Photopolymerizable, immunomodulatory hydrogels of gelatin methacryloyl and carboxymethyl chitosan as all-in-one strategic dressing for wound healing.

Microenvironment regeneration in wound tissue is crucial for wound healing. However, achieving desirable wound microenvironment regeneration involves multiple stages, including hemostasis, inflammation, proliferation, and remodeling. Traditional wound dressings face challenges in fully manipulating all these stages to achieve quick and complete wound healing. Herein, we present a VEGF-loaded, versatile wound dressing hydrogel based on gelatin methacryloyl (GelMA) and carboxymethyl chitosan (CMCS), which could be easily fabricated using UV irradiation. The newly designed GelMA-CMCS@VEGF hydrogel not only exhibited strong tissue adhesion capacity due to the interactions between CMCS active groups and biological tissues, but also possessed desirable extensible properties for frequently moving skins and joints. Furthermore, the hydrogel demonstrates exceptional abilities in blood cell coagulation, hemostasis and cell recruitment, leading to the promotion of endothelial cells proliferation, adhesion, migration and angiogenesis. Additionally, in vivo studies demonstrated that the hydrogel drastically shortened hemostatic time, and achieved satisfactory therapeutic efficacy by suppressing inflammation, modulating M1/M2 polarization of macrophages, significantly promoting collagen deposition, stimulating angiogenesis, epithelialization and tissue remodeling. This work contributes to the design of versatile hydrogel dressings for rapid and complete wound healing therapy.

Antibiotic resistant genes profile in the surface water of subtropical drinking water river-reservoir system.

To comprehensively understand antibiotic resistant genes (ARGs) profile in the subtropical drinking water river-reservoir system, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate the spatial-temporal characteristics of ARGs diversity, bacterial host and resistance mechanism, and to analyze the key environmental factors driving ARGs profile variation. The results indicated that a total of 440 ARGs were detected in the target system, and the ARGs distribution pattern in the reservoir was attributed to autologous evolution or the comprehensive influence of feeding river system. The predominant bacterial host at different sites showed similar variations to dominated ARGs, and Proteobacteria, Actinobacteria and Bacteroidetes harbored most ARGs at phylum level, which showed the highest proportions of 74%, 37% and 35%, respectively. Antibiotic efflux was the primary resistance mechanism in all samples from wet season (45%-60%), yet the samples from dry season exhibited multiple resistance mechanisms, including inactivation (37%-52%), efflux (44%), and target alteration (43%). The total relative abundances of ARGs in the target system ranged from 0.89 × 10-2 to 1.71 × 10-2, and seasonal variation had a more significant influence on ARGs abundance than spatial variation (R = 0.68, P < 0.01). Environmental factors analysis indicated that the concentrations of nitrite nitrogen and total organic carbon were significant factors explaining ARGs number and various resistance mechanism proportions (P < 0.01), accounting for 48.7% and 61.1% of the variation, respectively; ammonia nitrogen concentration, total organic carbon concentration, temperature and pH were the significant influence factors on the relative abundance of ARGs (P < 0.05), with standardized regression weights of 0.700, 1.414, 1.447, and 1.727, respectively. In summary, in the surface water of the target system, ARGs diversity was primarily driven by ARGs horizontal transfer and antibiotics biosynthesis. Nutrients mainly promoted ARGs abundance by providing abundant energy, rather than increasing bacterial reproductive capacity.

Planktonic microbial community and biological metabolism in a subtropical drinking water river-reservoir system.

