A piezoelectric-driven microneedle platform for skin disease therapy.

With over a million cases detected each year, skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate, propensity for recurrence, and potential for post-treatment scarring. Photodynamic therapy (PDT) is a treatment with minimal invasiveness or scarring and few side effects, making it well tolerated by patients. However, this treatment requires further research and development to improve its effective clinical use. Here, a piezoelectric-driven microneedle (PDMN) platform that achieves high efficiency, safety, and non-invasiveness for enhanced PDT is proposed. This platform induces deep tissue cavitation, increasing the level of protoporphyrin IX and significantly enhancing drug penetration. A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT (PDMN-PDT). Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25% and 50%, respectively, without any anesthesia compared to traditional PDT. These findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment, which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

[Application and efficacy analysis of tympanic cartilage shaping device in endoscopic type â tympanoplasty].

Objective:To study the feasibility and efficacy of using a tympanic cartilage shaping device in endoscopic type Ⅰ tympanoplasty. Methods:A tympanic cartilage shaper was designed and manufactured by measuring tympanic membrane dimensions with HRCT imaging for cutting and shaping cartilage to repair the tympanic membrane. From August 2019 to October 2021, 66 patients（72 ears） with chronic suppurative otitis media in Xiangya Hospital underwent endoscopic type Ⅰ tympanoplasty with this tympanic cartilage shaping device, and were observed the tympanic membrane healing and hearing recovery effect after surgery. Postoperative follow-up ranged from 3-24 months, with an average of 9 months. The data were analyzed by the SPSS 26.0 software. Results:According to the imaging measurements, tympanic pars tensa width（8.60±0.20） mm, height（8.64±0.19） mm, design and manufacture a cylindrical cartilage shaping device with inner diameter 8.60 mm. After tympanoplasty, the healing rate of tympanic membrane was 100%; The average air-bone gap before surgery was（23.10±7.33） dB, then（14.30±6.40） dB 1 month after surgery, which were significant reduced compared with those before surgery. The average air-bone gap was（14.30±6.40） dB 3 month after surgery compared with 1 month after surgery, the difference was also statistically significant（t=6.630, P<0.05）. Conclusion:The tympanic membrane cartilage shaper shaping cartilage in endoscopic tympanoplasty is simple, stable and reliable, which can reduce the time of graft cartilage processing, improve the efficiency of surgery, and restore the tympanic membrane morphology and function in the postoperative period.

Low-Frequency Ultrasound Sensitive Piezo1 Channels Regulate Keloid-Related Characteristics of Fibroblasts.

Keloids are benign fibroproliferative tumors that severely diminish the quality of life due to discomfort, dysfunction, and disfigurement. Recently, ultrasound technology as a noninvasive adjuvant therapy is developed to optimize treatment protocols. However, the biophysical mechanisms have not yet been fully elucidated. Here, it is proposed that piezo-type mechanosensitive ion channel component 1 (Piezo1) plays an important role in low-frequency sonophoresis (LFS) induced mechanical transduction pathways that trigger downstream cellular signaling processes. It is demonstrated that patient-derived primary keloid fibroblasts (PKF), NIH 3T3, and HFF-1 cell migration are inhibited, and PKF apoptosis is significantly increased by LFS stimulation. And the effects of LFS is diminished by the application of GsMTx-4, the selective inhibitor of Piezo1, and the knockdown of Piezo1. More importantly, the effects of LFS can be imitated by Yoda1, an agonist of Piezo1 channels. Establishing a patient-derived xenograft keloid implantation mouse model further verified these results, as LFS significantly decreased the volume and weight of the keloids. Moreover, blocking the Piezo1 channel impaired the effectiveness of LFS treatment. These results suggest that LFS inhibits the malignant characteristics of keloids by activating the Piezo1 channel, thus providing a theoretical basis for improving the clinical treatment of keloids.

[Corrigendum] Downregulation of CD147 induces malignant melanoma cell apoptosis via the regulation of IGFBP2 expression.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the ß­actin bands shown for the western blots portrayed in Fig. 4A and E on p. 2403 appeared to be strikingly similar, albeit that the bands were inverted with respect to their orientation and the dimensions of the bands differed slightly. After re­examining their original data, the authors have realized that these data in Fig. 4 had inadvertently been assembled incorrectly. The revised version of Fig. 4, showing the correct data for all the experiments in Fig. 4E, is shown on on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree to its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 53: 2397­2408, 2018; DOI: 10.3892/ijo.2018.4579].

Protocol for fabrication of Pt/RuO2/graphene bifunctional oxygen catalyst in Li-O2 batteries.

