Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To investigate the presence of pepsin and trypsin in the middle ear effusion of children with acute suppurative otitis media(ASOM).Methods Middle ear effusion samples were collected from 71 children with ASOM at Children's Hospital of Xuzhou.According to the characteristics of the middle ear effusions,the effu-sion was divided into serous and mucous types.The pH testing,Western Blotting(WB),and enzyme-linked immu-nosorbent assay(ELISA)were performed.Results ① There were 49.29％(35/71)of ASOM patients had a posi-tive RSI score(＞13).② The positive rate of pepsin in ASOM children was 49.29％(35/71),and the positive rate of trypsin was 42.25％(30/71).In addition,the positive rate of pepsin in RSI-positive children was 100％(35/35),and the positive rate of trypsin was 60％(21/35).There was no significant difference in the positive rate of pepsin and trypsin between serous and mucous middle ear effusion(P＞0.05).③ The pepsin concentration was 47.80(39.80,69.30)ng/ml and the trypsin concentration was 291.87±20.45 ng/ml in middle ear effusion of chil-dren with ASOM who had a positive WB test,and the trypsin concentration was significantly higher than pepsin(P＜0.05).There was no significant difference between the pepsin and the trypsin concentrations in serous and mu-cous middle ear effusion(P＞0.05).④ The pH value of mucous middle ear effusion was 7.39±0.28,and the pH value of serous middle ear effusion was 7.36±0.26.There was no significant difference between the pH value in se-rous and mucous middle ear effusion(P＞0.05).Conclusion The detection rates of pepsin and trypsin in middle ear effusion of children with ASOM were high which has important diagnostic value for children with ASOM combined with LPRD.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

Objective:To compare the results of thinned latissimus dorsi muscle flap combined with skin grafting and dorsal free flaps in repairing traumatic dorsal foot defects.Methods:From January 2005 to December 2019, 41 patients with large soft tissue defects in the dorsum of the foot were admitted to our department. Inclusion criteria: unilateral dorsal foot and ankle soft tissue defects, accompanied by tendon and/or bone exposure, cannot be repaired by simple methods such as skin grafting and local flaps, and the affected area has blood vessels that can be used for anastomosis. Exclusion criteria: primary or secondary vascular diseases, systemic conditions intolerant to prolonged surgery. According to the patient’s choices, the latissimus dorsi flap or the scapular flap were used for repair, namely the traditional flap group. Or latissimus dorsi muscle flap was used to fill and cover the defect, and then the surface of the muscle flap was sealed with split-thickness or full-thickness skin grafting, which is the combined transplantation group. Postoperative follow-up was mainly focused on the recovery of foot function, whether the shoes were worn normally, the appearance of the flap, and the rate of second operation.Results:A total of 41 patients were included in this study. All the flaps survived without infection and tissue necrosis. Twenty three cases, 16 males and 7 females, age from 6 to 52 years with an average of 27.6 years, were repaired with latissimus dorsi flap or scapula flap. The area of soft tissue defects was from 5.5 cm×8.0 cm to 19.5 cm×23.0 cm, with an average areaof 10.1 cm×16.2 cm. The follow-up time was from 6 to 24 months with an average of 9.7 months. All walking function of the foot was basically restored, and the texture of the flap was good. Eighteen patients had bloated flap appearance, 15 of which affected shoe-wearing, and 14 had debulking surgery, 2 had developed hypertrophic scar. Eighteen cases, 14 males and 4 females, age from 19 to 49 years with an average of 30.7 years, were repaired with latissimus dorsimuscle flap combined with split-thickness or full-thickness skin grafts. The area of soft tissue defects was from 4.0 cm×6.5 cm to 20.5 cm×23.0 cm, and the average area was 11.7 cm × 17.3 cm. All donor-site incisions are sutured in one stage without skin grafting. The follow-up time was from 4 to 20 months with an average of 8.3 months. The walking function of all operative feet, with good shape and without bloating, was basically restored. The contour and curve was similar to the healthy side and no skin injury and ulcer was observed. All patients were satisfied with wearing shoes and walking function, and no secondary surgery was required. However, 9 patients had developed hypertrophic scar.Conclusions:Compared with the traditional flap, the free latissimus dorsi muscle flap combined with skin grafting can effectively cover large area of soft tissue defect on the dorsal foot, without bloated flap appearance and secondary surgery. However, the risk of scar hyperplasia after combined transplantation increased.

Objective:To compare the results of thinned latissimus dorsi muscle flap combined with skin grafting and dorsal free flaps in repairing traumatic dorsal foot defects.Methods:From January 2005 to December 2019, 41 patients with large soft tissue defects in the dorsum of the foot were admitted to our department. Inclusion criteria: unilateral dorsal foot and ankle soft tissue defects, accompanied by tendon and/or bone exposure, cannot be repaired by simple methods such as skin grafting and local flaps, and the affected area has blood vessels that can be used for anastomosis. Exclusion criteria: primary or secondary vascular diseases, systemic conditions intolerant to prolonged surgery. According to the patient’s choices, the latissimus dorsi flap or the scapular flap were used for repair, namely the traditional flap group. Or latissimus dorsi muscle flap was used to fill and cover the defect, and then the surface of the muscle flap was sealed with split-thickness or full-thickness skin grafting, which is the combined transplantation group. Postoperative follow-up was mainly focused on the recovery of foot function, whether the shoes were worn normally, the appearance of the flap, and the rate of second operation.Results:A total of 41 patients were included in this study. All the flaps survived without infection and tissue necrosis. Twenty three cases, 16 males and 7 females, age from 6 to 52 years with an average of 27.6 years, were repaired with latissimus dorsi flap or scapula flap. The area of soft tissue defects was from 5.5 cm×8.0 cm to 19.5 cm×23.0 cm, with an average areaof 10.1 cm×16.2 cm. The follow-up time was from 6 to 24 months with an average of 9.7 months. All walking function of the foot was basically restored, and the texture of the flap was good. Eighteen patients had bloated flap appearance, 15 of which affected shoe-wearing, and 14 had debulking surgery, 2 had developed hypertrophic scar. Eighteen cases, 14 males and 4 females, age from 19 to 49 years with an average of 30.7 years, were repaired with latissimus dorsimuscle flap combined with split-thickness or full-thickness skin grafts. The area of soft tissue defects was from 4.0 cm×6.5 cm to 20.5 cm×23.0 cm, and the average area was 11.7 cm × 17.3 cm. All donor-site incisions are sutured in one stage without skin grafting. The follow-up time was from 4 to 20 months with an average of 8.3 months. The walking function of all operative feet, with good shape and without bloating, was basically restored. The contour and curve was similar to the healthy side and no skin injury and ulcer was observed. All patients were satisfied with wearing shoes and walking function, and no secondary surgery was required. However, 9 patients had developed hypertrophic scar.Conclusions:Compared with the traditional flap, the free latissimus dorsi muscle flap combined with skin grafting can effectively cover large area of soft tissue defect on the dorsal foot, without bloated flap appearance and secondary surgery. However, the risk of scar hyperplasia after combined transplantation increased.