Nur77-IRF1 axis inhibits esophageal squamous cell carcinoma growth and improves anti-PD-1 treatment efficacy.

The nuclear receptor Nur77 plays paradoxical roles in numerous cancers. However, whether Nur77 inhibits esophageal squamous cell carcinoma (ESCC) growth and affects immunological responses against ESCC has not been determined. The functional role of Nur77 in ESCC was investigated in this study using human ESCC cell lines, quantitative real-time polymerase chain reaction (PCR), cell proliferation and colony formation assays, flow cytometry analysis, western blotting and animal models. The target gene controlled by Nur77 was verified using dual-luciferase reporter assays, chromatin immunoprecipitation analysis and functional rescue experiments. To examine the clinical importance of Nur77, 72 human primary ESCC tissues were subjected to immunohistochemistry. Taken together, these findings showed that, both in vitro and in vivo, Nur77 dramatically reduced ESCC cell growth and triggered apoptosis. Nur77 directly interacts with the interferon regulatory factor 1 (IRF1) promoter to inhibit its activity in ESCC. Pharmacological induction of Nur77 using cytosporone B (CsnB) inhibited ESCC cell proliferation and promoted apoptosis both in vitro and in vivo. Furthermore, CsnB increased CD8+ T-cell infiltration and cytotoxicity to inhibit the formation of ESCC tumors in an immunocompetent mouse model. In ESCC tissues, Nur77 expression was downregulated, and IRF1 expression was increased; moreover, their expression levels were negatively related. IRF1 and Nur77 were strongly correlated with overall survival. These findings suggested that Nur77 targets and regulates the IRF1/PD-L1 axis to serve as a tumor suppressor in ESCC. Graphical abstract of the regulatory mechanism of Nur77 overexpression downregulates IRF1 in the inhibition of ESCC progression and enhance anti-PD-1 therapy efficacy.

Inhibition of autophagy-related protein 7 enhances anti-tumor immune response and improves efficacy of immune checkpoint blockade in microsatellite instability colorectal cancer.

BACKGROUND: The efficacy of anti-PD-1 therapy is primarily hindered by the limited T-cell immune response rate and immune evasion capacity of tumor cells. Autophagy-related protein 7 (ATG7) plays an important role in autophagy and it has been linked to cancer. However, the role of ATG7 in the effect of immune checkpoint blockade (ICB) treatment on high microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) CRC is still poorly understood. METHODS: In this study, patients from the cancer genome altas (TCGA) COAD/READ cohorts were used to investigate the biological mechanism driving ATG7 development. Several assays were conducted including the colony formation, cell viability, qRT-PCR, western blot, immunofluorescence, flow cytometry, ELISA, immunohistochemistry staining and in vivo tumorigenicity tests. RESULTS: We found that ATG7 plays a crucial role in MSI-H CRC. Its knockdown decreased tumor growth and caused an infiltration of CD8+ T effector cells in vivo. ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Meanwhile, ATG7 inhibition also suppressed cholesterol accumulation and augmentation of anti-tumor immune responses. Combining ATG7 inhibition and statins improved the therapeutic benefit of anti-PD-1 in MSI-H CRC. Importantly, CRC patients with high expression of both ATG7 and recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) experienced worse prognosis compared to those with low ATG7 and HMGCR expression. CONCLUSIONS: Inhibition of ATG7 leads to upregulation of MHC-I expression, augments immune response and suppresses cholesterol accumulation. These findings demonstrate that ATG7 inhibition has therapeutic potential and application of statins can increase the sensitivity to immune checkpoint inhibitors.

Single Mini-incisional Blepharoplasty with the Orbicularis-Orbital Septum Fixation Technique for the Creation of a Natural Double Eyelid.