The commercial mass production of bifunctional oxygen catalysts with high activity and stability is critical for constructing high-performance lithium-oxygen (Li-O2) batteries, but remains challenging. Herein, we describe a protocol for the scalable fabrication of a 2D bifunctional electrocatalyst of Pt/RuO2/graphene by spatial confinement strategy and elaborately evaluate its oxygen reduction/evolution reactions for advanced Li-O2 batteries. We then detail the synthesis steps for preparing materials followed by assembly and evaluation of the three-electrode systems and coin-type Li-O2 batteries. For complete details on the use and execution of this protocol, please refer to Li et al. (2023).1.

Real-World, Multicenter Case Series of Patients Treated with Isavuconazole for Invasive Fungal Disease in China.

BACKGROUND: The incidence of invasive fungal disease (IFD) has increased significantly, and IFD is a major cause of mortality among those with hematological malignancies. As a novel second-generation triazole antifungal drug offering both efficacy and safety, isavuconazole (ISA) is recommended by various guidelines internationally for the first-line treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) infecting adults. Given that it was only approved in China at the end of 2021, there is currently a lack of statistical data regarding its usage in the Chinese population. The primary objective of this report is to describe early experiences with ISA for the treatment of IFD. METHODS: This was a real-world, multicenter, observational case series study conducted in China. It included patients from three centers who received ISA treatment from January 2022 to April 2023. A retrospective assessment on patient characteristics, variables related to ISA administration, the treatment response of IFD to ISA, and potential adverse events attributed to ISA was conducted. RESULTS: A total of 40 patients met the inclusion criteria. Among them, 12 (30%) were diagnosed with aspergillosis, 2 (5%) were diagnosed with candidiasis, 12 (30%) were diagnosed with mucormycosis, and 14 cases did not present mycological evidence. The predominant site of infection was the lungs (36), followed by the blood stream (8), sinuses (4), and respiratory tract (2). The overall response rate was 75% (30 patients), with male patients having a higher clinical response than female patients (24/24 versus 6/16, p = 0.000) and autologous stem cell transplant patients having a higher clinical response than allogeneic stem cell transplant patients (6/6 versus 4/10, p = 0.027). During the observation period, four patients experienced adverse effects associated with ISA, but none of them discontinued the treatment. CONCLUSIONS: Our findings suggest that ISA, a novel first-line treatment for IA and IM, is associated with a high clinical response rate, low incidence, and a low grade of adverse effects. Given the short time that ISA has been available in China, further research is needed to identify its efficacy and safety in the real world.

Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer.

Although immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from Streptomyces hydrophobicus. We found that nigericin caused cell death in TNBC cell lines MDA-MB-231 and 4T1 by inducing concurrent pyroptosis and apoptosis. As nigericin facilitated cellular potassium efflux, we discovered that it caused mitochondrial dysfunction, leading to mitochondrial ROS production, as well as activation of Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis in TNBC cells. Notably, nigericin-induced pyroptosis could amplify the anti-tumor immune response by enhancing the infiltration and anti-tumor effect of CD4+ and CD8+ T cells. Moreover, nigericin showed a synergistic therapeutic effect when combined with anti-PD-1 antibody in TNBC treatment. Our study reveals that nigericin may be a promising anti-tumor agent, especially in combination with immune checkpoint inhibitors for advanced TNBC treatment.

Clinical characteristics and surgical strategy of glomus tympanicum tumors. / 鼓室体瘤的临床特征及手术策略.

OBJECTIVES: To summarize the clinical characteristics of glomus tympanicum tumors, and to explore the surgical methods and the strategy for auditory protection. METHODS: Ten cases (ears) of glomus tympanicum tumors were collected from the Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University from August 2014 to February 2022. All patients underwent endoscopic or microscopic surgery to achieve total removal of the tumor, followed up for 3 months to 8 years. We summarized and analyzed its clinical characteristics, compared the preoperative and postoperative hearing levels of patients, and made a retrospective summary of the surgical methods and the strategy for auditory protection. RESULTS: Ten patients were all female at (49.50±8.00) years old. Their medical history ranged from 15 days to 6 years. Seven patients complained of pulsatile tinnitus, and 80% (8/10) of the affected ears suffered different degrees of hearing loss. According to the modified Fisch & Mattox classification of glomus tympanicum tumors, 3 ears (30%) of 10 ears were A1, 2 ears (20%) were A2 and 5 ears (50%) were B1. In all 10 cases (ears), hearing was improved in 3 cases, bone gas conductance was maintained in 6 cases, and hearing was slightly decreased in 1 case. The difference of bone gas conductance was 0-10 dB in 7 cases (ears) after operation, and 10-20 dB in 3 cases (ears). There was no significant difference in the average air conduction hearing threshold, bone conduction hearing threshold and air-bone conduction difference between before and after operation (all P>0.05). All cases had no postoperative complications, and the external auditory canal and the incision behind the ear healed well. There was no recurrence after follow-up. CONCLUSIONS: Glomus tympanicum tumor is easy to bleed, so it is a challenge for total tumor resection and hearing function protection during operation. For type A and type B1 tumors, they can be completely removed under the condition of keeping the tympanic membrane and the ossicular chain. At the same time, the postoperative hearing function can be preserved, and even the hearing can be improved.

