Development of novel hybrid 3D-printed degradable artificial joints incorporating electrospun pharmaceutical- and growth factor-loaded nanofibers for small joint reconstruction.

Small joint reconstruction remains challenging and can lead to prosthesis-related complications, mainly due to the suboptimal performance of the silicone materials used and adverse host reactions. In this study, we developed hybrid artificial joints using three-dimensional printing (3D printing) for polycaprolactone (PCL) and incorporated electrospun nanofibers loaded with drugs and biomolecules for small joint reconstruction. We evaluated the mechanical properties of the degradable joints and the drug discharge patterns of the nanofibers. Empirical data revealed that the 3D-printed PCL joints exhibited good mechanical and fatigue properties. The drug-eluting nanofibers sustainedly released teicoplanin, ceftazidime, and ketorolac in vitro for over 30, 19, and 30 days, respectively. Furthermore, the nanofibers released high levels of bone morphogenetic protein-2 and connective tissue growth factors for over 30 days. An in vivo animal test demonstrated that nanofiber-loaded joints released high concentrations of antibiotics and analgesics in a rabbit model for 28 days. The animals in the drug-loaded degradable joint group showed greater activity counts than those in the surgery-only group. The experimental data suggest that degradable joints with sustained release of drugs and biomolecules may be utilized in small joint arthroplasty.

Case report: Cryoablation as a novel bridging strategy prior to CAR-T cell therapy for B cell malignancies with bulky disease.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a powerful immunotherapy in relapsed/refractory (R/R) hematological malignancies, especially in R/R B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). To prevent disease progression and reduce tumor burden during CAR-T cell manufacturing, bridging therapies prior to CAR-T cell infusion are crucial. At present, it has been demonstrated that targeted therapy, radiotherapy and autologous stem cell transplantation (ASCT) could serve as effective bridging strategies. However, whether cryoablation could serve as a novel bridging strategy is unknown. In this paper, we report 2 cases of R/R B cell malignancies with bulky disease that were successfully treated with a combination of cryoablation and CAR-T cell therapy. Patient 1 was a 65-year-old female who was diagnosed with R/R MM with extramedullary disease (EMD). She was enrolled in the anti-BCMA CAR-T cell clinical trial. Patient 2 was a 70-year-old man who presented with a subcutaneous mass in the right anterior thigh and was diagnosed with primary cutaneous diffuse large B cell lymphoma, leg type (PCLBCL-LT) 1 year ago. He failed multiline chemotherapies as well as radiotherapy. Thus, he requested anti-CD19 CAR-T cell therapy. Unfortunately, they all experienced local progression during CAR-T cell manufacturing. To rapidly achieve local tumor control and reduce tumor burden, they both received cryoablation as a bridging therapy. Patient 1 achieved a very good partial response (VGPR) 1 month after CAR-T cell infusion, and patient 2 achieved a partial response (PR) 1 month after CAR-T cell infusion. In addition, adverse effects were tolerable and manageable. Our study demonstrated the favorable safety and efficacy of combination therapy with cryoablation and CAR-T cell therapy for the first time, and it also indicates that cryoablation could serve as a novel therapeutic strategy for local tumor control in B cell malignancies.

An injectable gelatin/sericin hydrogel loaded with human umbilical cord mesenchymal stem cells for the treatment of uterine injury.

Abnormal endometrial receptivity is a major cause of the failure of embryo transplantation, which may lead to infertility, adverse pregnancy, and neonatal outcomes. While hormonal treatment has dramatically improved the fertility outcomes in women with endometriosis, a substantial unmet need persists in the treatment. In this study, methacrylate gelatin (GelMA) and methacrylate sericin (SerMA) hydrogel with human umbilical cord mesenchymal stem cells (HUMSC) encapsulation was designed for facilitating endometrial regeneration and fertility restoration through in situ injection. The presented GelMA/10%SerMA hydrogel showed appropriate swelling ratio, good mechanical properties, and degradation stability. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell encapsulation ability of HUMSC. Further in vivo experiments demonstrated that GelMA/SerMA@HUMSC hydrogel could increase the thickness of endometrium and improve the endometrial interstitial fibrosis. Moreover, regenerated endometrial tissue was more receptive to transfer embryos. Summary, we believed that GelMA/SerMA@HUMSC hydrogel will hold tremendous promise to repair or regenerate damaged endometrium.

Adverse Events of Sacubitril/Valsartan: A Meta-analysis of Randomized Controlled Trials.

ABSTRACT: This review aimed to summarize the adverse events (AEs) reported during the use of sacubitril/valsartan versus angiotensin converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB). Studies containing safety outcomes or AEs during the use of sacubitril/valsartan versus ACEI/ARB were retrieved from the MEDLINE, Embase, and Cochrane Library databases and clinical trials. From the selected studies, the pooled risk ratios with 95% confidence intervals of dichotomous outcomes were assessed by a random or fixed effects model in our meta-analysis. Fourteen studies involving 20,261 patients were included in this review. No significant differences were found in total AEs between the sacubitril/valsartan and ACEI/ARB groups. Compared with ACEI/ARB, sacubitril/valsartan decreased the risk of death, discontinuation due to AEs, and renal dysfunction, whereas it increased the risk of hypotension. Specifically, sacubitril/valsartan decreased the risk of death compared with ACEI/ARB, whereas it increased the risk of hypotension for patients with heart failure and decreased the risk of discontinuation due to AEs in White patients. It also increased the risk of dizziness in Asians and decreased the risk of hyperkalemia and renal dysfunction, whereas it increased the risk of hypotension when the study duration was ≥48 weeks. The available evidence showed that sacubitril/valsartan was associated with fewer side effects than ACEI/ARB, except for hypotension. Study duration, race, and patients with primary diseases affected the AEs of sacubitril/valsartan.

Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase.

OBJECTIVE: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. METHODS: A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. RESULTS: Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. CONCLUSION: Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

Combination of inductive effect of lipopolysaccharide and in situ mechanical conditioning for forming an autologous vascular graft in vivo.

Autologous vascular grafts have the advantages of better biocompatibility and prognosis. However, previous studies that implanted bare polymer tubes in animals to grow autologous tubular tissues were limited by their poor yield rates and stability. To enhance the yield rate of the tubular tissue, we employed a design with the addition of overlaid autologous whole blood scaffold containing lipopolysaccharides (LPS). Furthermore, we applied in vivo dynamic mechanical stimuli through cyclically inflatable silicone tube to improve the mechanical properties of the harvested tissues. The effectiveness of the modification was examined by implanting the tubes in the peritoneal cavity of rats. A group without mechanical stimuli served as the controls. After 24 days of culture including 16 days of cyclic mechanical stimuli, we harvested the tubular tissue forming on the silicone tube for analysis or further autologous interposition vascular grafting. In comparison with those without cyclic dynamic stimuli, tubular tissues with this treatment during in vivo culture had stronger mechanical properties, better smooth muscle differentiation, and more collagen and elastin expression by the end of incubation period in the peritoneal cavity. The grafts remained patent after 4 months of implantation and showed the presence of endothelial and smooth muscle cells. This model shows a new prospect for vascular tissue engineering.

[Therapeutic effects of titanium elastic nails for the treatment of clavicular fractures in elder children].

OBJECTIVE: To research the application and clinical effect of titanium elastic nails (TEN) for the treatment of closed clavicular fracture in elder children. METHODS: From October 2010 to December 2012,16 elderly children with clavicular fracture of elder children were treated with internal fixation, including 9 boys and 7 girls with an average age of 14.2 yeats old ranging from 9 to 17 years. The mean time between injury and surgery was 2 to 6 days. Thirteen patients had a transverse fractures; 3 patients had a oblique fractures, excluding the long-oblique patients. Neer function score after 3 months follow-up and the shoulder activity degree after 3 weeks followed were compared respectively between the injured side and healthy side. Fracture reduction and healing were followed up by X-rays to analyze internal fixation with TEN technique. RESULTS: All patients were healed well after surgery. There were 2 cases with soft tissue irritation. No cases of infection, TEN broken, delayed healing or skin bursting were observed. All patients were followed up for 3 to 10 months,with an average of 7.2 months. There were no significant differences (t=2.12, P>0.05) between the healthy side (98.75±2.70) and injured side(96.69±6.22)of Neer score at 3 months during followed up. The shoulder activity at 3 weeks during followed up was different between both sides (P<0.05). The intramedullary nail was removed after X-rays at 12-18 weeks during followed up showed good bone healing,and the shoulder function was recovered well. CONCLUSION: Internal fixation with TEN for the treatment of clavicular fracture has advantages of a limited invasion, beauty, safety and reliability. This technique provides an ideal fixation option for the treatment of clavicular fracture in elder children.

Varicose veins in hairdressers and associated risk factors: a cross-sectional study.

BACKGROUND: Varicose veins (VV) cause not only cosmetic problems but also clinical symptoms such as pain of the affected limbs. Whereas an occupation associated with orthostasis has been recognized as a risk factor of VV, epidemiological studies on working populations are limited. We conducted a study to identify the risk factors of lower limb VV among hairdressers in Taiwan and evaluate their effects, with a focus on long-term standing at work. METHODS: We recruited participants from members of a hairdressers union in southern Taiwan and conducted a questionnaire survey. Data on demographic characteristics, body weight and height, work history, medical history, and other potential related factors were collected from each participant. RESULTS: A total of 182 hairdressers participated in the survey, and 44 (24.2%) had lower limb VV. Uni-variate analyses showed that hairdressers with lower limb VV tended to be older (49.3 vs. 44.7 years, p = 0.032), have a family history of VV (25.6% vs. 9.9%, p = 0.011), doing housework in standing position (86.4% vs. 71.0% , p = 0.042), have a longer work history (30.5 vs. 24.0 years, p = 0.005), and stand longer at work (213.9 vs. 176.0 hour/month, p = 0.008). In multivariate analysis, in hairdressers ≤ 45 years old, the only significant risk factor was a family history of VV (odds ratio [OR] = 11.9, 95% confidence interval [95% CI] = 1.1-133.5). In hairdressers > 45 years old, the risk factors included standing working for > 260 hours per month (OR = 31.8, 95% CI = 1.8-566.5) and working as a hairdresser for > 30 years (for 31-42 years, OR = 10.9, 95% CI = 1.6-73.8; for ≥ 43 years, OR = 12.0, 95% CI = 1.6-88.5). CONCLUSIONS: In hairdressers ≤ 45 years old, family history of VV is a major risk factor for developing lower limb VV, while in those who are > 45 years old, the effects of occupational risk factors are more prominent.