BACKGROUND: Mini-incisional double-eyelid blepharoplasty has increasingly gained popularity in oriental populations. Moreover, many related studies have made a detailed technical introduction to this topic. This study aims to introduce a simple single mini-incisional blepharoplasty procedure with orbicularis-orbital septum fixation technique to create a physiologically natural double eyelid with no visible scar and a short postoperative recovery time. METHODS: A single mini-incisional blepharoplasty with orbicularis-orbital septum fixation technique is described in detail and is illustrated with pictures. Patients who underwent this procedure in our department from November 2020 to May 2023 were retrospectively reviewed RESULTS: This study included 159 patients who underwent a single mini-incisional blepharoplasty with the orbicularis-orbital septum fixation technique. Surgery duration ranged from 16 to 42 minutes (mean 27 minutes). The majority of the swelling was reduced in 5 days and completely disappeared in 2 weeks for most patients. The follow-up period ranged from 2 to 31 months. All the double eyelids were natural and dynamic, and the creases were stable with no visible scar. Asymmetries occurred in 1.2% (2 of 159), and crease disappeared in 0.6% (1 of 159) of patients; during the follow-up period, no other complications were reported. Of the 159 patients, 99.4% (158) were satisfied with the surgical outcomes CONCLUSIONS: The single mini-incisional blepharoplasty with the orbicularis-orbital septum fixation technique offers a simple, safe, and effective approach to creating double eyelids. It provides natural, stable, scarless, and rapid recovery results with a low risk of complication. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical outcomes and medical resource utilization of toripalimab combination therapy versus bevacizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer.

OBJECTIVE: This study aimed to evaluate the real-world clinical efficacy and safety, economic burdens and medical resource utilization (MRU) of toripalimab treatment patterns compared with bevacizumab plus chemotherapy (BCP) for patients with advanced non-squamous NSCLC in China. METHODS: Progression-free survival (PFS), adverse drug reactions (ADR) and the costs of drugs, laboratory testing, imageology examinations (including CT, B ultrasound, MRI), medical service, nursing, treatment, genetic test and medical disposable material were compared between two groups. A retrospective observational study was conducted with electronic medical records from Fudan University Huashan hospital. Data was obtained from established electronic medical records (EMRs) and patient surveys. Survival time from the study enrollment to disease progression or death plus from 1st progression disease (PD) in the maintenance phase to 2nd PD (PFS II), adverse events (AE), direct medical costs, MRU and AE-related costs were collected and compared between toripalimab group and BCP group. A total of 246 patients were enrolled. RESULTS: Toripalimab combination therapy has significantly prolonged PFS comparing with BCP (13.8 months vs. 6.2 months, p < .001). A statistically significant improvement in PFS was observed favoring all toripalimab regimen subgroups compared with the bevacizumab group. Patients in toripalimab group occupied more overall resource consumption, more direct medical costs ($47,056.9 vs. $29,951.0, p < .0001) and AE-related costs ($4,500.2 vs. $784.4, p < .0001) than BCP group. Although patients in the toripalimab group used more drugs to prevent AEs ($4,500.2 vs. $784.4, p < .0001), they still experienced more AEs than patients in BCP group (51.4% vs. 41.4%). CONCLUSION: Toripalimab combination therapy could significantly prolonged PFS for patients with advanced non-squamous NSCLC compared with BCP, but at the expense of more MRU, costs and AEs.

STAT3 and STAT6 polymorphisms predict the severity of adverse reactions in Chinese NSCLC patients receiving EGFR-TKIs therapy.

A total of 162 non-small cell lung cancer (NSCLC) patients were divided into discovery (N = 68) and validation (N = 94) groups. Nine Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathway-related single nucleotide polymorphisms were selected to explore the potential associations between genetic polymorphisms and adverse drug reactions (ADRs). The TT genotype of STAT6 rs324011 was significantly associated with severe ADRs in the recessive genetic model (TT vs. CC + CT, OR = 13.5, 95% CI = 2.12-86.09, p = 0.006 in the discovery group; OR = 8.41, 95% CI = 1.95-36.19, p = 0.004 in the validation group). The T allele was associated with a higher incidence of severe ADRs than was the C allele of rs324011 (OR = 3.67, 95% CI = 1.46-9.19, p = 0.006 in the discovery group; OR = 3.17, 95% CI = 1.44-6.99, p = 0.004 in the validation group). Patients with the CC genotype in STAT3 rs1053023 (and rs1053005) or the TT genotype of STAT6 rs324011 were likely to experience severe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) related ADRs.

Carfilzomib suppressed LDHA-mediated metabolic reprogramming by targeting ATF3 in esophageal squamous cell carcinoma.