Photodynamic therapy combined with surgery versus Mohs micrographic surgery for the treatment of difficult-to-treat basal cell carcinoma: a retrospective clinical study.

BACKGROUND: Mohs micrographic surgery (MMS) is the preferable surgery for difficult -to-treat basal cell carcinoma (BCC) but is an expensive, labor-intensive, and time-consuming technique. The aim of this study is to compare the efficacy and safety of photodynamic therapy combined with surgery(S-PDT) versus Mohs micrographic surgery (MMS) for the treatment of difficult-to-treat BCC. METHODS: This was a retrospective, comparative study. A total of 32 patients, 16 patients with 48 lesions, were treated with S-PDT, and the other 16 patients with 17 lesions treated by MMS were enrolled in this study. Follow-up was at least 36 months posttreatment. RESULTS: The recurrence rate was no statistical difference between the S-PDT and MMS (p = 1.000, Fishers exact test). The median follow-up was 42.5 months (range 36-63 months). The mean healing time in the S-PDT [17.9 d (SD 9.8)] is longer than in MMS [7.5 d (SD 1.5)] during follow-up (p＜.001, Independent T-test). On the whole, the cosmetic outcome of patients in S-PDT was statistically no significant difference with that in MMS according to a 4-point scale (p = .719, chi-squared test). CONCLUSIONS: S-PDT is a safe, effective, and novel cosmetic treatment, which holds the potential to be an alternative treatment to MMS for some cases.

[Analysis of therapeutic effect of tympanoplasty type â in elderly patients with chronic suppurative otitis media].

Objective:To summarize the clinical characteristics of elderly patients with chronic suppurative otitis media who underwent type Ⅰ tympanoplasty, and to analyze for the first time the efficacy of type Ⅰtympanoplasty in elderly patients from multiple perspectives of medical data and patient evaluation, so as to provide reference for doctors and patients to make rational decisions on treatment methods. Methods:Forty-four elderly patients（45 ears） who underwent type Ⅰtympanoplasty from May 2016 to February 2022 were retrospectively analyzed, and were followed up for 6 months to 3 years. To analyze the clinical characteristics of patients, summarize the success rate of graft, and compare the hearing level of patients before and after surgery. The patients' quality of life before and after operation was evaluated by Chronic Ear Survey, and the scores obtained were statistically analyzed. Results:Of the 44 patients（45 ears）, 22.22%（10/45） of the ears had predisposing factors. The percentage of hearing loss, ear pus and tinnitus were 91.11%（41/45）, 88.89%（40/45） and 42.22%（19/45）, respectively. Mixed deafness accounted for 55.56%（25/45）. 66.67%（30/45） patients were diagnosed as tympanosclerosis by operation. The graft success rate was 97.78%. There was no significant difference in bone conduction hearing threshold before and after surgery, but there was significant difference in air conduction hearing threshold and air bone conduction difference. The scores of "activity restriction", "symptom", "medical resource utilization" and their total scores of the preoperative and postoperative were statistically different. Hypertension or diabetes had no significant effect on the efficacy of type Ⅰ tympanoplasty in elderly patients. Conclusion:Type Ⅰtympanoplasty is safe and effective in elderly patients, and the quality of life of patients after surgery is significantly improved. It is necessary to increase the awareness of elderly patients to seek medical advice and use surgical methods reasonably to treat chronic suppurative otitis media.

Frizzled-7-targeting antibody (SHH002-hu1) potently suppresses non-small-cell lung cancer via Wnt/ß-catenin signaling.

