Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Paclitaxel liposome, cisplatin and 5-fluorouracil-based induction chemotherapy followed by de-escalated intensity-modulated radiotherapy with concurrent cisplatin in stage IVA-IVB childhood nasopharyngeal carcinoma in endemic area: a phase II, single-arm trial.

Background: Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation. Methods: We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60 Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70 Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT). Findings: From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65-90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82-99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation. Interpretation: Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Effect of beinaglutide treatment on weight loss in Chinese patients with type 2 diabetes mellitus and overweight/obesity

ABSTRACT Objective: To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers. Materials and methods: This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m2 and T2DM. Beinaglutide was administered for three months. Changes in body weight, fasting plasma glucose (FPG) level, 2 h postprandial plasma glucose (2h-PG) level, glycosylated hemoglobin (HbA1c) level, BMI and visceral and subcutaneous fat areas were measured at baseline and after three months of treatment. In addition, relevant inflammation/obesity cytokines and biomarkers were measured. Results: After three months, beinaglutide treatment led to significant changes, including in body weight, BMI, FPG level, HbA1c level, visceral and subcutaneous fat areas. In addition, serpin E1, leptin, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) also decreased significantly. The plasma protein concentrations of CRP (Log2 transformed) were found to be positively correlated with the percentage of weight loss (R = 0.514 and p-value = 0.021). Conclusion: Beinaglutide treatment resulted in weight loss, plasma glucose control and anti-inflammatory effects in patients with T2DM and overweight/obesity.

Effect of beinaglutide treatment on weight loss in Chinese patients with type 2 diabetes mellitus and overweight/obesity.

OBJECTIVE: To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers. METHODS: This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m2 and T2DM. Beinaglutide was administered for three months. Changes in body weight, fasting plasma glucose (FPG) level, 2 h postprandial plasma glucose (2h-PG) level, glycosylated hemoglobin (HbA1c) level, BMI and visceral and subcutaneous fat areas were measured at baseline and after three months of treatment. In addition, relevant inflammation/obesity cytokines and biomarkers were measured. RESULTS: After three months, beinaglutide treatment led to significant changes, including in body weight, BMI, FPG level, HbA1c level, visceral and subcutaneous fat areas. In addition, serpin E1, leptin, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) also decreased significantly. The plasma protein concentrations of CRP (Log2 transformed) were found to be positively correlated with the percentage of weight loss (R = 0.514 and p-value = 0.021). CONCLUSION: Beinaglutide treatment resulted in weight loss, plasma glucose control and anti-inflammatory effects in patients with T2DM and overweight/obesity.

Diversity and communities of culturable endophytic fungi from different tree peonies (geoherbs and non-geoherbs), and their biosynthetic potential analysis.

To know more about the potential roles of endophytic fungi in the formation mechanism of Daodi medicinal material, diversity and communities of culturable endophytic fungi in three types of tree peonies were investigated. Endophytic fungi of three types of tree peonies were isolated and identified. The diversity was analyzed. Bayesian trees constructed by MrBayes 3.2.6 after phylogenetic analysis of the ITS sequences. The endophytic fungi potential for synthesis of natural products was assessed by means of detecting NRPS and PKS gene sequences. In total, 364 endophytic fungi isolates representing 26 genera were recovered from Paeonia ostii 'Feng Dan', Paeonia ostii 'Luoyang Feng Dan', and Paeonia suffruticosa 'Luoyang Hong'. More culturable endophytic fungi appeared in P. suffruticosa 'Luoyang Hong' (206) compared with P. ostii 'Feng Dan' (60) and P. ostii 'Luoyang Feng Dan' (98). The fungal community of P. ostii 'Feng Dan' had the highest richness and diversity. PKSs and NRPS detection rates of endophytic fungi from P. ostii 'Feng Dan' are both the highest among the three types of tree peonies. Results indicate that endophytic fungus is an important factor of Daodi Cortex Moutan forming, and endophytic fungi in peony are related to genuineness of Cortex Moutan.

Diversity and communities of culturable endophytic fungi from different tree peonies (geoherbs and non-geoherbs), and their biosynthetic potential analysis

Abstract To know more about the potential roles of endophytic fungi in the formation mechanism of Daodi medicinal material, diversity and communities of culturable endophytic fungi in three types of tree peonies were investigated. Endophytic fungi of three types of tree peonies were isolated and identified. The diversity was analyzed. Bayesian trees constructed by MrBayes 3.2.6 after phylogenetic analysis of the ITS sequences. The endophytic fungi potential for synthesis of natural products was assessed by means of detecting NRPS and PKS gene sequences. In total, 364 endophytic fungi isolates representing 26 genera were recovered from Paeonia ostii Feng Dan, Paeonia ostii Luoyang Feng Dan, and Paeonia suffruticosa Luoyang Hong. More culturable endophytic fungi appeared in P. suffruticosa Luoyang Hong (206) compared with P. ostii Feng Dan (60) and P. ostii Luoyang Feng Dan (98). The fungal community of P. ostii Feng Dan had the highest richness and diversity. PKSs and NRPS detection rates of endophytic fungi from P. ostii Feng Dan are both the highest among the three types of tree peonies. Results indicate that endophytic fungus is an important factor of Daodi Cortex Moutan forming, and endophytic fungi in peony are related to genuineness of Cortex Moutan.