Carfilzomib, a second-generation proteasome inhibitor, has been approved as a treatment for relapsed and/or refractory multiple myeloma. Nevertheless, the molecular mechanism by which Carfilzomib inhibits esophageal squamous cell carcinoma (ESCC) progression largely remains to be determined. In the present study, we found that Carfilzomib demonstrated potent anti-tumor activity against esophageal squamous cell carcinoma both in vitro and in vivo. Mechanistically, carfilzomib triggers mitochondrial apoptosis and reprograms cellular metabolism in ESCC cells. Moreover, it has been identified that activating transcription factor 3 (ATF3) plays a crucial cellular target role in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively antagonized the effects of carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, the ATF3 protein is specifically bound to lactate dehydrogenase A (LDHA) to effectively suppress LDHA-mediated metabolic reprogramming in response to carfilzomib treatment. Research conducted in xenograft models demonstrates that ATF3 mediates the anti-tumor activity of Carfilzomib. The examination of human esophageal squamous cell carcinoma indicated that ATF3 and LDHA have the potential to function as innovative targets for therapeutic intervention in the treatment of ESCC. Our findings demonstrate the novel function of Carfilzomib in modulating ESCC metabolism and progression, highlighting the potential of Carfilzomib as a promising therapeutic agent for the treatment of ESCC.

Dihydroartemisinin suppresses glioma growth by repressing ERRα-mediated mitochondrial biogenesis.

Malignant gliomas are an exceptionally lethal form of cancer with limited treatment options. Dihydroartemisinin (DHA), a sesquiterpene lactone antimalarial compound, has demonstrated therapeutic effects in various solid tumors. In our study, we aimed to investigate the mechanisms underlying the anticancer effects of DHA in gliomas. To explore the therapeutic and molecular mechanisms of DHA, we employed various assays, including cell viability, flow cytometry, mitochondrial membrane potential, glucose uptake and glioma xenograft models. Our data demonstrated that DHA significantly inhibited glioma cell proliferation in both temozolomide-resistant cells and glioma stem-like cells. We found that DHA-induced apoptosis occurred via the mitochondria-mediated pathway by initiating mitochondrial dysfunction before promoting apoptosis. Moreover, we discovered that DHA treatment substantially reduced the expression of the mitochondrial biogenesis-related gene, ERRα, in glioma cells. And the ERRα pathway is a critical target in treating glioma with DHA. Our results also demonstrated that the combination of DHA and temozolomide synergistically inhibited the proliferation of glioma cells. In vivo, DHA treatment remarkably extended survival time in mice bearing orthotopic glioblastoma xenografts. Thus, our findings suggest that DHA has a novel role in modulating cancer cell metabolism and suppressing glioma progression by activating the ERRα-regulated mitochondrial apoptosis pathway.

ESRRG-PKM2 axis reprograms metabolism to suppress esophageal squamous carcinoma progression and enhance anti-PD-1 therapy efficacy.

BACKGROUND: Glycolysis under normoxic conditions, known as the Warburg effect, confers a selective advantage for the survival and proliferation of many tumors. In this study, we investigated the role of estrogen-related receptor gamma (ESRRG) in metabolic reprogramming in esophageal squamous cell carcinoma (ESCC). METHODS: Bioinformatics analysis indicated that ESRRG expression was decreased in ESCC tissue and associated with poor clinical outcomes. We also examined the effects of altered ESRRG expression on the proliferation and metabolic reprogramming of ESCC cells. We explored the impact of ESRRG on Pyruvate kinase M2 (PKM2) expression and malignant behavior in ESCC. RESULTS: Our study revealed the inhibitory effects of ESRRG on the growth, tumorigenesis, and glycolysis activity of ESCC cells, which were mediated by the downregulation of PKM2 expression. We further demonstrated that ESRRG directly interacts with the PKM2 promoter to inhibit its activity in ESCC. Notably, the ESRRG-specific agonist, DY131, inhibited ESCC cell proliferation and glycolysis activity by modulating genes in the glycolysis pathway. Moreover, we verified that DY131 exhibits enhanced activity as an immune checkpoint inhibitor, considering the significance of the ESRRG-PKM2 axis in the lactate regulation of ESCC cells. CONCLUSION: Our findings provide novel insights into the role of ESRRG-PKM2 signaling in regulating ESCC cell metabolism and immune checkpoint regulation. Additionally, we suggest that DY131 holds promise as a promising therapeutic agent for ESCC treatment.

Exploration on the development of public hospital-sponsored telemedicine platform: A case study in China.

