Retroperitoneal Nephrometry Scoring System (RETRO) for Minimal-Invasive Partial Nephrectomy.

PURPOSE: To propose a standardized scoring system of renal tumors suitable for partial nephrectomy based on mini-invasiveness and retroperitoneal approach. MATERIALS AND METHODS: One-hundred and five patients in retroperitoneal group were prospectively enrolled from January 2017 to December 2018. Perioperative characteristics of all patients were collected: age, gender, BMI, preoperative blood test and imaging results, operation time (the time period starts from the skin incision to the final skin closure), estimated blood lost, clamping time, complications within 30 days, American Society of Anesthesiologists (ASA) score, pathology. An algorithm was extracted, and it was used to predict the risk of complications. RESULTS: Symptoms, ASA score and RETRO score were significantly correlated to postoperative complications, excluding tumor size, ischemia time and operation time. Adjusted RETRO points were an independent factor to predict complication rate (p = 0.006). Limitation was that it did not analyze the relationship between the RETRO score and the long-term outcomes. CONCLUSION: The RETRO score simplifies the risk evaluation of partial nephrectomy for patients with renal tumor, especially benefits those surgeries performed under robot-assisted laparoscope via retroperitoneal approach. The new RETRO score system that we developed is a selection criterion to perform surgery via different approaches, and an accurate system to evaluate the complexity during partial nephrectomy.

Size-dependence of the skin penetration of andrographolide nanosuspensions: In vitro release-ex vivo permeation correlation and visualization of the delivery pathway.

Particle size is a key parameter to determine the capacity of nanoparticles to overcome the skin barrier; however, such effect and the possible mechanism remain only partially understood for nanosuspensions. In this work, we examined the skin delivery performance of andrographolide nanosuspensions (AG-NS) ranging in diameter from 250 nm to 1000 nm and analyzed the role of particle size in influencing their ability of skin penetration. The AG-NS with particle sizes of about 250 nm (AG-NS250), 450 nm (AG-NS450), and 1000 nm (AG-NS1000) were successfully prepared by ultrasonic dispersion method and characterized by transmission electron microscopy. The drug release and penetration via the intact and barrier-removed skin were compared by the Franz cell method, and the related mechanisms were probed using laser scanning confocal microscopy (LSCM) via visualization of penetration routes and histopathological study via observation of structural change of the skin. Our finding revealed that drug retention in the skin or its sub-layers was increased with the reduction of particle size, and the drug permeability through the skin also exhibited an obvious dependence on the particle size from 250 nm to 1000 nm. The linear relationship between the in vitro drug release and ex vivo permeation through the intact skin was well established among different preparations and in each preparation, indicating the skin permeation of the drug was mainly determined by the release process. The LSCM indicated that all these nanosuspensions could deliver the drug into the intercellular lipid space, as well as block the hair follicle in the skin, where a similar size dependence was also observed. The histopathological investigation showed that the formulations could make the stratum corneum of the skin loose and swelling without severe irritation. In conclusion, the reduction of particle size of nanosuspension would facilitate topical drug retention mainly via the modulation of drug release.

Nonporous versus Mesoporous Bioinspired Polydopamine Nanoparticles for Skin Drug Delivery.

