Depression and anxiety in cancer patient enrolled in clinical trials with serious adverse events.

OBJECTIVE: Drug-induced side effects, particularly serious adverse events (SAEs), often affect cancer patients enrolled in clinical trials. However, little is known about anxiety and depression in cancer patients who experienced SAEs. This study evaluated the prevalence of anxiety and depression in cancer patients enrolled in clinical trials who experienced SAEs and explored the risk factors. METHODS: A multi-center, cross-sectional survey was conducted in hospitals affiliated with the University of Science and Technology of China from December 2021 to November 2022. A total of 112 cancer patients who experienced SAEs while enrolled in clinical trials, and who completed the informed consent process and study questionnaires, were included in the final analysis. RESULTS: The rate of moderate-severe depression in cancer patients was 38.4% and that of moderate-severe anxiety was 13.4%. Among the patients who had moderate-severe anxiety, 93.3% had concurrent moderate-severe depression. Lower cognitive function and lower global quality of life were risk factors for depression in cancer patients who experienced SAEs. Pain, low emotional function, low global quality of life, and a high Impact of Events Scale score were risk factors for anxiety. CONCLUSIONS: Cancer patients enrolled in a clinical trial who experienced SAEs tended to be anxious and depressed, particularly the latter. These results indicate the need to evaluate anxiety and depression, and mental health treatment among cancer patients with SAEs in clinical trials.

Exosomal miR-let-7c-5p is involved in the cognitive function of type 2 diabetes mellitus patients by interleukin 10: A cross-sectional study.

BACKGROUND: Interleukin (IL)-10 plays a notable role in the inflammatory-associated mild cognitive impairment (MCI). We aimed to investigate whether IL-10 and its upstream factors exert an impact on MCI in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 117 T2DM patients were recruited and divided into Control group and MCI group based on the presence or absence of MCI. Clinical parameters were collected. The Montreal Cognitive Assessment (MoCA) was conducted for global cognitive function. Digit Span Test (DST), Verbal Fluency Test (VFT), and Trail Making Test-B (TMTB) were used to evaluate the executive functions of the diabetic patients. Trail Making Test-A (TMTA) was performed to examine the information processing speed function. Patients' scene memory was examined by Logical Memory Test (LMT). After the baseline data were compared, correlation and regression analyses were performed to explore the relationship among IL-10, miR-let-7c-5p and cognitive function. RESULTS: Compared to 80 patients in the control group, 37 patients in the MCI group exhibited lower IL-10 in plasma and higher miR-let-7c-5p levels in exosomes from plasma. The IL-10 level was negatively associated with MoCA. Likewise, miR-let-7c-5p levels were negatively correlated with IL-10 levels and MoCA. Elevated miR-let-7c-5p levels and decreased IL-10 levels are risk factors for MCI in T2DM patients. Increased miR-let-7c-5p and downregulated IL-10 may influence VFT and TMTB, respectively, associated with executive function. CONCLUSIONS: We demonstrated that IL-10 is correlated to the executive function of T2DM patients. Decreased IL-10 may result from the regulation of miR-let-7c-5p in exosomes.

Awareness of Clinical Research Coordinators Toward Ethics and Protection of Clinical Trial Patients.

PURPOSE: Clinical research coordinators (CRCs) play an important role in the protection of clinical trial participants and maintenance of ethical standards. However, limited data are available on the ethical cognition of CRCs. Understanding the knowledge, attitude, and practices (KAP) of CRCs toward ethics is essential to protect study participants and improve their compliance. METHODS: We conducted a descriptive, cross-sectional, quantitative study at 20 hospitals in Anhui province of China. A self-administered questionnaire was completed by 435 CRCs conducting clinical trials. RESULTS: The good knowledge, positive attitude, and good practice rates were 55.2%, 59.3%, and 79.5% respectively. Most CRCs (99.1%) were aware of the participants' rights. Only 127 (29.2%) and 140 (32.2%) CRCs were aware of measures to protect participants' rights and ethical guidelines regarding trials, respectively. In total, 59.6% of CRCs stated that ethical review might delay the start of a clinical trial. Marital status (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.83), CRC work experience (OR 0.11, 95% CI 0.02-0.75), and educational background (OR 0.31, 95% CI 0.13-0.76) affected the knowledge of CRCs regarding ethics. CONCLUSIONS: Some deficiencies were observed in the ethical knowledge and behavior of CRCs. Interventions to improve the ethical training of CRCs regarding study participant protection, international guidelines, and the role of ethical committees are essential when conducting clinical trials. Validated instruments should be constructed to assess the effectiveness of ethical training and measure the KAP of CRCs toward ethics.