To understand the dynamics of planktonic microbial community and its metabolism processes in subtropical drinking water river-reservoir system with lower man-made pollution loading, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate spatial-temporal characteristics of community profile and functional genes involved in biological metabolism, and to analyze the influence of environmental factors. The results indicated that Proteobacteria and Actinobacteria were the most diverse phyla with proportion ranges of 9%-80% in target system, and carbohydrate metabolism (5.76-7.12 × 10-2), amino acid metabolism (5.78-7.21 × 10-2) and energy metabolism (4.07-5.17 × 10-2) were found to be the dominant pathways of biological metabolism. Although there were variations in biological properties both spatially and temporally, seasonal variation had a greater influence on microbial community and biological metabolism, than locational differences. Regarding the role of environmental factors, this study revealed that microbial diversity could be affected by multiple abiotic factors, with total organic carbon, total phosphorus and temperature being more influential (absolute value of standardized regression weights >2.13). Stochastic processes dominated the microbial community assembly (R2 of neutral community model = 0.645), while niche-based processes differences represented by nutrients, temperature and pH level played secondary roles (R > 0.388, P < 0.01). Notably, the synergistic influences among the environmental factors accounted for the higher percentages of community variation (maximum proportion up to 17.6%). Additionally, pH level, temperature, and concentrations of dissolved oxygen, carbon and nitrogen were found to be the significant factors affecting carbon metabolism pathways (P < 0.05), yet only total organic carbon significantly affected on nitrogen transformation (P < 0.05). In summary, the microbial profile in reservoir is not completely dominated by that in feeding river, and planktonic microbial community and its metabolism in subtropical drinking water river-reservoir system are shaped by multiple abiotic and biotic factors with underlying interactions.

Treatment outcome of patients with stages I-II nasopharyngeal carcinoma after late course accelerated hyperfractionation radiotherapy alone.

OBJECTIVES: To follow up the efficacy and incidence of radiation-induced complications of late course accelerated fractionation (LCAF) radiotherapy in early-stage nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From December 1995 to November 2002, 158 patients with stages I-II NPC were admitted for radiotherapy alone. For the first two-thirds of the treatment, 2 daily fractions of 1.2 Gy were given to the primary lesion, 5 days per week to a total dose of 48 Gy/40 fractions, over a period of 4 weeks. From the 5th week, an accelerated hyperfractionation schedule was carried out. Two daily fractions of 1.5 Gy were given, to a total dose of 30 Gy/20 fractions over 2 weeks. Thus the total dose was 78 Gy in 60 fractions in 6 weeks. RESULTS: All patients completed the treatment. Acute mucositis: none in 3 patients, grade 1 in 32, grade 2 in 69, grade 3 in 51, and grade 4 in 3 patients. Five-year nasopharyngeal control and overall survival (OS) rate of T1 and T2 were 97.8%, 90.2% (p=0.380) and 88.6%, 81.4% (p=0.252), respectively. Five-year OS in N0 and N1 patients were 86.5% and 81.9% (p=0.033), respectively. Thirty-eight patients died, and the main cause of death was distant metastasis. Seventeen (11%) patients had radiation-induced cranial nerve palsy. CONCLUSION: With LCAF, treatment-related toxicities were acceptable. Five-year nasopharyngeal control and OS in T2 stage were improved. Main cause of death was distant metastasis. Patients with N1 had a relatively lower survival rate, which suggested that chemotherapy might be indicated for those patients.

The pattern of relapse and survival of elective irradiation of the upper neck for stage N0 nasopharyngeal carcinoma.

BACKGROUND: To investigate patterns of failure and survival rates of elective irradiation of upper neck in N0 nasopharyngeal carcinoma patients. METHODS: From February 1996 to November 2002, 97 patients without cervical lymph node involvement were admitted for radiotherapy alone. Before treatment, each patient underwent enhanced CT of nasopharynx and neck. All patients received radiotherapy to the nasopharynx, skull base, and upper neck drainage areas (including levels II, III, and VA). The upper neck was irradiated to a total dose of 50-56 Gy/25-28 fractions/5-5.6 weeks. For the primary tumor, 22 patients used conventional fractionation for a total dose of 70 Gy/35 fractions/7 weeks, and 75 patients used an accelerated hyperfractionationated schedule for a total dose of 78 Gy/60 fractions/6 weeks. RESULTS: The median follow-up of these 97 patients was 7.75 years. 10 patients had recurrences in the nasopharynx, 8 had distant metastasis, and 5 had recurrences in the cervical lymph nodes. Among the cervical lymph node failures, the areas of recurrence were in the II drainage areas in 4 patients who had neck dissections afterwards, and in IA drainage areas in 1 patient who also had recurrence in the nasopharynx. The causes of death were recurrence in the nasopharynx for 8 patients, 1 of these also had recurrence in the neck, distant metastases in 8 patients, and non-neoplastic diseases in 3 patients. CONCLUSIONS: The causes of failure of N0 patients with nasopharyngeal carcinoma after radiotherapy alone to the nasopharynx and upper neck were nasopharyngeal recurrence, distant metastasis, and cervical recurrence in order of frequency. Elective irradiation of upper neck (II, III, VA) is advised for stage N0 patients diagnosed by enhanced CT of neck. Cervical recurrence alone is rare, which did not greatly affect the long-term survival after salvage neck dissection.