The use of polydopamine-based bioinspired nanomaterials has shed new light on advanced drug delivery arising from their efficient surface functionalization. More recently, the polydopamine self-assemblies formed in two different modalities, i.e., nonporous and mesoporous nanoparticles, have begun to attract attention due to their expedient and versatile properties. However, their possibility for use in dermal drug delivery for local therapy, as well as their interaction with the skin, has not yet been demonstrated. Our study aimed to compare and explore the feasibility of the self-assembled nonporous polydopamine nanoparticles (PDA) and mesoporous polydopamine nanoparticles (mPDA) for local skin drug delivery. The formation of the PDA and mPDA structures was confirmed by the UV-vis-NIR absorption spectrum, the Fourier transform infrared spectroscopy, and the nitrogen adsorption/desorption isotherms. Using retinoic acid (RA) as the model drug, their effects on drug loading, release, photostability, skin penetration, and radical scavenging were investigated. Laser scanning confocal microscopy (LSCM) and hematoxylin and eosin (H&E) were introduced to probe their delivery routes and possible interaction with the skin. The results indicated that both PDA and mPDA could reduce the photodegradation of RA, and mPDA showed significantly better radical scavenging activity and drug loading capacity. The ex vivo permeation study revealed that both PDA and mPDA significantly enhanced the delivery of RA into the deep skin layers by comparison with the RA solution, in which follicular and intercellular pathways existed, and alteration in the structure of stratum corneum was observed. In light of drug loading capacity, size controllability, physical stability, as well as radical scavenging activity, mPDA was more preferable due to the improvement of these factors. This work demonstrated the feasibility and promising application of PDA and mPDA nanoparticles for dermal drug delivery, and the comparative concept of these two types of biomaterials can provide implications for their use in other fields.

ZIF-8 integrated with polydopamine coating as a novel nano-platform for skin-specific drug delivery.

Metal-organic frameworks (MOFs) are highly promising as a novel class of drug delivery carriers; however, there are few reports about their application in nanoparticle-based formulations for dermal administration. In this work, we developed a novel kind of nanoparticular system based on zeolitic imidazolate framework-8 (ZIF-8) and polydopamine (PDA) modification for improving the dermal delivery of 5-fluorouracil (5-FU). The structures and properties of the prepared nanoparticles were characterized using a variety of analytical methods. Their ex vivo delivery performance in the skin was investigated using Franz cells, and the underlying mechanisms were studied via confocal laser scanning microscopy (CLSM) and hematoxylin-eosin (HE) experiments which were employed to probe the penetration pathway and the interaction between nanoparticles and the skin. The results revealed that both 5-FU@ZIF-8 and ZIF-8@5-FU@PDA had an enhancement effect on the deposition of 5-FU in the skin, and the surface coating of PDA could further reduce drug permeation across the skin, especially in the case of impaired skin, in comparison with the drug solution. The CLSM study using rhodamine 6G as the fluorescent probe to mimic 5-FU indicated that ZIF-8 and ZIF-8@PDA could deliver their payloads into the skin via two pathways, i.e., intercellular and follicular ones, and the follicular route was shown to be particularly important for ZIF-8@PDA, in which the drug and carrier were co-delivered into the skin as an intact particle. This study provides evidence for using ZIF-8 and PDA modification for skin-specific drug delivery and offers an effective avenue to develop novel nanoplatforms for dermal application to treat skin diseases.

Light-related activities of metal-based nanoparticles and their implications on dermatological treatment.

Metal-based nanoparticles (MNPs) represent an emerging class of materials that have attracted enormous attention in many fields. By comparison with other biomaterials, MNPs own unique optical properties which make them a potential alternative to conventional therapeutic agents in medical applications. Especially, owing to the easy access to the skin, the use of MNPs based on their optical properties has gained importance for the treatment of a variety of skin diseases. This review provides an insight into the different optical properties of MNPs, including photoprotection, photocatalysis, and photothermal, and highlights their implications in treating skin disorders, with a special emphasis on their use in infection control. Finally, a perspective on the safety concern of MNPs for dermatological use is discussed and analyzed. The information gathered and presented in this review will help the readers have a comprehensive understanding of utilizing the photo-triggered activity of MNPs for the treatment of skin diseases.

Probing Pharmaceutical Strategies to Promote the Skin Delivery of Asiatic Acid from Hydrogels: Enhancement Effects of Organic Amine Counterions, Chemical Enhancers, and Microneedle Pretreatment.

