Abstract Acne vulgaris is a common inflammatory skin disease associated with a colonization of Propionibacterium acnes ( P. acnes ), which can cause both physiological and psychological impact to the patients. Although antibiotic cream is commonly used to treat acne, limited transport of drug to the lesions within the pilosebaceous unit leads to poor bactericidal effect. Here, the authors described a new method of drug administration using a reactive oxygen species (ROS)‐responsive microneedle (MN) patch for anti‐acne therapy. Compared to the commonly used anti‐acne cream, enhanced efficacy toward dermis lesions can be achieved through the skin penetration by MNs. A controlled and sustained drug release in response to the over‐generated ROS within acne is also important for improving the antibacterial effect and reducing the side effects. In addition, the patch base, formed by hyaluronic acid (HA) and diatomaceous earth (DE) with high physical adsorption capability, is beneficial for accelerating healing of skin via the absorption of pus and dead cell debris. In vivo studies in a P. acnes ‐induced mouse model demonstrated this bioresponsive patch with adsorption capability could efficiently reduce the skin swelling and inhibit the bacterial growth.
Abstract Background This study is to describe the detailed design and surgical techniques of three-dimensional (3D)-printed custom-made endoprosthesis for hemipelvic tumorous bone defect. Methods According to the pelvic tumor resection classification by Enneking and Dunham, the hemipelvis is divided into three zones including the ilium (P1), acetabulum (P2), and pubis and ischium (P3). Thirteen patients were included in this study. Of these, P1 and P2 were involved in three cases, while P1, P2, and P3 were involved in 10. Based on radiography data, 3D pelvic model was rebuilt, and virtual surgery was simulated. Different fixation methods were applied according to residual bone volume. Parameters of the first sacral (S 1 ) vestibule, second sacral (S 2 ) vestibule, the narrowest zone of superior pubic medullary cavity (NPSPMC), and the resected surface of superior pubic medullary cavity (RSSPMC) were selectively measured in various fixation methods. Model overlapping, feature simplifying, and size controlling were three basic steps during design procedure. Volume proportion of porous structure was determined according to estimated weight of resected specimen. Acetabular location, anteversion, and inclination were modulated. Screw diameter, direction, and combination were considered. The osteotomy guides and plastic models were used during surgery. Results Of 13 cases, after P1 resection, endoprostheses were fixed to sacra (8; 61.5%), ilia (3; 23.1%), and both (2; 15.4%). After P3 resection, endoprostheses were fixed to residual acetabulum (3; 23.1%), and residual pubis by stem (8; 61.5%) or “cap-like” structure (2; 15.4%). Mean area of the S 1 vestibule, S 2 vestibule, RSSPMC, and PSPMC were 327.9 (222.2 to 400), 131.7 (102.6 to 163.6), 200.5 (103.8 to 333.2), and 79.8 mm 2 (40.4 to 126.2), respectively. Porous structure with 600 μm pore size and 70% porosity accounted for 68.8% (53.0 to 86.0) of the whole endoprosthesis on average. Mean acetabular anteversion and inclination were designed as 23.2° (20 to 25) and 42.4° (40 to 45). Median numbers of screws designed in the S 1 vestibule was 5 (IQR, 4 to 6), in the S2 vestibule was 1 (IQR, 1 to 2), in the ilium was 5 (IQR, 2 to 6), and in the pubis was 1 (IQR, 1 to 1), while screws designed in the ischium was all 2. Median number of screws inserted in the S 1 vestibule was 4 (IQR, 3 to 4), in the S 2 vestibule was 1 (IQR, 1 to 1), in the ilium was 3 (IQR, 1 to 5), in the pubis was 1 (IQR, 0 to 1), and in the ischium was 1 (IQR, 1 to 1). Conclusions This study firstly presents detailed design and related surgical techniques of 3D-printed custom-made hemipelvic endoprosthesis reconstruction. Osseointegration is critical for long-term outcome and requires three design elements including interface connection, porous structure, and initial stability achieved by precise matching and proper fixation methods.
