Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial.

OBJECTIVE: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections. BACKGROUND: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent. METHODS: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections. The primary efficacy outcome was the clinical efficacy rate on the first day after ending the treatment (D8). The secondary efficacy outcome was the clinical efficacy rate on the fifth day posttreatment (D5), the bacteria clearance rate, and the overall efficacy rate at the mentioned 2 time points. The safety outcomes included adverse reactions and pharmacokinetic analysis posttreatment. RESULTS: A total of 220 patients from 27 hospitals in China were randomly assigned to 4 groups. On D8, the efficacy rate was 100.0%, 96.7%, 96.7% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 87.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). On D5, the efficacy rate was 100.0%, 93.4%, 98.3% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 82.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). The blood concentration of PL-5 was not detectable in pharmacokinetic analysis. No severe adverse event related to the application of PL-5 was reported. CONCLUSIONS: Antimicrobial peptide PL-5 spray is safe and effective for the treatment of skin wound infections. TRIAL REGISTRATION: ChiCTR2000033334.

Therapeutic strategies for retention of cranioplasty titanium mesh after mesh exposure.

BACKGROUND: Titanium mesh exposure after cranioplasty is a possible complication and is usually managed by mesh removal and flap transfer, but the advantages of the rigid prosthesis are then lost. This study aimed to present our experience with negative pressure wound therapy combined with soft tissue dilation for retaining the titanium mesh in patients with mesh exposure after cranioplasty. METHODS: This retrospective study included patients treated between 01/2016 and 05/2019 at the Jiangyin Hospital Affiliated to Southeast University School of Medicine. The wound was cleaned, and a cystic space was created for the tissue dilator, which was used with a self-designed negative pressure dressing. After the target dilation was achieved, the repair was conducted while retaining the titanium mesh. RESULTS: Eight patients were included (seven males and one female; 53.6 ± 8.8 (range, 43-65) years of age). The exposed mesh area ranged from 1 × 1 to 4 × 5.5 cm. The thinning scalp area around the exposed mesh ranged from 3.6 × 3.8 to 4 × 5.5 cm. Five patients had positive wound cultures and received sensitive antibiotics. The dilator embedding time was 20-28 days. The time of negative pressure wound therapy was 25-33 days. The hospital stay was 30-41 days. Primary wound healing was achieved in all eight patients. There were no signs of recurrence after 6-18 months of follow-up. The cranial CT scans were unremarkable. CONCLUSIONS: Negative pressure wound therapy combined with soft tissue dilation for exposed titanium mesh after cranioplasty might help retain the titanium mesh.

Chemical vapor deposition growth of sub-centimeter single crystal WSe2 monolayer by NaCl-assistant.

Monolayer WSe2 exhibits unique optical and electronic properties, showing great potential applications in functional integrated devices, such as electronic devices and optoelectronics. Understanding the growth behavior and process are the key points for the salt-assisted growth of large domain WSe2 monolayers, it is also very important for its further application in on-chip laser and opto-devices. Here, we report a NaCl-assistant method for controlled growth of single crystal monolayer WSe2 with a domain size up to 0.57 mm on SiO2/Si substrate. Atomic-resolution scanning transmission electron microscopy reveals that the Se1 and Se2 vacancy point defects are the main defect type of those materials. The growth behavior of the salt-assisted method have been systemly investigated. The loading mass of NaCl powder prefers to be less with the controllable vapor process. The flow of hydrogen gas was also preferred to be suitable with a weak etching effect. The morphology of monolayer WSe2 shows a sensitive temperature dependence evolution with the growth temperature increasing. A screw dislocation growth behavior with 15° angle is also observed with the NaCl-assistant method. The results provide a deep understanding of the mechanism for the NaCl-assistant growth of large size monolayer WSe2.

Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial.

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.

Modeling and Simulation of Autonomous Inflow Control Devices for Gas Exploitation.