Asiatic acid (AA) is a pentacyclic triterpene isolated from Centella asiatica, holding great promise for treating a variety of skin disorders. However, the dermal application of AA is limited by its poor solubility and permeability. This study aimed to identify a hydrogel formulation for AA and improve its skin penetration by various penetration enhancement methods. Four kinds of hydrogel bases were selected to prepare the AA hydrogel, in which different organic amines and chemical enhancers were incorporated in combination with microneedle pretreatment. The results showed that AA had good release profiles in the presence of hyaluronic acid as the hydrogel base and organic amines as the counter-ions. Diethylamine and Span 80 could promote drug penetration into the skin, and pretreatment with microneedles could further increase the drug permeability. In conclusion, the optimized hyaluronic acid hydrogel has great potential for use in the topical delivery of AA, and its penetration via the skin can be further improved by different pharmaceutical approaches.

Elucidating the particle size effect of andrographolide suspensions on their IVIVC performance in oral absorption.

The study aimed to explore the size effect on the in vitro-in vivo correlation (IVIVC) in the oral absorption of andrographolide nanosuspensions (Ag-NS). Ag-NS with controllable particle sizes were prepared by ultrasonic dispersion method, and the formulation and process parameters were optimized through single factor experiments using mean particle size, polydispersity index, and stability as evaluation indicators. The morphology of Ag-NS was observed by scanning electron microscopy (SEM), and the crystalline state of the nanosuspensions was characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The dissolution tests were carried out with the paddle method in two different mediums simulating the pH conditions in intestinal fluid (pH 6.8) and gastric fluid (pH 1.2), respectively. The pharmacokinetic behaviors were investigated in rats after oral administration, and a deconvolution approach was introduced to determine the correlation between in vitro dissolution and in vivo absorption (IVIVC). The formulation with the use of lecithin and PEG-800 as stabilizers showed its potential in the size-controllable preparation of Ag-NS. Via altering the ultrasonication amplitude and time, three Ag-NS suspensions with three particle sizes, i.e., Ag-NS 250 (249.8 ± 1.3 nm), Ag-NS 450 (485.2 ± 3.7 nm), Ag-NS 1000 (1015 ± 36.1 nm) were prepared. Their morphological and crystal characteristics were not changed during the size reduction process, but both of their in vitro dissolution and in vivo absorption were improved. Relatively better IVIVC performance was observed with the in vitro dissolution data at pH 6.8 (r > 0.9). With the reduction of particle size, the in vivo absorption fraction was more closed to the level of the in vitro dissolution. In conclusion, the decrease in particle size would improve the dissolution and absorption of Ag-NS, and also affect their IVIVC performance. The study would facilitate the design and quality control of Ag-NS in terms of particle size and dissolution specifications.

[Perioperative infection prevention strategies for double-lung transplantation in elderly patients with COVID-19].

OBJECTIVE: To summarize the experience of perioperative prevention during double-lung transplantation for elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Clinical data of 2 elderly patients with COVID-19 who underwent double-lung transplantation in the First Affiliated Hospital of Zhejiang University School of Medicine in March 2020 were retrospectively reviewed. Perioperative protective measures were introduced in terms of medical staffing, respiratory tract, pressure injuries, air in operating room, instruments and equipment, pathological specimens, and information management. RESULTS: Two cases of double-lung transplantation were successfully completed, and the patients had no operation-related complications. Extracorporeal membrane oxygenator was successfully removed 2 to 4 days after surgery and the patients recovered well. There was no infection among medical staff. CONCLUSIONS: Adequate preoperative preparation, complete patient transfer procedures, proper placement of instruments and equipment, strengthening of intraoperative care management, and attention to prevention of pressure injury complications can maximize the safety of COVID-19 patients and medical staff.

