in donor site of 2 patients were covered with full-thickness skin graft from abdominal area. The survival of flaps was observed after the operation of stage Ⅱ. Six months after stage Ⅱ surgery, Z plasty was performed to treat the incision scar contracture in 2 patients. For the 5 patients of overweight or bloating appearance in the 1/3 proximal flap underwent debulking procedures in 6-9 months after stage Ⅱsurgery. Before the stage Ⅰ surgery and six months after the last procedure (stage Ⅱ or stage Ⅲ), mental cervical angle (MCA) and cervical mandibular angle (CMA) were measured and the improvement of neck scar was evaluated by the angle values. The cervical motor function, skin color and texture in recipient areas, and scar in the donor sites assessed by Vancouver scar scale (VSS) were observed during follow-up. Data were statistically analyzed with paired sample t test. Results: After stage Ⅱ surgery, 15 patients' flaps survived well; venous crisis occurred in 2 flaps within 24 h after operation, and the flaps survived well after emergency exploration and thrombus removal+vascular re-anastomosis. Compared with the angle values of MCA of (126±12)° and CMA of (148±13)° of patients before the stage Ⅰ surgery, the angle values of MCA of (107±12)° and CMA of (123±11)° of patients in six months after the last procedure were significantly decreased (with t values of 10.68 and 6.54, respectively, P<0.05). After 2 years of follow-up, the patient's neck dorsiflexion, lateral bending, or other motor functions were not restricted; the color and texture of the flap in recipient site were close to those of the normal neck skin; the patient cases with VSS scores of scarring of 3, 4, 5, 6, and 7 were 1, 3, 7, 5, and 1 case, respectively. Conclusions: The free transplantation of the pre-expanded scapular flaps can provide sufficient tissue for wound coverage after the release of cervical scar contracture deformity; the expanded skin tissue is featured by thin soft tissue and good pliability, which is conducive to restore the neck appearance; the donor sites are relatively covert with less tension, therefore, the treatment is an effective method for correcting the contracture in the neck.

[Clinical effects of follicle unit extraction transplantation combined with recombinant bovine basic fibroblast growth factor and minoxidil in the treatment of secondary cicatricial alopecia].

Objective: To explore the clinical effects of follicle unit extraction (FUE) transplantation combined with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel and minoxidil tincture in treating secondary cicatricial alopecia (hereinafter referred to as cicatricial alopecia). Methods: A retrospective observational study was conducted. According to the different treatment methods, 50 cicatricial alopecia patients who met the inclusion criteria and only underwent FUE transplantation in the First Affiliated Hospital of Air Force Medical University from March 2013 to April 2017 were recruited into FUE alone group (26 males and 24 females, aged (28±13) years), and 50 cicatricial alopecia patients who met the inclusion criteria and underwent FUE transplantation+rb-bFGF gel during 1 to 14 days after surgery+minoxidil tincture during 15 to 180 days after surgery in this hospital from May 2017 to April 2020 were recruited into FUE+rb-bFGF+minoxidil group (32 males and 18 females, aged (27±9) years). Hair loss rates in post surgery month (PSM) 3 and 6, hair survival rates and satisfaction rates of patients in PSM 12, and the adverse effect rates of patients in the 2 groups within PSM 12 were observed and calculated. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and independent sample t test. Results: In PSM 3 and 6, the hair loss rates of patients in FUE alone group were significantly higher than those in FUE+rb-bFGF+minoxidil group, respectively (t=70.850, 42.610, P<0.01). In PSM 12, the hair survival rate of patients in FUE+rb-bFGF+minoxidil group was (91.0±2.8)%, which was significantly higher than (80.9±6.9)% in FUE alone group (t=9.665, P<0.01). In PSM 12, 25 patients were very satisfied, 12 patients were fairly satisfied, 10 patients were slightly satisfied, 2 patients were not satisfied, and 1 patient was very unsatisfied in FUE alone group; 42 patients were very satisfied, 5 patients were fairly satisfied, and 3 patients were slightly satisfied in FUE+rb-bFGF+minoxidil group. The satisfaction rate of patients in FUE alone group was 74% (37/50), which was significantly lower than 94% (47/50) in FUE+rb-bFGF+minoxidil group (P<0.01). Within PSM 12, compared with those in FUE+rb-bFGF+minoxidil group, the incidence rates of folliculitis, abnormal growth direction, and skin necrosis in transplant site were not obviously changed in FUE alone group (P>0.05), while the incidence of scar in donor site was significantly higher (P<0.05). Conclusions: Compared with FUE transplantation alone, FUE transplantation combined with rb-bFGF and minoxidil can reduce the hair loss rate, improve the hair survival rate and the satisfaction rate of patients with cicatricial alopecia after FUE transplantation, with less adverse effects, thus are good for cicatricial alopecia treatment.

[Clinical effects of fine follicular unit extraction and transplantation in repairing cicatricial eyebrow defects].