The consistencies and inconsistencies between distal cholangiocarcinoma and pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Objective: To evaluate the consistencies and inconsistencies between distal cholangiocarcinoma (DCCA) and pancreatic ductal adenocarcinoma (PDCA) regarding their biological features and long-term prognosis. Methods: PubMed, the Cochrane Library, and EMBASE were searched to find comparative studies between DCCA and PDCA. RevMan5.3 and Stata 13.0 software were used for the statistical analyses. Results: Eleven studies with 4,698 patients with DCCA and 100,629 patients with PDCA were identified. Pooled results indicated that patients with DCCA had a significantly higher rate of preoperative jaundice (p = 0.0003). Lymphatic metastasis (p < 0.00001), vascular invasion (p < 0.0001), and peri-neural invasion (p = 0.005) were more frequently detected in patients with PDCA. After curative pancreaticoduodenectomy (PD), a significantly higher R0 rate (p < 0.0001) and significantly smaller tumor size (p < 0.00001) were detected in patients with DCCA. Patients with DCCA had a more favorable overall survival (OS) (p < 0.00001) and disease-free survival (DFS) (p = 0.005) than patients with PDCA. However, postoperative morbidities (p = 0.02), especially postoperative pancreatic fistula (POPF) (p < 0.00001), more frequently occurred in DCCA. Conclusion: Patients with DCCA had more favorable tumor pathological features and long-term prognosis than patients with PDCA. An early diagnosis more frequently occurred in patients with DCCA. However, postoperative complications, especially POPF, were more frequently observed in patients with DCCA.

Efficacy and safety of acupuncture combined with rehabilitation in the treatment of strephenopodia after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Strephenopodia is a common complication after stroke, which is easily neglected in the early stage of the disease and seriously affects the rehabilitation process of patients' limbs, and brings huge security risks and family burden. A large number of studies have confirmed that acupuncture combined with rehabilitation (ACR) has a significant effect on strephenopodia after stroke (SAS), but there is still a lack of systematic scientific evidence to support this argument. In this systematic review, we aimed to evaluate the efficacy and safety of ACR in the treatment of SAS, to provide evidence-based medical evidence for the clinical treatment of the disease. METHODS: We will search the following databases of 8 electronic databases from inception to January 2022: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge infrastructure (CNKI), Technology Periodical Database (VIP), WanFang Data, and China Biology Medicine (CBM). All relevant randomized controlled trials (RCTs) focus on ACR in the treatment of strephenopodia after stroke will be included. The primary outcome will be the Measurement of strephenopodia angle and Clinical Spasm Index Scale (CSI). The Secondary outcomes will include Holden Functional Walking Classification (FAC), Berg Balance Scale (BBS), and Modified Barthel Index Score (MBI). Two reviewers will independently conduct the Study selection and data extraction. The risk of bias will be evaluated according to the Cochrane tool. Risk ratio and 95% confidence intervals will be used to estimate the efficacy of treatment, and the grading of recommendations, assessment, development, and evaluation approach to rate the certainty of evidence. The data analysis will be analyzed using by RevMan5.4. RESULT: This study will provide a comprehensive evaluation of the efficacy and safety of ACR in the treatment of SAS, with a view of providing more reliable evidence-based solutions for SAS. CONCLUSIONS: The conclusion of this study will provide evidence to judge whether ACR is effective and safe in treating SAS. PROSPERO REGISTRATION NUMBER: CRD42021290960.

EMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with the post-stroke shoulder-hand syndrome: A Bayesian network meta-analysis.

Background: Post-stroke shoulder-hand syndrome (SHS), although not a life-threatening condition, may be the most distressing and disabling problem for stroke survivors. Thus, it is essential to identify effective treatment strategies. Physical therapy is used as a first-line option for treating SHS; however, it is unclear which treatment option is preferred, which creates confusion in guiding clinical practice. Our study aims to guide clinical treatment by identifying the most effective physical therapy interventions for improving clinical symptoms in patients with post-stroke SHS using Bayesian network meta-analysis. Methods: We conducted a systematic and comprehensive search of data from randomized controlled trials using physical therapy in patients with SHS from database inception to 1 July 2022. Fugl-Meyer Upper Extremity Motor Function Scale (FMA-UE) and pain visual analog score (VAS) were used as primary and secondary outcome indicators. R (version 4.1.3) and STATA (version 16.0) software were used to analyze the data. Results: A total of 45 RCTs with 3,379 subjects were included, and the intervention efficacy of 7 physical factor therapies (PFT) combined with rehabilitation training (RT) was explored. Compared with the control group, all the PFT + RT included were of statistical benefit in improving limb motor function and pain relief. Also, our study indicated that EMG biofeedback combined with RT (BFT + RT) [the surface under the cumulative ranking curve (SUCRA) = 96.8%] might be the best choice for patients with post-stroke SHS. Conclusion: EMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with post-stroke SHS according to our Bayesian network meta-analysis results. However, the above conclusions need further analysis and validation by more high-quality RCTs. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: CRD42022348743.