Diversity and communities of culturable endophytic fungi from different tree peonies (geoherbs and non-geoherbs), and their biosynthetic potential analysis

Abstract To know more about the potential roles of endophytic fungi in the formation mechanism of Daodi medicinal material, diversity and communities of culturable endophytic fungi in three types of tree peonies were investigated. Endophytic fungi of three types of tree peonies were isolated and identified. The diversity was analyzed. Bayesian trees constructed by MrBayes 3.2.6 after phylogenetic analysis of the ITS sequences. The endophytic fungi potential for synthesis of natural products was assessed by means of detecting NRPS and PKS gene sequences. In total, 364 endophytic fungi isolates representing 26 genera were recovered from Paeonia ostii 'Feng Dan', Paeonia ostii 'Luoyang Feng Dan', and Paeonia suffruticosa 'Luoyang Hong'. More culturable endophytic fungi appeared in P. suffruticosa 'Luoyang Hong' (206) compared with P. ostii 'Feng Dan' (60) and P. ostii 'Luoyang Feng Dan' (98). The fungal community of P. ostii 'Feng Dan' had the highest richness and diversity. PKSs and NRPS detection rates of endophytic fungi from P. ostii 'Feng Dan' are both the highest among the three types of tree peonies. Results indicate that endophytic fungus is an important factor of Daodi Cortex Moutan forming, and endophytic fungi in peony are related to genuineness of Cortex Moutan.

Diversity and communities of culturable endophytic fungi from different tree peonies (geoherbs and non-geoherbs), and their biosynthetic potential analysis

To know more about the potential roles of endophytic fungi in the formation mechanism of Daodi medicinal material, diversity and communities of culturable endophytic fungi in three types of tree peonies were investigated. Endophytic fungi of three types of tree peonies were isolated and identified. The diversity was analyzed. Bayesian trees constructed by MrBayes 3.2.6 after phylogenetic analysis of the ITS sequences. The endophytic fungi potential for synthesis of natural products was assessed by means of detecting NRPS and PKS gene sequences. In total, 364 endophytic fungi isolates representing 26 genera were recovered from Paeonia ostii ‘Feng Dan, Paeonia ostii ‘Luoyang Feng Dan, and Paeonia suffruticosa ‘Luoyang Hong. More culturable endophytic fungi appeared in P. suffruticosa ‘Luoyang Hong (206) compared with P. ostii ‘Feng Dan (60) and P. ostii ‘Luoyang Feng Dan (98). The fungal community of P. ostii ‘Feng Dan had the highest richness and diversity. PKSs and NRPS detection rates of endophytic fungi from P. ostii ‘Feng Dan are both the highest among the three types of tree peonies. Results indicate that endophytic fungus is an important factor of Daodi Cortex Moutan forming, and endophytic fungi in peony are related to genuineness of Cortex Moutan.(AU)

Comparison of wavefront aberrations under cycloplegic, scotopic and photopic conditions using WaveScan.

PURPOSE: To evaluate the differences of wavefront aberrations under cycloplegic, scotopic and photopic conditions. METHODS: A total of 174 eyes of 105 patients were measured using the wavefront sensor (WaveScan® 3.62) under different pupil conditions: cycloplegic 8.58 ± 0.54 mm (6.4 mm - 9.5 mm), scotopic 7.53 ± 0.69 mm (5.7 mm - 9.1 mm) and photopic 6.08 ± 1.14 mm (4.1 mm - 8.8 mm). The pupil diameter, standard Zernike coefficients, root mean square of higher-order aberrations and dominant aberrations were compared between cycloplegic and scotopic conditions, and between scotopic and photopic conditions. RESULTS: The pupil diameter was 7.53 ± 0.69 mm under the scotopic condition, which reached the requirement of about 6.5 mm optical zone design in the wavefront-guided surgery and prevented measurement error due to the pupil centroid shift caused by mydriatics. Pharmacological pupil dilation induced increase of standard Zernike coefficients Z(3)(-3), Z(4)(0) and Z(5)(-5). The higher-order aberrations, third-order aberration, fourth-order aberration, fifth-order aberration, sixth-order aberration, and spherical aberration increased statistically significantly, compared to the scotopic condition (P<0.010). When the scotopic condition shifted to the photopic condition, the standard Zernike coefficients Z(4)(0), Z(4)(2), Z(6)(-4), Z(6)(-2), Z(6)(2) decreased and all the higher-order aberrations decreased statistically significantly (P<0.010), demonstrating that accommodative miosis can significantly improve vision under the photopic condition. Under the three conditions, the vertical coma aberration appears the most frequently within the dominant aberrations without significant effect by pupil size variance, and the proportion of spherical aberrations decreased with the decrease of the pupil size. CONCLUSIONS: The wavefront aberrations are significantly different under cycloplegic, scotopic and photopic conditions. Using the wavefront sensor (VISX WaveScan) to measure scotopic wavefront aberrations is feasible for the wavefront-guided refractive surgery.