Horizontal well technology is an efficient method of oil and gas exploitation. The goal of increasing oil production and improving productivity can be achieved by increasing the contact area between the reservoir and the wellbore. The presence of bottom water cresting reduces the efficiency of oil and gas production significantly. Autonomous inflow control devices (AICDs) are widely used to delay the influx of water into the wellbore. Two kinds of AICDs are proposed to restrain the bottom water breakthrough during natural gas production. The fluid flows in the AICDs are simulated numerically. The pressure difference between the inlet and outlet is calculated to evaluate the ability of blocking the flow. A dual-inlet design can increase the flow rate of AICDs, thus enhancing the water blocking effect. Numerical simulations show that the devices can block water flowing into the wellbore effectively.

Fluorinated Covalent Organic Framework-Based Nanofluidic Interface for Robust Lithium-Sulfur Batteries.

To realize the practical application of lithium-sulfur (Li-S) batteries, there is a need to inhibit uncontrolled Li deposition by facilitating Li-ion migration, and suppress the irreversible consumption of cathodes by preventing polysulfide shuttling. However, a permselective artifical membrane or interlayer which features fast ion transport but low polysulfide crossover is elusive. Here, we report the design and synthesis of a fluorinated covalent organic framework (4F-COF)-based membrane with a high permselectivity and increased battery lifespan. Combining density functional theory calculation, molecular dynamic simulation, and in situ Raman analysis, we demonstrate that fluorinated COF eliminates polysulfides shutting and dendritic lithium formation. Consequently, Li symmetrical cells demonstrate Li plating/stripping behaviors for 2000 h under 1 mA cm-2. More importantly, Li-S batteries based on the 4F-COF/PP separator achieve cycling retention of 82.3% over 1000 cycles at 2 C, rate performance of 568.0 mA h g-1 at 10 C, and an areal capacity of 7.60 mA h cm-2 with a high sulfur loading (∼9 mg cm-2). This work demonstrates that functionalizing nanochannels in COFs can impart permselectivity for energy storage applications.

The burden of skin and subcutaneous diseases: findings from the global burden of disease study 2019.

Background: The small number of existing integrative studies on the global distribution and burden of all types of skin and subcutaneous diseases hinders relevant comparisons. Objective: This study aimed to determine the latest distribution, epidemiological differences, and factors potentially influencing each skin and subcutaneous disease and the policy implications. Methods: Data on the skin and subcutaneous diseases were obtained from the Global Burden of Disease Study 2019. The incidence, disability-adjusted life years (DALYs), and deaths due to skin and subcutaneous diseases in 204 countries and regions from 1990 to 2019 were analyzed and stratified by sex, age, geographical location, and sociodemographic index (SDI). The annual age-standardized rate of change in the incidence was obtained to evaluate temporal trends. Results: Of 4,859,267,654 (95% uncertainty interval [UI], 4,680,693,440-5,060,498,767) new skin and subcutaneous disease cases that were identified, most were fungal (34.0%) and bacterial (23.0%) skin diseases, which accounted for 98,522 (95% UI 75,116-123,949) deaths. The burden of skin and subcutaneous diseases measured in DALYs was 42,883,695.48 (95%UI, 28,626,691.71-63,438,210.22) in 2019, 5.26% of which were years of life lost, and 94.74% of which were years lived with disability. The highest number of new cases and deaths from skin and subcutaneous diseases was in South Asia. Globally, most new cases were in the 0-4-year age group, with skin and subcutaneous disease incidence slightly higher in men than in women. Conclusion: Fungal infections are major contributors to skin and subcutaneous diseases worldwide. Low-middle SDI states had the highest burden of skin and subcutaneous diseases, and this burden has increased globally. Targeted and effective management strategies based on the distribution characteristics of each country are, thus, required to reduce the burden of skin and subcutaneous diseases.

[Influence of the depth of retained denatured dermis on the survival rate of grafted skin in burn swine with deep partial-thickness burn].