Treatment outcomes and prognostic features in adenoid cystic carcinoma originated from the head and neck.

Surgery is the main treatment modality for adenoid cystic carcinoma (ACC) originated from the head and neck. However, the extensive local infiltrative and perineural spread related to this malignancy often cause difficulty to achieve high tumor control. The aim of this study is to evaluate the efficacy of postoperative radiotherapy (RT) in ACC, and to identify prognostic variables associated with treatment outcomes. A retrospective review of 101 patients diagnosed with ACC in the head and neck region was performed. T stage distribution was T1, 25; T2, 35; T3, 18; and T4, 23 patients. All patients were grouped into two arms: surgery alone or combined with postoperative radiotherapy. The 5-year local-regional control (LRC), overall survival (OS) and disease-free survival (DFS) rates for all the patients were 70.5%, 91.7% and 63.2%, respectively. On univariant analysis, postoperative radiotherapy did improve the 5-year LRC and DFS compared to surgery alone (81.0% vs. 53.4%, p=0.0003 and 71.3% vs. 50.0%, p=0.0052, respectively). And patients with T1-T2 lesions achieved better treatment outcomes, whereas stage T3-T4 was associated with high local failure and poor disease-free survival. Furthermore, multivariate analysis revealed that the addition of radiotherapy and early lesions were both favorite predictors for local control and survival rates. The prognosis for ACC of the head and neck was excellent. Surgery combined with postoperative radiotherapy significantly reduced the local failure, and further improved disease-free survival. Nevertheless, the relatively high distant metastasis was an obstacle of curing the ACC patients.

A phase III study of late course accelerated hyperfractionated radiotherapy versus conventionally fractionated radiotherapy in patients with nasopharyngeal carcinoma.

OBJECTIVE: To compare the efficacy and toxicity of late course accelerated hyperfractionated radiotherapy (LCAF) with conventionally fractionated (CF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). METHODS: Between March 1998 and November 2002, 200 eligible patients with NPC were randomized to receive either LCAF (48 Gy in 40 fractions, 2 fractions per day, 1.2 Gy/fraction, with an interval of ≥6 h, 5 d/wk, followed by 30 Gy in 20 fractions using 2 fractions per day, 1.5 Gy/fraction, 5 d/wk) or CF (35 fractions, 2.0 Gy/fraction/d, 5 d/wk, to a total dose of 70 Gy). RESULTS: All patients completed the treatment. Overall baseline characteristics of the study population of the 2 arms were well balanced. With a median follow-up of 6.9 years, the 5-year local control rate was higher in the LCAF arm (87.6% vs. 75.9%, P=0.044). The 5-year overall survival rates were 74.1% vs. 58.0% (P=0.024) for the LCAF arm and the CF arm, respectively. LCAF patients had a higher occurrence of acute mucositis and a more evident weight loss than CF patients, whereas incidence rates of radiation-induced damage to the central nervous system were similar in the 2 arms. CONCLUSIONS: LCAF achieved higher local control and overall survival rates than CF radiotherapy, without increasing radiation-related late complications such as cranial nerve palsy.

The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer.

BACKGROUND: High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. METHODS: 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. RESULTS: The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. CONCLUSIONS: The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

Anatomic and dosimetric changes during the treatment course of intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

Prognostic impact of primary tumor volume in patients with nasopharyngeal carcinoma treated by definitive radiation therapy.