Non-small-cell lung cancer (NSCLC) is one of the deadliest cancers worldwide, and metastasis is considered one of the leading causes of treatment failure in NSCLC. Wnt/ß-catenin signaling is crucially involved in epithelial-mesenchymal transition (EMT), a crucial factor in promoting metastasis, and also contributes to resistance developed by NSCLC to targeted agents. Frizzled-7 (Fzd7), a critical receptor of Wnt/ß-catenin signaling, is aberrantly expressed in NSCLC and has been confirmed to be positively correlated with poor clinical outcomes. SHH002-hu1, a humanized antibody targeting Fzd7, was previously successfully generated by our group. Here, we studied the anti-tumor effects of SHH002-hu1 against NSCLC and revealed the underlying mechanism. First, immunofluorescence (IF) and near-infrared (NIR) imaging assays showed that SHH002-hu1 specifically binds Fzd7+ NSCLC cells and targets NSCLC tissues. Wound healing and transwell invasion assays indicated that SHH002-hu1 significantly inhibits the migration and invasion of NSCLC cells. Subsequently, TOP-FLASH/FOP-FLASH luciferase reporter, IF, and western blot assays validated that SHH002-hu1 effectively suppresses the activation of Wnt/ß-catenin signaling, and further attenuates the EMT of NSCLC cells. Finally, the subcutaneous xenotransplanted tumor model of A549/H1975, as well as the popliteal lymph node (LN) metastasis model, was established, and SHH002-hu1 was demonstrated to inhibit the growth of NSCLC xenografts and suppress LN metastasis of NSCLC. Above all, SHH002-hu1 with selectivity toward Fzd7+ NSCLC and the potential of inhibiting invasion and metastasis of NSCLC via disrupting Wnt/ß-catenin signaling, is indicated as a good candidate for the targeted therapy of NSCLC.

Removal of chromium from water using manganese (II, III) oxides coated sand: adsorption and transformation of Cr(VI) and Cr(III).

A manganese coated sand (MCS) sorbent containing manganese (II,III) oxides was developed for adsorption and transformation of chromium [Cr(VI) and Cr(III)] with potential application in flow-through permeable media adsorption filters. Characterization of the MCS sorbent using XRD and XPS showed that the oxides of manganese (II) and manganese (III) were present on the MCS sorbent surface. Adsorption of both Cr(VI) and Cr(III) onto the MCS sorbent occurred over a broad pH range from 3 to 10. Surface charge analysis of the MCS sorbent determined a pHPZC of 7.8, which may facilitate the uptake of both oxy-anionic Cr(VI) species and cationic Cr(III) species. Favorable adsorption of Cr(VI) and Cr(III) onto the MCS sorbent occurred according to the Langmuir and the Freundlich adsorption equations, with a higher adsorption capacity for Cr(III) than Cr(VI). Adsorption parameters from the Langmuir, the Freundlich and the Temkin adsorption equations showed a stronger binding of Cr(VI) than Cr(III). Adsorption of Cr(III) decreased with increasing calcium concentration while adsorption of Cr(VI) decreased with increasing concentration of common anions found in natural water in the following order: phosphate > sulfate> bicarbonate. Transformation of chromium occurred on the surface of the MCS sorbent due to the partial reduction of Cr(VI) and the partial oxidation of Cr(III), which may be attributed to the role of surface manganese (II,III) oxides as either reducing or oxidizing agents. The MCS sorbent is a recyclable and sustainable adsorbent for removal of chromium from water with an environmental impact comparable to ion-exchange technology.

Apigenin Induced Apoptosis by Downregulating Sulfiredoxin Expression in Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second carcinoma in nonmelanoma skin cancer (NMSC). Sulfiredoxin (Srx) is an antioxidant protein with a role in maintaining redox homeostasis. And Srx has an oncogenic role in skin tumorigenesis. In the current study, we found that apigenin, as a natural flavonoid, downregulated the expression of Srx protein in cSCC cell lines. Apigenin also inhibited the ability of cell proliferation and migration and induced apoptosis in cSCC cell lines. Our results also showed that apigenin induced apoptosis via the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, as well as downregulated Srx expression in cSCC cell lines. Importantly, the effect of downregulation Srx by apigenin has been rescued with the inhibitor of the MAPK signaling pathway intervention. And induced apoptosis by apigenin was partially attenuated by the addition of MAPK inhibitor, Binimetinib. Our research revealed that apigenin induced apoptosis by downregulation of Srx expression through regulating the MAPK signaling pathway in cSCC cells, thus providing evidence of its applicability as a potentially effective therapeutic agent for cSCC treatment.

DNA Repair Protein HELQ and XAB2 as Chemoresponse and Prognosis Biomarkers in Ascites Tumor Cells of High-Grade Serous Ovarian Cancer.