Formula Le-Cao-Shi (LCS), a traditional Chinese medicine (TCM), has been used as folk remedy for treating hepatitis B for a long time. In our previous study, the anti-hepatitis B effects of LCS have been verified. In the present study, the anti-hepatitis B activities of LCS and its three single herbs were investigated in vitro by HepG2.2.15 cellular model, and the mechanisms against hepatitis B were deciphered via network pharmacology and gut microbiota analysis. By network pharmacology method, twelve key compounds that played a vital role in LCS were filtered from 213 ingredients. The targets RORA, CDK2, RELA, AKT1, IKBKG, PRKCβ and CASP3 were directly related to hepatitis B pathway, which indicated that LCS could exert anti-hepatitis B effect by co-regulating cell cycle and inflammatory pathways. The interactions between candidate compounds and target proteins that were directly involved in hepatitis B pathway were validated by molecular docking simulation and RT-PCR. By gut microbiota analysis, it was revealed that LCS could alter the disordered microbial composition in the infected ducks towards normal, especially the restoration of three key strains, namely Streptococcus alactolyticus, Enterococcus cecorum and Bacteroides fragilis. The above findings could provide a scientific basis for further development and utilization of LCS against hepatitis B.
Transcatheter aortic valve replacement (TAVR) has emerged as a revolutionary treatment for aortic stenosis. However, TAVR prices vary considerably, and factors associated with this variation remain unclear. We aim to describe the variation in TAVR prices in relation to hospital financial performance among institutions ranked by the U.S. News and World Report (USNWR). Using a modified two-part model, we examined financial and operational characteristics (TAVR performance scores, median all-payer within-hospital TAVR price, net hospital profit margin, hospital markups [i.e., charge-to-cost ratio], bed days available, and CMS wage index) of 640 TAVR-performing hospitals ranked by the USNWR. After determining observed to expected (O:E) ratios for TAVR prices for each hospital, we then examined hospital characteristics across O:E quintiles. Overall, price disclosure was 48.6% (n=311). Between the lowest and highest O:E quintiles, median hospital markup (4.75 vs 5.33; p=0.41) and median net hospital margin (1.76 vs 3.15; p=0.12) were comparable. The highest O:E ratio quintile had lower median TAVR prices compared to the lowest O:E ratio quintile ($72,129.12 vs $49,022.03; p<0.001). Most significantly, TAVR price IQR's within hospitals had a linear decline from the lowest to the highest O:E ratio quintiles ($119,043 vs $27,240; p<0.001). USNWR ranking scores had no significant variation across the quintiles (p=0.95). We concluded that hospitals that charge more than expected for TAVRs do not have higher profit margins nor markups and are not higher ranked by USNWR as those that charge less than expected. Additionally, with higher observed over expected TAVR prices, the variation in TAVR rates within hospitals decreased linearly. Finally, O:E TAVR price ratios appear to have no association with publicly reported hospital quality.
Insulin administration for the management of diabetes is accompanied by hypoglycemia, which is expected to be mitigated by glucose-responsive smart insulin that has self-regulation ability in response to blood glucose level (BGL) fluctuation. Here, we have prepared a new insulin analog by modifying insulin with forskolin (designated as insulin-F), a glucose-transporter (Glut) inhibitor. In vitro, insulin-F is capable of binding to Glut on erythrocyte ghosts, which can be inhibited by glucose and cytochalasin B. Upon subcutaneous injection in type 1 diabetic mice, insulin-F maintains BGLs below 200 mg mL-1 for up to 10 h, and achieves 20 h with two sequential injections. Moreover, insulin-F also binds to endogenous Gluts. Upon a glucose challenge, the elevated level of glucose competitively replaces and liberates insulin-F that binds to Glut, rapidly restoring BGLs to the normal range.
Abstract Rationale: Coblation of intervertebral disc is an effective and safe minimally invasive technology for treating discogenic pain. The inactivation of neural ingrowth around annulus and tissue ablation and coagulation are currently considered to be the major causes for success of this treatment. However, it has been found by clinical researchers that its long-term clinical outcome is not optimistic. This report has given us favorable information that this situation can be improved with multimodal therapy. Patient concerns: A 61-year-old man presented with right severe neck and shoulder pain in 2014 which could not be relieved by medications. Diagnoses: According to his symptoms and signs, this patient was diagnosed with cervical discogenic pain. And discography confirmed the diagnosis. Interventions: The patient underwent coblation of cervical intervertebral disc 4–5 (C4–5) and got apparently pain relief after surgery. After 1 month, he began to perform active exercise at least 30 min every day. Outcomes: The right neck and shoulder pain completely relieved for 4 years. The cervical lordosis of this patient was restored in 2018 which was confirmed by MRI compared in 2014 and NDI (neck disability index) decreased from 58 to 10%. Lessons: This report demonstrated that it was important and essential for clinicians to educate patients with discogenic pain to perform active exercise after minimally invasive surgery.
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