OBJECTIVES/HYPOTHESIS: Tumor burden has been confirmed as one of the important indicators in disease control after treatment for various types of malignancies. This report aims to document the value of the primary tumor volume of nasopharyngeal carcinoma [gross tumor volume of the primary site (GTV-P)] in predicting the treatment outcome after high-dose definitive radiation therapy. STUDY DESIGN: A total of 154 patients with nasopharyngeal carcinoma were prospectively treated with accelerated hyperfractionated radiotherapy alone to a total dose of 78 Gy/60 fractions/6 weeks (biological effective dose = 88.2 Gy). METHODS: Patients were assessed for local control, disease-free survival and distant failure free survival. The GTV-P was calculated by summation of area technique after delineation of the primary tumor contours on computed tomography images. RESULTS: The median GTV-P was 14.5 mL for T1, 23.3 mL for T2, 35.8 mL for T3, and 50.9 mL for T4 diseases (P < .05). With a median follow-up of 61 months, the 5-year local failure-free rate, disease-free survival and distant failure-free survival rates were 89.4% versus 48.9% (P = .002), 56.6% versus 0% (P = .001), and 66.9% versus 16.5% (P = .0001), respectively, for patients whose GTV-P were < or =60 mL and >60 mL. Multivariate analysis revealed that GTV-P is an independent prognostic factorfor local control (hazard ratio = 3.568, P = .035). There fore, the GTV-P was significantly associated with the treatment outcome after high-dose radiation delivered in accelerated hyperfractionated schedule for nasopharyngeal cancer patients. CONCLUSIONS: Tumor volume is a reliable indicator for supplementing the T classification of the Tumor, Node, Metastasis staging system for predicting local control after definite radiation therapy.

Late course accelerated hyperfractionated radiotherapy of nasopharyngeal carcinoma (LCAF).

BACKGROUND AND PURPOSE: To study the efficacy of late course accelerated fractionated (LCAF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). The end-points were local control, radiation-induced complications, and factors influencing survival. PATIENTS AND METHODS: Between December 1995 and April 1998, 178 consecutive NPC patients were admitted for radiation treatment. The radiation beam used was (60)Co gamma or 6 MV X rays. For the first two-thirds of the treatment, two daily fractions of 1.2 Gy were given to the primary lesion, with an interval of > or =6h, 5 days per week to a total dose of 48 Gy/40 fractions, over a period of 4 weeks. For the last third of the treatment, i.e., beginning the 5th week of treatment, an accelerated hyperfractionated schedule was carried out. The dose per fraction was increased to 1.5 Gy, 2 fractions per day with an interval of > or =6h, the total dose for this part of the protocol was 30 Gy/20 fractions over 2 weeks. Thus the total dose was 78 Gy in 60 fractions in 6 weeks. RESULTS: All patients completed the treatment. Acute mucositis: none in 2 cases, Grade 1 in 43 cases, Grade 2 in 78 cases, Grade 3 in 52 cases, and Grade 4 in 3 cases. Local control rate: the 5 year nasopharyngeal local control rate was 87.7%, and the cervical lymph nodes local control rate was 85.7%. The 5-year distant metastasis rate was 26.1%, and 5 year survivals were 67.9%, 16 (9%) patients had radiation-induced cranial nerve palsy, 7(4%) patients had temporal lobe or brainstem damage. CONCLUSIONS: With this treatment schedule, patients' tolerance was good, local control and 5 year survivals were better than conventional fractionation schedules, and radiation-related late complications did not increase, as 5-year survival rates of conventional fractionation radiotherapy were only 58%. Randomized clinical trials are being carried out to further confirm the efficacy of LCAF for nasopharyngeal carcinoma.

Radiotherapy and prognostic factors for thymoma: a retrospective study of 175 patients.