BACKGROUND: As a result of recent advancements, Internet hospitals have been a typic kind of telemedicine platform in China. The platforms can now provide a wide range of medical services while breaking through the limitations of time and space with excellent accessibility. OBJECTIVE: This study aims to give a comprehensive description on the role extension of a public hospital-sponsored Internet hospital in China from the aspects of the characteristics, patient's benefit and satisfaction, the workload of pharmacists and pharmaceutical care. METHODS: The total number of online prescriptions and detailed information were obtained automatically from the Internet hospital information system from Huashan Hospital Fudan University. Age, sex, associated prescription departments, time of prescription, payment methods, expenditure, drug category and delivery region were included in the analysis. A follow-up questionnaire was distributed as an electronic form that was collected and analyzed through the Internet to evaluate patients' satisfaction and time/economic benefits. RESULTS: A total of 51,777 patients visited Internet hospital and purchased required drugs from May 2020 to March 2022. The top 5 online prescription departments were dermatology (83.11%), neurology (6.85%), infectious diseases (3.27%), gastroenterology (2.35%) and cardiology (2.03%) departments. During this period, the audit pharmacists reviewed an average of 240 prescriptions per day, and the consultant pharmacists replied to about 42 consultations per day. 77.89% patients living in westsourth China benefited most from the Internet hospitals. They saved longest time (5 days) and the most expenses ($450-600). We observed an average patient satisfaction score higher than 4.5 in majority dimensions, including drug accessibility, effective in communication and confidence in medical staff. During closed-off management period between April to May in 2022, a total of 194,388 drugs were prescribed and delivered to 19,442 patients with the total payments of $1,547,001.2. Compared with those before closed-off management, the proportion of patients visiting dermatology department reduced from 83.11% to 54.87%. There was a significant increase in the number of patients visited general practice medicine department. The pharmacists extended their working hours by 5 h per day. In 2 months close-off management, the audit pharmacists reviewed an average of 320 prescriptions per day, and the consultant pharmacists replied to about 138 consultations per day. CONCLUSIONS: The characteristics of patients in terms of department and disease profiles in the Internet hospital were consistent with those preponderant disciplines in the entity hospital. Patients benefited from the Internet hospital not only in saving times, but also in reducing medical expenses. During the close-off management period, the distribution of departments and disease profiles changed dramatically. These changes indicated that the Internet hospital was no longer just an extension of in-hospital services, but played an important role in fighting the epidemic, changed the mode of patients' medical treatment and hospital diagnosis and treatment at special times.

VEGF single nucleotide polymorphisms predict improved outcome in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.

We aimed to investigate the prognostic role of genetic variants of VEGF in advanced NSCLC patients treated with platinum-based chemotherapy. A total of 196 patients with advanced NSCLC treated with first-line platinum-based chemotherapy were enrolled. We evaluated the relationship between VEGF polymorphisms and efficacy outcomes and chemotherapy toxicity. We found that rs699947, rs833061 and rs1005230 were in full linkage disequilibrium. Patients with CC genotype of rs833061 had a significant longer PFS than TT genotype (CC vs TT, HR = 1.67, 95%CI = 1.01-2.76, P = 0.043). Patients harbouring CC genotype had longer PFS compared with CT genotype (P < 0.001). Moreover, CC genotypes conferred a significantly increased PFS compared to CT and TT genotype in dominant model (CC vs CT + TT, HR = 1.95, 95%CI = 1.23-3.10, P = 0.005). Patients carrying TT genotype of rs833061 had improved both ORR (HR = 0.54, 95%CI = 0.30-0.98, P = 0.041) and DCR (HR = 0.37, 95%CI = 0.20-0.66, P = 0.001) than non-TT patients. Furthermore, no association was found between any rs833061 alleles and adverse events (P = 0.425), but patients carrying rs1570360 AA genotype were more likely to experience grade 3-4 toxicities (P = 0.004) (GG vs AA, HR = 3.16, 95%CI = 1.26-7.94, P = 0.015). In conclusion, the variant homozygote CC of rs833061 exhibited a better prognosis based on association analysis. The present study provides reference for the future study of platinum-based chemotherapy response and toxicity.

Celastrol upregulated ATG7 triggers autophagy via targeting Nur77 in colorectal cancer.