Nucleotide excision repair (NER) is an important mediator for responsiveness of platinum-based chemotherapy. Our study is aimed at investigating the NER-related genes expression in ascites tumor cells and its application in the prediction of chemoresponse in high-grade serous ovarian cancer (HGSC) patients. The relationship between 16 NER-related genes and the prognosis of ovarian cancer was analyzed in the TCGA database. NER-related genes including HELQ and XAB2 expressions were determined via immunocytochemistry in ascites cell samples from 92 ovarian cancer patients prior to primary cytoreduction surgery. Kaplan-Meier analysis and Cox model were used to investigate the association between NER-related gene expression and prognosis/chemotherapeutic response. Predicting models were constructed using a training cohort of 60 patients and validated in a validation cohort of 32 patients. We found that high expression of HELQ and XAB2 in the training cohort was associated with poor prognosis (for HELQ, P = 0.001, HR = 2.83, 95% CI: 1.46-5.49; for XAB2, P = 0.008, HR = 2.38, 95% CI: 1.23-4.63) and platinum resistance (for HELQ, P < 0.001; for XAB2, P = 0.006). In the validation cohort, the combination of HELQ and XAB2 (AUC = 0.863) showed the highest AUC. The expression levels of HELQ (RR 5.7, 95% CI 1.7-19.2) and XAB2 (RR 3.2, 95% CI 0.9-10.8) in ascites tumor cells were positively correlated to the risk of platinum resistance. In summary, we revealed that the expression levels of HELQ and XAB2 are candidate predictors for primary chemotherapy responsiveness and prognosis in HGSC. Ascites cytology is applicable as a promising method for chemosensitivity prediction in HGSC.

Establishment of a risk index for early complications after trans-canal endoscopic ear surgery.

PURPOSE: This study aimed to determine the risk factors associated with early postoperative complications of trans-canal endoscopic ear surgery (TEES), then to develop a risk index. MATERIALS AND METHODS: This single-institution retrospective study reviewed TEESs from January 1, 2017, to December 31, 2019 in a tertiary hospital. In the derivation cohort, univariable and multivariable logistic regression were performed to identify factors significantly associated with early postoperative complications of TEES. Then these parameters were integrated into a trans-canal endoscopic ear surgery risk index (TEESRI). The performance of TEESRI was compared with that of the American Society of Anesthesiologists (ASA) classification using the validation cohort. RESULTS: 932 TEESs were enrolled in total and 151 (16.2%) developed early postoperative complications. In the derivation set, 8 factors including state of the opposite ear and presence of nasal or pharyngeal diseases were found to be independently associated with the occurrence of early postoperative complications on multivariable regression analysis [area under the curve (AUC), 0.806; 95% confidence interval (CI), 0.765-0.848]. Using the validation cohort, the AUC of the TEESRI was 0.776 [95%CI, 0.711-0.842], with a sensitivity of 82.2% and specificity of 65.5%, while the AUC of the ASA classification was 0.512 (95%CI, 0.421-0.603). The TEESRI outperformed the ASA classification when evaluating the risk for early postoperative complications of TEES. CONCLUSIONS: Based on the 8 risk factors, the TEESRI was established with satisfactory predicting capacity. Surgeons should pay extra attention to the risk factors in the TEESRI, when treating patients.

Triage by PAX1 and ZNF582 Methylation in Women With Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Case-Control Study.

Background: The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance. Methods: This was a multicenter study and included 277 histologically confirmed CIN3 women who underwent cold knife conization (CKC) from January 2019 to December 2020. The methylation levels of PAX1 (PAX1m) and ZNF582 (ZNF582m) were determined by quantitative methylation-specific polymerase chain reaction (qMSP) and expressed in ΔCp. Receiver operating characteristic curves were used to evaluate predictive accuracy. Results: The final pathological results in 48 (17.33%) patients were inflammation or low-grade squamous intraepithelial lesion (LSIL), 190 (68.59%) were high-grade squamous intraepithelial lesion (HSIL), and 39 (14.08%) were squamous cervical cancer (SCC). PAX1m and ZNF582m increased as lesions progressed from inflammation/LSIL, HSIL, to SCC. PAX1 and ZNF582 methylation yielded better prediction performance compared with common screening strategies, whether individually or combined. A 4.33-fold increase in the probability of inflammation/LSIL was observed in patients with lower ZNF582 methylation levels (ΔCpZNF582 ≥ 19.18). A 6.53-fold increase in SCC risk was observed in patients with elevated ZNF582 methylation (ΔCpZNF582 < 7.09). Conclusions: DNA methylation would be an alternative screening method to triage and predict the final outcome of conization in CIN3 cases.