Comparison of the efficacy of acupuncture-related Therapies for post-stroke motor aphasia: A Bayesian network meta-analysis.

Background: Motor aphasia, which can affect the communication ability of patients and even triggers severe psychological disorders, is one of the most common sequelae after stroke. Acupuncture (a typical complementary alternative therapy) is frequently combined with speech training (ST) to treat post-stroke motor aphasia (PSMA) and presents significant efficacy. However, the most effective acupuncture intervention is still unknown. This study aims to analyze the efficacy of several acupuncture approaches combined with ST for PSMA to identify the best intervention for clinical decision-making by using network meta-analysis (NMA). Methods: Eight major databases were searched from the time of their establishment to March 2022. Clinical efficacy rate (CER) was used as the primary outcome indicator. R software (version 4.13.0) and STATA software (version 16.0) were used to analyze the data. Results: A total of 29 randomized controlled trials (RCTs) and six treatment regimens were included in this study. In the pair-wise meta-analysis, we found that the efficacy of scalp-tongue acupuncture (STA) combined with ST [OR = 8.30; 95% Credible interval (CrI): 3.87, 17.33], tongue acupuncture (TA) combined with ST (OR = 3.95; 95% CrI: 2.27, 6.89), scalp-body acupuncture (SBA) combined with ST (OR = 3.75; 95% CrI: 2.26, 6.22), scalp acupuncture (SA) combined with ST (OR = 2.95; 95% CrI: 1.74, 5.0), and body acupuncture (BA) combined with ST (OR = 2.30; 95% CrI: 1.26, 4.19) were significantly superior to that of ST. In addition, the efficacy of STA + ST was significantly superior to that of SA +ST (OR = 2. 82; 95% CrI: 1.24, 6.38) and BA + ST (OR = 3.61; 95% CrI: 1.40, 9.29). According to the surface under the cumulative ranking curve (SUCRA), STA + ST (SUCRA = 97.9%) may be the best treatment regimen to improve the clinical outcome in patients with PSMA. Conclusion: The NMA showed that STA combined with ST may be the best treatment to improve CER, compared with other combination treatments. However, since the overall quality and number of studies are limited, further RCTs with a large sample and multicenter are needed for further validation. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316081, identifier CRD42022316081.

The Predictive Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Levels of Diabetic Peripheral Neuropathy.

OBJECTIVE: This study was designed to assess the levels of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in diabetes patients to determine their prognostic value in predicting the disease of diabetic peripheral neuropathy (DPN). METHODS: We recruited 225 diabetes cases from the department of endocrinology of Anhui Provincial Hospital from August 2018 to October 2019. A total of 103 patients without diabetic peripheral neuropathy (DPN) were followed up for 18 months, and the number of patients of newly diagnosed DPN was counted. According to the results of neuroelectrophysiological examination, these patients were divided into the diabetes mellitus (DM) without DPN group and the DM with DPN group. The general information and results of blood samples were collected. The collected data were compared between groups, and the receiver operating characteristic curve (ROC) was drawn. The follow-up data were compared between groups and Binary Logistic regression analysis was performed. RESULTS: Patients with DPN shared distinct characteristics. For example, the patients were older, and had higher levels of inflammatory indicators (ie, levels of PLR and NLR), and lower level of indirect bilirubin, compared with patients without DPN. According to the receiver operating characteristic curve analysis, for type 1 diabetes, PLR showed the highest area under the curve (0.753). For type 2 diabetes, NLR showed the highest AUC of 0.602. For the follow-up results, patients with newly diagnosed DPN bad higher NLR level. CONCLUSION: If patients of type 1 and type 2 diabetes are combined with elevated level of PLR and NLR, respectively, they are more likely complicated with DPN. NLR and PLR could be used as predictors to help clinicians screening for DPN in different types of diabetes. For type 1 diabetes, if patients who were without DPN had higher NLR level, the risk of developing DPN in the future will be greatly increased.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Aedes aegypti HPX8C modulates immune responses against viral infection.