Clinical Efficacy of Immune Checkpoint Inhibitors in Older Non-small-Cell Lung Cancer Patients: A Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape among non-small-cell lung cancer (NSCLC) patients. The efficacy of ICI therapy in older patients (≥65 years) is controversial and not fully clarified. We performed a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced or metastatic NSCLC based on age (<65 years vs. ≥65 years). Methods: A comprehensive literature search for eligible randomized control phase II/III trials that compared the efficacy of anti-PD-1/PD-L1 agents against chemotherapy in advanced or metastatic NSCLC patients. Pooled overall survival (OS) and progression-free survival (PFS) estimates were calculated based on random/fixed effects models according to the heterogeneity between the studies. Results: A total of 10 studies involving 8 randomized controlled trials (2 updates) were enrolled in this meta-analysis [2,662 young patients (<65 years) and 1,971 older patients (≥65 years)]. The efficacy of anti-PD-1/PD-L1 agents is comparable between young (<65 years) and older (≥65 years) patients for OS [HR 0.75 95% CI (0.64-0.88) vs. 0.76 95% CI (0.66-0.87)]. However, our pooled analysis was not sufficient to show a significant benefit in terms of PFS for anti-PD-1/PD-L1 agents [HR 0.87 95% CI (0.74-1.01), P = 0.06]. In addition, we failed to see a PFS superiority of anti-PD-1/PD-L1 agents against chemotherapy in two age subgroups [<65 years and ≥65 years, HR 0.85 95% CI (0.72-1.01), P = 0.07 and HR 0.87 95% CI (0.68-1.10), P = 0.25]. Conclusion: ICIs therapy presents comparable efficacy in older advanced or metastatic NSCLC patients with young patients.

[A Prospective Study of Da Vinci Surgical Robotic System with Chest Wall External Nursing Interventions].

BACKGROUND: Minimally invasive and rapid recovery are trends in surgical treatment of lung cancer, and Da Vinci Surgical Robotic System plays an important role in them. This study was planned to explore the effect of chest wall external nursing interventions on reducing postoperative thoracic drainage and promoting rapid recovery of patients. METHODS: The patients who underwent robotic radical lung cancer resection in our hospital from November 2017 to April 2018were randomly divided into two groups. The control group received robotic radical lung cancer resection with abdominal bands wrapped around the chest. The experimental group underwent Da Vinci robotic radical lung cancer surgery and assisted chest wall external nursing interventions after surgery. RESULTS: The total and average daily drainage of the experimental group were less than those of the control group. Both the extubation time and the hospitalization time were shorter than those of the control group, but there was no significant difference. The pain score in the second days after operation of the experimental group was slightly higher than that of the control group, with no significant statistical difference. For patients whose chest wall thickness is less than 4 cm, mirabilite external application can significantly reduce the average daily and total drainage volume, but there is no significant difference in extubation time and hospitalization time. CONCLUSIONS: Chest wall external nursing interventions are beneficial to the recovery of patients undergoing Vinci robotic lung cancer surgery. Especially for patients with thinner chest wall. It can reduce postoperative drainage, shorten tube retention time and accelerate discharge. Further improvement is expected to achieve better clinical results.

Crystallization of Ge2Sb2Te5 thin films by nano- and femtosecond single laser pulse irradiation.

The amorphous to crystalline phase transformation of Ge2Sb2Te5 (GST) films by UV nanosecond (ns) and femtosecond (fs) single laser pulse irradiation at the same wavelength is compared. Detailed structural information about the phase transformation is collected by x-ray diffraction and high resolution transmission electron microscopy (TEM). The threshold fluences to induce crystallization are determined for both pulse lengths. A large difference between ns and fs pulse irradiation was found regarding the grain size distribution and morphology of the crystallized films. For fs single pulse irradiated GST thin films, columnar grains with a diameter of 20 to 60 nm were obtained as evidenced by cross-sectional TEM analysis. The local atomic arrangement was investigated by high-resolution Cs-corrected scanning TEM. Neither tetrahedral nor off-octahedral positions of Ge-atoms could be observed in the largely defect-free grains. A high optical reflectivity contrast (~25%) between amorphous and completely crystallized GST films was achieved by fs laser irradiation induced at fluences between 13 and 16 mJ/cm(2) and by ns laser irradiation induced at fluences between 67 and 130 mJ/cm(2). Finally, the fluence dependent increase of the reflectivity is discussed in terms of each photon involved into the crystallization process for ns and fs pulses, respectively.