PURPOSE: To assess the factors that predict local control and survival in patients with thymoma treated with adjuvant radiotherapy (RT) and suggest strategies for optimizing adjuvant RT. METHODS AND MATERIALS: The study population comprised 47 patients with noninvasive thymoma and 128 patients with invasive thymoma. Treatment was surgery in 175 patients and radiotherapy in 169 patients; 25 patients also received adjuvant chemotherapy. The clinical factors (age, histologic features, stage, presence of myasthenia gravis) and therapeutic factors (extent of operation, irradiation dose, and field size) were retrospectively recorded and accessed using multivariate analysis. RESULTS: The overall survival rate at 5 and 10 years was 86.4% and 80.6%, respectively. Only 2 patients had a relapse in the noninvasive group. None died of thymoma during the study period. The patients with invasive disease had a 5- and 10-year disease-free survival rate of 64.4% and 55.6%, respectively, with 24 intrathoracic failures, 14 extrathoracic failures, and 8 combined failures. The univariate and multivariate analyses showed that Mosaoka stage and extent of resection were the important prognostic factors for patient with invasive thymoma. The 5-year survival rate and local control rate was 96% and 96% for Stage II, 77.8% and 56.4% for Stage III, 56.6% and 42.7% for Stage lVa, and 35.6% and 21.6% for Stage IVb (p < 0.0001 among different stage groups), respectively. The 5-year local control rate in patients with the tumor bed irradiated was 68.2%, comparable to the group treated with an extended RT field (66.6%). Age, histopathologic findings, radiation dose, and presence of myasthenia gravis were not statistically significant prognostic factors. CONCLUSION: Disease stage and extent of resection affected the prognosis of invasive thymoma patients. Extending the radiation field prophylactically was not associated with greater local control and is of questionable value for patients with invasive thymoma.

Comparison between continuous accelerated hyperfractionated and late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma.

PURPOSE: To compare the treatment results and toxicity of continuous accelerated hyperfractionated (CAHF) and late-course accelerated hyperfractionated (LCAF) radiotherapy (RT) for esophageal carcinoma. METHODS AND MATERIALS: Between August 1996 and March 1999, 101 patients with squamous cell carcinoma of the esophagus were randomized into two groups: 49 to the CAHF group and 52 to the LCAF group. Patients in the CAHF group received RT at 1.5 Gy/fraction b.i.d. (6-h interval), 5 d/wk, to a total dose 66 Gy in 44 fractions during 4.4 weeks. The patients in the LCAF group received conventional fractionation RT, 1.8 Gy/fraction, to a dose of 41.4 Gy in 23 fractions during 4.6 weeks, followed by accelerated fractionation RT using reduced fields, b.i.d., at 1.5 Gy/fraction, with a minimal interval of 6 h between fractions. The total dose was 68.4 Gy in 41 fraction during 6.4 weeks. Patient age, gender, performance score, diet, lesion location, lesion length, stage, and fractionation (CAHF or LCAF) were entered into the univariate and multivariate analyses. RESULTS: All patients finished the treatment course, except for 1 patient in the CAHF group because of severe acute esophagitis. The rate of Grade I, II, and III acute bronchitis was 18.4% (9 of 49), 30.6% (15 of 49), and 8.2% (4 of 49) in the CAHF group and 13.5% (7 of 52), 21.2% (11 of 52), and 3.8% (2 of 52) in the LCAF group, respectively. However, the difference between the two groups was not statistically significant (p = 0.084). The rate of Grade I, II, III, and IV acute esophagitis was 6.1% (3 of 49), 32.7% (16 of 49), 46.9% (23 of 49), and 14.3% (7 of 49) in the CAHF group and 26.9% (14 of 52), 32.7% (17 of 52), 7.7% (4 of 52), and 1.9% (1 of 52) in the LCAF group, respectively. The difference was statistically significant (p < 0.001). The local control rate at 1, 2, and 3 years was 88.7%, 83.9%, and 55.9% in the CAHF group and 80.7%, 71.4%, and 57.1% in the LCAF group, respectively (p = 0.1251). The 1-, 2-, and 3-year survival rate was 79.6%, 51.6%, and 37.6% in the CAHF group and 80.0%, 57.6%, and 41.2% in the LCAF group, respectively (p = 0.5757). Multivariate analysis showed that age and lesion length were independent significant prognostic factors for local control rate, and age was for the overall survival rate. The fractionation schedule had no significant prognostic effect. CONCLUSION: CAHF and LCAF result in similar 1-, 2-, and 3-year local control and survival rates. CAHF resulted in more severe acute esophagitis and may be less well tolerated than LCAF. The treatment results after the CAHF and LCAF regimens were better than those of historical conventional RT.