Mosquitoes act as vectors of numerous pathogens that cause human diseases. Dengue virus (DENV) transmitted by mosquito, Aedes aegypti, is responsible for dengue fever epidemics worldwide with a serious impact on human health. Currently, disease control mainly relies on vector targeted intervention strategies. Therefore, it is imperative to understand the molecular mechanisms underlying the innate immune response of mosquitoes against pathogens. In the present study, the expression profiles of immunity-related genes in the midgut responding to DENV infection by feeding were analyzed by transcriptome and quantitative real-time PCR. The level of Antimicrobial peptides (AMPs) increased seven days post-infection (d.p.i.), which could be induced by the Toll immune pathway. The expression of reactive oxygen species (ROS) genes, including antioxidant genes, such as HPX7, HPX8A, HPX8B, HPX8C were induced at one d.p.i. and peaked again at ten d.p.i. in the midgut. Interestingly, down-regulation of the antioxidant gene HPX8C by RNA interference led to reduction in the virus titer in the mosquito, probably due to the elevated levels of ROS. Application of a ROS inhibitor and scavenger molecules further established the role of oxygen free radicals in the modulation of the immune response to DENV infection. Overall, our comparative transcriptome analyses provide valuable information about the regulation of immunity related genes in the transmission vector in response to DENV infection. It further allows us to identify novel molecular mechanisms underlying the host-virus interaction, which might aid in the development of novel strategies to control mosquito-borne diseases.

Lipid Levels Related to Osteoporosis in Patients with Type 2 Diabetes.

OBJECTIVE: Osteoporosis is a systemic skeletal disorder characterizedby reduced bone mass, deteriorated bone structure. Various studies have tried to evaluate the association between lipid level and osteoporosis, but the results were proved to be controversial. The objectives of this study are to assess the correlation between BMD and serum lipid levels, to determine independent variables associated with osteoporosis and osteopenia in men and postmenopausal women with type 2 diabetes (T2D). MATERIALS AND METHODS: All participants of the study were carried out biochemical analysis of blood and the analysis of the lipid profile that included total cholesterol (TC) and triglyceride (TG). Physical examination and dual-energy X-ray absorptiometry examination were performed. Multiple linear regression and multivariate logistic regression were used to evaluate associations between serum TC and TG levels and the osteoporosis or osteopenia. RESULTS: The level of serum TG was directly correlated with BMD at the lumbar spine in all patients in multiple linear regression models. After adjusting for potential confounding factors, decreased level of serum TG was independent risk factor for osteoporosis(p=0.022) in T2D patients. It also showed that a greater BMI was protective factor for osteoporosis (p=0.019) and lower level of ß-CTX was an independent risk factor for osteopenia (p=0.008) and osteoporosis (p=0.001) in T2D patients. CONCLUSION: Among Chinese patients with type 2 diabetes, the decreased level of serum TG might indicate a risk of osteoporosis. Further research is needed to confirm the finding and to clarify the contradictions identified.

Olfactory assessment in the Chinese pediatric population.

Young children with olfactory disturbance are sometimes encountered in ENT clinics. We investigated the clinical applicability of olfactory testing to the pediatric population in China.One hundred and ninety-three healthy children aged 6 to 17 years were enrolled. All participants were asked for demographic information (age, sex, body mass index [BMI], and rating of olfactory function) in a structured questionnaire and underwent olfactory testing including T&T Olfactometer (T&T), odor discrimination (OD), and odor identification (OI) tests of Sniffin' Sticks.Age had a significant influence on the outcome of olfactory testing, sex, BMI, or self-rating had no influence. Children had better performance on T&T than OI and OD tests of Sniffin' Sticks.T&T and Sniffin' Sticks can be completed by Chinese children. Performance on olfactory tests increased with increasing age. T&T may be more suitable to assess olfactory function in the Chinese pediatric population.

N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion by Flaviviruses.