Objective: To observe the clinical effects of fine follicular unit extraction (FUE) and transplantation in repairing cicatricial eyebrow defects. Methods: The retrospective observational study was conducted. From September 2013 to January 2020, 58 patients (36 males and 22 females, aged 12-40 years) underwent fine FUE and transplantation to treat cicatricial eyebrow defects in the First Affiliated Hospital of Air Force Medical University. The hair survival rate in 10 months post operation was observed and calculated, and the curative effect was graded. Visual Analogue Scale was used to evaluate patients' satisfaction in one year post operation. The adverse reactions during operation and within one year post operation were recorded, and the adverse reaction incidence was calculated. Results: The hair survival rate of 58 patients in 10 months post operation was (84±5)%. Four patients (6.9%) had good curative effect, 54 patients (93.1%) had excellent curative effect in effect evaluation. Four patients (6.90%) were moderately satisfied, 5 patients (8.62%) were fairly satisfied, and 49 patients (84.48%) were very satisfied in satisfaction evaluation. Twelve patients had 14 adverse reactions, with an incidence of 24.14%. Conclusions: Fine FUE and transplantation can provide good cosmetic results for patients with cicatricial eyebrow defects, with high satisfaction of patient and few adverse reactions.

Absence of Magnetic Thermal Conductivity in the Quantum Spin Liquid Candidate EtMe_{3}Sb[Pd(dmit)_{2}]_{2}.

We present the ultralow-temperature specific heat and thermal conductivity measurements on single crystals of triangular-lattice compound EtMe_{3}Sb[Pd(dmit)_{2}]_{2}, which has long been considered as a gapless quantum spin liquid candidate. In specific heat measurements, a finite linear term is observed, consistent with the previous work [S. Yamashita et al., Nat. Commun. 2, 275 (2011)NCAOBW2041-172310.1038/ncomms1274]. However, we do not observe a finite residual linear term in the thermal conductivity measurements, and the thermal conductivity does not change in a magnetic field of 6 T. These results are in sharp contrast to previous thermal conductivity measurements on EtMe_{3}Sb[Pd(dmit)_{2}]_{2} [M. Yamashita et al., Science 328, 1246 (2010)SCIEAS0036-807510.1126/science.1188200], in which a huge residual linear term was observed and attributed to highly mobile gapless excitations, likely the spinons of a quantum spin liquid. In this context, the true ground state of EtMe_{3}Sb[Pd(dmit)_{2}]_{2} has to be reconsidered.

Discrete Superconducting Phases in FeSe-Derived Superconductors.

A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.

Comparative study of the Triton X-100-sodium deoxycholate method and detergent-enzymatic digestion method for decellularization of porcine aortic valves.

BACKGROUND: Valve replacement is the primary surgical treatment for heart valve disease. However, the clinical benefit of biological valve substitutes is limited by their potential immunogenicity. AIM: To seek a better method of preparing biological scaffolds for tissue engineering heart valves, we compared the ability of different decellularization procedures to remove cells and maintain the scaffold structure. MATERIALS AND METHODS: Specimens of fresh porcine aortic valve leaflets were randomly divided into group I (n = 16), group II (n = 16) and group III (n = 16). The valve leaflets in group I were not decellularized; group II were treated with Triton X-100 and sodium deoxycholate; and group III were treated by a detergent-enzymatic digestion method. The valve leaflets were investigated by gross examination, hematoxylin-eosin staining, Masson's trichrome staining, and scanning electron microscopy to observe the valve structure and the integrity of collagen and elastin. The DNA content was measured to confirm the removal of cells. RESULTS: The detergent-enzymatic digestion method completely removed cells and led to valve fiber structural alterations in group III. The Triton X-100-sodium deoxycholate method achieved both complete decellularization and preservation of the valve fiber structure in group II. CONCLUSIONS: The detergent-enzymatic digestion method is a better technique for decellularization than the Triton X-100-sodium deoxycholate method, as it enables both complete decellularization and preservation of the valve scaffold structure.

Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells.

Transforming growth factor-beta1 (TGF-beta1) can activate mitogen-activated protein kinases (MAPKs) in many types of cells. The mechanism of this activation is not well elucidated. Here, we explore the role of TGF-beta/Smads signaling compounds in TGF-beta1-mediated activation of extracellular signal-regulated kinase (ERK) MAPK in human papillomavirus (HPV)-18 immortalized human bronchial epithelial cell line BEP2D and the role of TGF-beta1-induced phosphorylation of ERK in proliferation and apoptosis of BEP2D. The cell models of siRNA-mediated silencing of TGF-beta receptor type II (TbetaRII), Smad2, Smad3, Smad4, and Smad7 were employed in this study. Our results demonstrate that TGF-beta1 activates ERK in a time-dependent manner with a maximum effect at 60 min; overexpression of Smad7 increased this TGF-beta1-mediated phosphorylation of the ERK; and siRNA-mediated silencing of TbetaRII, Smad3, Smad4, and Smad7 abrogated this effect. Moreover, we observed that overexpression of Smad7 restored TGF-beta1-mediated ERK phosphorylation in Smad4 knockdown cells but not in TbetaRII knockdown cells. In BEP2D cells, TGF-beta1 treatment effectively inhibited cells' proliferation and induced their apoptosis. Pretreatment with U0126, an inhibitor of ERK1/2, significantly enhanced the TGF-beta1-mediated antiproliferative and apoptosis induction effects in BEP2D cells. These data revealed that TbetaRII and Smad7 play the critical roles in TGF-beta1-mediated activation of ERK; Smad3 and Smad4 can play an indirect role through up-regulating Smad7 expression; and TGF-beta1-induced phosphorylation of ERK may participate in BEP2D cell proliferation and apoptosis regulation.