OBJECTIVE: To explore the influence of the thickness of retained denatured dermis on the survival rate of grafted skin in swine with deep partial-thickness burn. METHODS: Four deep partial-thickness wounds were reproduced respectively on both sides of spine in 7 Chinese domestic pigs. The wounds of 6 pigs were divided into 0.25, 0.50, 0.75, and 1.00 mm groups with 12 wounds in each group according to the random number table. Tangential excision and auto-skin grafting were performed. Before the tangential excision, 1 tissue specimen was harvested from the center of each remaining wound for the estimation of the depth of burn, and histological observation was done. After the tangential excision, 1 tissue specimen was harvested from the area near the center of each wound for the measurement of the depth of retained denatured dermis with histological examination. The 8 wounds of one pig were set as the control group, and the operation was done, and then they were treated with exposure treatment after biopsy specimens were taken with above-mentioned method. The general condition of wounds in 5 groups was observed from immediately after injury to post injury month (PIM) 3. On post injury day (PID) 7, the survival rate of grafted skin was observed in 0.25, 0.50, 0.75, and 1.00 mm groups. Wound healing time was recorded. At PIM 3, the specimens were harvested from the wounds of 5 groups, and their ultra microstructures were observed by transmission electron microscope. Data were processed with rank-sum test, one-way analysis of variance, and LSD test. RESULTS: The depth of the burn tissue was (1.120 ± 0.211) mm. The depths of retained denatured dermis in 0.25, 0.50, 0.75, and 1.00 mm groups were respectively (0.830 ± 0.031), (0.701 ± 0.010), (0.382 ± 0.031), and (0.141 ± 0.040) mm. At PID 8, all grafted skin in 0.25 and 0.50 mm groups became necrotic; most grafted skin in 0.75 mm group was necrotic; most grafted skin in 1.00 mm group survived with only a few became necrotic and separated from the wounds. The scabs were gradually separated from the wounds of control group. On PID 15, the grafted skin which did not survive in 0.25, 0.50, and 0.75 mm groups was gradually separated from the wounds with exudate forming scab on the surface in varying degrees, while the wounds in 1.00 mm group were all healed, and the incidence of scabs formation was highest in control group. At PIM 3, scar contraction was found in 0.25, 0.50, 0.75 mm groups and control group, while no obvious scar was observed in 1.00 mm group. There were statistically significant differences in the survival rate of grafted skin in 0.25, 0.50, 0.75, and 1.00 mm groups (χ(2) = 19.421, P < 0.001). The survival rate was the highest in 1.00 mm group [70% (60%, 80%)], while the survival rate was 20% (0, 30%) in 0.75 mm group, and it was in both 0.25 and 0.50 mm groups with non-survival of all the grafted skin. There were statistically significant differences in the wound healing time among 5 groups (F = 41.450, P < 0.001). The wound healing time in 0.25 and 0.50 mm groups were respectively (18.2 ± 1.5), and (18.7 ± 2.3) d, not statistically significant different from that of control group [(18.4 ± 1.7) d, P values both above 0.05]. The wound healing time in 0.75 mm group [(14.9 ± 2.6) d] was significantly different from those of 0.25, 0.50 mm groups and control group (P values all below 0.01). The wound healing time in 1.00 mm group [(9.5 ± 1.2) d] was significantly shorter compared with that of the other 4 groups (P values all below 0.01). Before tangential excision, the zone of infiltration of the inflammatory cells was observed in the deep dermis of wounds in 5 groups. After tangential excision and before auto-skin grafting, the depth from the fault surface to the zone of infiltration of the inflammatory cells varied in 0.25, 0.50, 0.75, and 1.00 mm groups while more inflammatory cells were observed in control group. At PIM 3, many fibroblasts were observed in the dermis of wounds in 1.00 mm group with abundant rough endoplasmic reticulum and basically intact organelles. CONCLUSIONS: Performing autologous skin grafting on deep partial-thickness burn, in which the depth of retained denatured dermis was 0.10 mm, may help regenerate dermal function and alleviate scar formation.