BACKGROUND: Celastrol is a biologically active ingredient extracted from Tripterygium wilfordii that has exerted properties of anti-cancer. We explored the anti-tumor activities of celastrol against colorectal cancer (CRC) and the potential signaling pathways involved in its mechanism in this study. PURPOSE: The main purpose was to investigate the anti-CRC effects of celastrol and its novel potential mechanisms. STUDY DESIGN: HCT-116 and SW480 cell lines were used for in vitro studies, the mouse xenograft model of CRC tumor was performed for in vivo studies. METHODS: The effects of celastrol on colorectal cancer cells in vitro and underlying mechanisms were examined by using western blot analysis, cell proliferation assays, PI and Annexin-V staining assays, immunofluorescence and qRT-PCR assay. CRC xenografts model and IHC-staining were mainly used to evaluate the effects of celastrol in vivo. RESULTS: The results demonstrated that celastrol induced apoptosis and inhibited proliferation in CRC cells. The expression of Nur77 influenced the anti-CRC effects of celastrol, and inhibitory effect of celastrol on CRC cells could be reversed by overexpressing Nur77. Celastrol induced autophagy and the autophagy inhibition enhanced the anti-CRC effects. The ATG7 was up-regulated obviously after celastrol treatment for Nur77 overexpressing CRC cancer cells. Treating mice implanted with CRC cells with celastrol showed that it effectively inhibited tumor growth, which was associated with the down-regulation of Nur77. Levels of Nur77 and ATG7 were correlated with survival in human colorectal cancer. CONCLUSION: Celastrol induced apoptosis and autophagy played an important role in human colorectal cancer, Nur77 was involved in the anti-CRC effect of celastrol and decreased expression of Nur77 induced high expression of ATG7. Celastrol exerted anti-CRC effects by inhibiting Nur77 to induce high expression of ATG7 signaling and Nur77/ATG7 signaling may be a potential pathway for colorectal cancer treatment.

Ixazomib Induces Apoptosis and Suppresses Proliferation in Esophageal Squamous Cell Carcinoma through Activation of the c-Myc/NOXA Pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the major subtypes of esophageal cancer. More than half of the patients with ESCC in the world are in China, and the 5-year survival rate is less than 10%. As a new oral proteasome inhibitor, ixazomib has shown strong therapeutic effect in many solid tumors. In this study, we aimed to investigate the effects of ixazomib on the proliferation inhibition and apoptosis of ESCC cells. We used four human ESCC cell lines, cell viability assay, cell cycle and apoptosis assay, reverse-transcription polymerase chain reaction (RT-PCR), Western blot, immunohistochemistry, and ESCC xenografts model to clarify the roles of the therapeutic effect and mechanism of ixazomib in ESCC. Ixazomib significantly inhibited the proliferation and induced apoptosis in ESCC cells. RT-PCR results showed that the expressions of endoplasmic reticulum stress-related gene phorbol-12-myristate-13-acetate-induced protein 1 (NOXA) and MYC proto-oncogene (c-Myc) significantly increase after treatment with ixazomib in ESCC cells. When we knocked down the NOXA and c-Myc by small interfering RNA, the therapeutic effect of ixazomib markedly decreased, which confirmed that c-Myc/NOXA pathway played a key role in the treatment of ESCC with ixazomib. In vivo, the xenograft ESCC model mice were given 10 mg/kg of ixazomib every other day for 30 days. The results showed that the tumor size in the treatment group was significantly smaller than the control group. These results suggested that ixazomib is known to suppress proliferation and induce apoptosis in ESCC cell lines, and this effect was likely mediated by increased activation of the c-Myc/NOXA signaling pathways. SIGNIFICANCE STATEMENT: Esophageal squamous cell carcinoma (ESCC) is the common worldwide malignant tumor, but conventional chemotherapeutics suffer from a number of limitations. In this study, the results suggested that ixazomib suppresses proliferation and induces apoptosis in ESCC cell lines. Therefore, ixazomib may be a potential new strategy for ESCC therapy.

Embracing Responsible Leadership and Enhancing Organizational Citizenship Behavior for the Environment: A Social Identity Perspective.

Although organizational citizenship behavior for the environment (OCBE) literature has highlighted the critical role of leadership on the emergence of OCBE, there is still room for further research exploration of how and when leaders influence subordinates' OCBE. According to social identity theory, we propose a theoretical model that responsible leadership promotes subordinates' OCBE by examining subordinates' moral identity as a mediator and individualism as a boundary condition. Using a sample of 273 collected in China, results indicated that responsible leadership was positively related to subordinates' moral identity, which in turn was positively related to subordinates' OCBE. Subordinates' moral identity partially mediated the relationship between responsible leadership and their OCBE. In addition, both the relationship between responsible leadership and subordinates' moral identity and the indirect relationship between responsible leadership and subordinates' OCBE were stronger when individualism was lower. These findings provide novel insights into how responsible leadership influences OCBE and how such influence is shaped by subordinates' individualism.