Comparison of wavefront aberrations under cycloplegic, scotopic and photopic conditions using WaveScan / Comparação de aberrações de frente de onda sob cicloplegia, condições escotópica e fotópica usando WaveScan

PURPOSE: To evaluate the differences of wavefront aberrations under cycloplegic, scotopic and photopic conditions. METHODS: A total of 174 eyes of 105 patients were measured using the wavefront sensor (WaveScan® 3.62) under different pupil conditions: cycloplegic 8.58 ± 0.54 mm (6.4 mm - 9.5 mm), scotopic 7.53 ± 0.69 mm (5.7 mm - 9.1 mm) and photopic 6.08 ± 1.14 mm (4.1 mm - 8.8 mm). The pupil diameter, standard Zernike coefficients, root mean square of higher-order aberrations and dominant aberrations were compared between cycloplegic and scotopic conditions, and between scotopic and photopic conditions. RESULTS: The pupil diameter was 7.53 ± 0.69 mm under the scotopic condition, which reached the requirement of about 6.5 mm optical zone design in the wavefront-guided surgery and prevented measurement error due to the pupil centroid shift caused by mydriatics. Pharmacological pupil dilation induced increase of standard Zernike coefficients Z3-3, Z4(0) and Z5-5. The higher-order aberrations, third-order aberration, fourth-order aberration, fifth-order aberration, sixth-order aberration, and spherical aberration increased statistically significantly, compared to the scotopic condition (P<0.010). When the scotopic condition shifted to the photopic condition, the standard Zernike coefficients Z4(0), Z4², Z6-4, Z6-2, Z6² decreased and all the higher-order aberrations decreased statistically significantly (P<0.010), demonstrating that accommodative miosis can significantly improve vision under the photopic condition. Under the three conditions, the vertical coma aberration appears the most frequently within the dominant aberrations without significant effect by pupil size variance, and the proportion of spherical aberrations decreased with the decrease of the pupil size. CONCLUSIONS: The wavefront aberrations are significantly different under cycloplegic, scotopic and photopic conditions. Using the wavefront sensor (VISX WaveScan) to measure scotopic wavefront aberrations is feasible for the wavefront-guided refractive surgery.

OBJETIVO: Avaliar as diferenças de aberrações de frente de onda, em diferentes condições pupilares: sob cicloplegia, escotópica e fotópica. MÉTODOS: Um total de 174 olhos de 105 pacientes foram avaliados utilizando o sensor de frente de onda (WaveScan® 3.62) em diferentes condições pupilares: sob cicloplegia 8,58 ± 0,54 mm (6.4 mm-9.5 mm), escotópica 7,53 ± 0,69 mm (5,7 mm - 9,1 mm) e fotópica 6,08 ± 1,14 mm (4,1 mm - 8,8 mm). Diâmetro da pupila, coeficientes de Zernike, RMS ("Root Mean Square") das aberrações de alta ordem e as aberrações dominantes foram comparados entre as condições sob cicloplegia e escotópica, e entre as condições escotópica e fotópica. RESULTADOS: O diâmetro da pupila foi 7,53 ± 0.69 mm sob a condição escotópica e atingiu a exigência de cerca de 6,5 mm de zona óptica na cirurgia baseada em análise de frentes de ondas, evitando erros de medição consequentes à mudança de centroide pupilar provocada por midriáticos. A dilatação farmacológica da pupila induziu aumento dos coeficientes de Zernike Z3-3, Z4(0) e Z5-5. As aberrações de mais alta ordem (terceira, quarta, quinta e sexta ordem) e a aberração esférica aumentaram de forma estatisticamente significativa, em comparação com a condição escotópica (P<0,010). Quando a condição escotópica se mudou para a condição fotópica, os coeficientes de Zernike Z4(0), Z4², Z6-4, Z6-2, Z6² e todas as aberrações de alta ordem diminuíram de forma estatisticamente significativa (P<0,010), demonstrando que a miose acomodativa pode significativamente melhorar a visão sob a condição fotópica. Sob as três condições, a aberração coma vertical apareceu mais frequentemente dentro das aberrações dominantes, sem influência significativa da variação do tamanho da pupila, e a proporção de aberração esférica diminuiu com a diminuição do tamanho da pupila. CONCLUSÕES: As aberrações de frente de onda são significativamente diferentes sob cicloplegia, condições escotópica e fotópica. O uso do sensor de frentes de onda (VISX WaveScan) para medir as aberrações de frente de onda escotópicas é uma opção viável para a cirurgia refrativa baseada em análise de frentes de onda.