Treatment of Recurrent Axillary Osmidrosis: Trimming and Electrocoagulation of Apocrine Glands Under Direct Vision Through Double Incisions.

OBJECTIVE: The aim of this study was to explore the clinical effect of treatment for recurrent axillary osmidrosis (AO) after small-incision minimally invasive surgery by trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases. METHODS: This was a retrospective study. From September 2012 to January 2019, 75 axillae in 48 cases of recurrent AO after small-incision minimally invasive surgery were treated using trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases. Patient data, such as sex, age, original surgery method, the severity of underarm malodor before and after the operation, and occurrence of complications, were collected and analyzed. RESULTS: For the follow-up of at least 12 months after the surgery, all patients' underarm malodor disappeared or was significantly reduced. Patients with preoperative severity of grade I did not show a recurring AO, whereas the recurrence rate of grade II and grade III AO was 7.9% and 14.3%, respectively. Furthermore, the AO recurrence rate was 9.1% for those younger than 18 years and 6.2% in those 18 years or older. Subcutaneous hematomas appeared on 3 axillae (4.0%), and the contraction of subdermal fibrotic bands appeared on 5 axillae (6.7%). CONCLUSIONS: Patients with recurring AO after small-incision minimally invasive surgery achieved good treatment results by trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases.

Reduced emergency room visits and improved medication adherence of an integrated oncology pharmaceutical care practice in China.

OBJECTIVE: We described our initial experience of a new integrated oncology phamaceutical care practice to enhance the quality of pharmacy service and patient care in Huashan hospital.Data sources: A retrospective study was performed from August 2019 to September 2020. Patients were described as integrated pharmacy service group and routine care group. Medication adherence of patients in integrated pharmacy service group was recorded by the online management system. Patient satisfaction and the cumulative incidence of emergency room (ER) and outpatient visit were evaluated between two groups.Data summary: In total, 323 patients received the integrating oncology pharmacy service. The percentage of the patients missing administration every day was reduced from 29.7% to 0.3% within a 40-day monitoring and intervention period. There was a significant difference on patient satisfaction with pharmacy service in two groups (P < 0.05). Fewer patients in the integrated pharmacy service group visited clinic and ER compared with routine care group (33.1% vs. 59.2%; P < 0.05). CONCLUSIONS: As a new practice model, the integrated program is adopted to provide patient care and ongoing monitoring for cancer patients. The practice model delivers high continuity of care for cancer patients and improves communication and collaboration between healthcare professionals and oncology patients. The practice also provides the potential of developing hospital pharmaceutical service and optimizing disease prevention and treatment strategies.

Rhinoplasty With Hyaluronic Acid: A Standard 5-step Injection Procedure Using Sharp Needle.

OBJECTIVE: To explore the clinical effect of rhinoplasty with a standard 5-step injection procedure of hyaluronic acid using sharp needle in correction of deficient features of the Chinese nose. METHODS: Between January 2016 and December 2018, hyaluronic acid was injected with the sharp needle by a standard procedure in the anterior nasal spine, nasal columella, nasal tip, nasal root, and dorsum, as well as the junction region of nasal root and brow in 198 Chinese patients. The postoperative curative effect was analyzed, and the adverse reactions were observed. RESULTS: The nasal shape in all patients was significantly improved, obtaining the stereoscopic appearance, and satisfactory results. During a 6-month follow-up, 4 patients developed local subcutaneous congestion and bruising in the nasal dorsum after treatment, which disappeared within 2 weeks. No patients suffered from complications such as infection, embolism, necrosis, transparent nasal dorsum, and widened nasal roots. CONCLUSIONS: Injection of hyaluronic acid with the sharp needle by a standard 5-step procedure is a safe technique that can effectively correct the deficient features of the Chinese nose.

Objective and Subjective Evaluation of Lipoinjection for Correction of Temporal Depression.

BACKGROUND: Temporal depression is commonly found among people. OBJECTIVE: Objective and subjective evaluation of lipoinjection for correction of temporal depression. METHODS: From November 2012 to January 2018, 34 healthy female subjects underwent temporal augmentation by lipoinjection on both sides. Efficacy was assessed by objective and subjective parameters. The quantitative measurement of the temporal defect was obtained using molded plasticine preoperatively and 12 months after treatment. The subjective assessment consisted of excellent, good, fair, and poor results based on the patients' self-evaluations. The adverse events were recorded. RESULTS: The follow-up period ranged from 12 to 36 months. It was found that a statistically significant difference existed between the preoperative and postoperative defect on both temples. Regarding the patients' self-evaluations, 17 patients (50.0%) reported feeling excellent, 15 patients (44.1%) as good, and 2 patients (5.9%) as fair, and no patient as poor. After the statistical analysis, it was found that the volumetric restoration rate of the grafted fat decreased as the temporal defect generally increased during the aging process. Injection-site swelling and bruising were commonly found complications; other complications were not found. CONCLUSION: Autologous fat is inexpensive and readily available. Fat grafting is an alternative for correction of temporal depression.

The Increased Expression of Estrogen-Related Receptor α Correlates with Wnt5a and Poor Prognosis in Patients with Glioma.

Malignant glioma is an often fatal type of cancer. Elevated expression of the orphan nuclear receptor estrogen-related receptor alpha (ERRα) is an unfavorable factor for malignant progression and poor prognosis in several cancers, although the mechanism by which this receptor affects the pathophysiology of cancers remains obscure. However, few studies have been conducted in regard to the role of ERRα in glioma. In the current study, we found that elevated expression of ERRα was observed in 107 glioma cases by means of IHC. Clinically, high expression of ERRα was associated with later stages of disease progression and clinical outcome of patients with glioma. ERRα had the ability to promote cell proliferation and migration in glioma cell lines. Moreover, in a xenograft model, we also found that silencing ERRα had an inhibitory effect on the growth of glioma. Further investigation confirmed that ERRα was involved in the carcinogenesis of glioma via the regulation of the Wnt5a signal pathway in vitro and in vivo Our study was first to show the overexpression of ERRα in glioma tissues and a direct correlation between ERRα expression and clinical prognosis of glioma. Together, these data reveal that ERRα has prognostic significance in glioma, and targeting ERRα may provide a reliable therapeutic strategy for the treatment for human glioma.

Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel-based chemotherapy in breast cancer patients.

BACKGROUND: The chemotherapy resistance and toxicity of chemotherapy are major problems in breast cancer treatment. However, candidate biomarkers for predicting clinical outcomes and better prognosis remain lacking. METHODS: In this study, we analyzed possible impact of 8 genetic variants of fibroblast growth factor receptor1-4 (FGFR1-4) on the treatment response and toxicities in 211 breast cancer patients. DNA was extracted from peripheral blood cells, and the genotypes were examined using the TaqMan Pre-Designed SNP Genotyping Assays. RESULTS: The FGFR4 rs1966265 and FGFR2 rs2981578 contributed to clinical outcome of breast cancer treated with docetaxel-epirubicin-cyclophosphamide (CET)-based chemotherapy. For rs1966265, AA genotype had significant correlation with the clinical response to neoadjuvant chemotherapy (NCT) when compared with GG and AG/GG genotype (P = 0.019 and P = 0.004, respectively). Moreover, A allele of FGFR2 rs2981578 had significant rates of response (P = 0.025). In addition, rs2420946 CC genotype was associated with higher frequency of toxicities compared with TT and CT/TT genotypes (P = 0.038 and P = 0.019, respectively). Also, rs2981578 AG genotype showed higher frequency of toxicities compared with GG genotype (P < 0.0001). CONCLUSIONS: The results suggest these polymorphisms, especially rs1966265 and rs2981578, might be candidate pharmacogenomics factors to the response and prognosis prediction for individualized CET-based chemotherapy in breast cancer patients.

Large-area gold nanohole arrays fabricated by one-step method for surface plasmon resonance biochemical sensing.

Surface plasmon resonance (SPR) nanosensors based on metallic nanohole arrays have been widely reported to detect binding interactions in biological specimens. A simple and effective method for constructing nanoscale arrays is essential for the development of SPR nanosensors. In this work, we report a one-step method to fabricate nanohole arrays by thermal nanoimprinting in the matrix of IPS (Intermediate Polymer Stamp). No additional etching process or supporting substrate is required. The preparation process is simple, time-saving and compatible for roll-to-roll process, potentially allowing mass production. Moreover, the nanohole arrays were integrated into detection platform as SPR sensors to investigate different types of biological binding interactions. The results demonstrate that our one-step method can be used to efficiently fabricate large-area and uniform nanohole arrays for biochemical sensing.