Transmission of flaviviruses by hematophagous insects such as mosquitoes requires acquisition of the virus during blood feeding on the host, with midgut as the primary infection site. Here, we report that N-glycosylation of the E protein, which is conserved among most flaviviruses, is critical for the Zika virus (ZIKV) to invade the vector midgut by inhibiting the reactive oxygen species (ROS) pathway of the mosquito immune system. Our data further show that removal of the ZIKV E glycosylation site prevents mosquito infection by flaviviruses via the oral route, whereas there is no effect on infection by intrathoracic microinjection, which bypasses the midgut. Interestingly, the defect in infection of the mosquito midgut by the mutant virus through blood feeding is rescued by reduction of the ROS level by application of vitamin C, a well-known antioxidant. Therefore, our data demonstrate that ZIKV utilizes the glycosylation on the envelope to antagonize the vector immune defense during infection.IMPORTANCE Most flaviviruses, including Zika virus (ZIKV), are transmitted between hosts by arthropod vectors, such as mosquitoes, which acquire the virus during a blood meal. Here, by mutagenesis, we found a major role of the N-glycosylation of flavivirus E protein in its transmission circle, facilitating its survival against the vector immune system during invasion of the mosquito midgut while blood feeding on the host. In spite of the extensive studies of the involvement of N-glycan modification of flavivirus E protein in virus-host interactions, we discovered its critical role in virus-vector interaction and the evolution of flavivirus. Given the deleterious effects of ZIKV on human health, this study might have a significant impact on development of novel transmission-blocking strategies.

CTL14, a recognition receptor induced in late stage larvae, modulates anti-fungal immunity in cotton bollworm Helicoverpa armigera.

C-type lectin (CTL) is usually considered as pattern recognition receptors in insect innate immunity. Here we found that CTL14 of Helicoverpa armigera was only activated in the fifth instar larvae not in the second instar by entomopathogen Beauveria bassiana infection. Recombinant CTL14 protein was found to form aggregates with zymosan and B. bassiana in vitro. Immunoprecipitation studies demonstrated that CTL14 interacted with serine proteinases (SP), serine proteinase inhibitor (serpin), prophenoloxidases (PPO) and vitellogenin (Vg) in the larval hemolymph. Furthermore, depletion of CTL14 using dsRNA led to dramatic decrease in the expression level of PPO1. Additionally, CTL14 depleted H. armigera decreased the resistance to fungal challenge. Taken together, our study showed the direct involvement of CTL14 in the anti-fungal immunity of H. armigera, which further explained the stronger immune responses in the fifth instar compared to the second instar larvae.

Functional study on the mutations in the silkworm (Bombyx mori) acetylcholinesterase type 1 gene (ace1) and its recombinant proteins.

The acetylcholinesterase of Lepidoptera insects is encoded by two genes, ace1 and ace2. The expression of the ace1 gene is significantly higher than that of the ace2 gene, and mutations in ace1 are one of the major reasons for pesticide resistance in insects. In order to investigate the effects of the mutations in ace1's characteristic sites on pesticide resistance, we generated mutations for three amino acids using site-directed mutagenesis, which were Ala(GCG)303Ser(TCG), Gly(GGA)329Ala(GCA) and Leu (TCT)554Ser(TTC). The Baculovirus expression system was used for the eukaryotic expression of the wild type ace1 (wace1) and the mutant ace1 (mace1). SDS-PAGE and Western blotting were used to detect the targeting proteins with expected sizeof about 76 kDa. The expression products were purified for the determination of AChE activity and the inhibitory effects of physostigmine and phoxim. We observed no significant differences in the overall activity of the wild type and mutant AChEs. However, with 10 min of physostigmine (10 µM) inhibition, the remaining activity of the wild type AChE was significantly lower than that of the mutant AChE. Ten min inhibition with 33.4 µM phoxim also resulted in significantly lower remaining activity of the wild type AChE than that of the mutant AChE. These results indicated that mutations for the three amino acids reduced the sensitivity of AChE to physostigmine and phoxim, which laid the foundation for future in vivo studies on AChE's roles in pesticide resistance.

The adverse effects of phoxim exposure in the midgut of silkworm, Bombyx mori.

The silkworm is an important economic insect. Poisoning of silkworms by organophosphate pesticides causes tremendous loss to the sericulture. In this study, Solexa sequencing technology was performed to profile the gene expression changes in the midgut of silkworms in response to 24h of phoxim exposure and the impact on detoxification, apoptosis and immune defense were addressed. The results showed that 254 genes displayed at least 2.0-fold changes in expression levels, with 148 genes up-regulated and 106 genes down-regulated. Cytochrome P450 played an important role in detoxification. Histopathology examination and transmission electron microscope revealed swollen mitochondria and disappearance of the cristae of mitochondria, which are the important features in insect apoptotic cells. Cytochrome C release from mitochondria into the cytoplasm was confirmed. In addition, the Toll and immune deficiency (IMD) signal pathways were all inhibited using qRT-PCR. Our results could help better understand the impact of phoxim exposure on silkworm.

Controlled gene delivery system based on thermosensitive biodegradable hydrogel.

PURPOSE: Currently, most pDNA delivery systems based on synthetic polymers are either nonbiodegradable or not sensitive to the release environment. The primary objective of this study was to develop and evaluate an aqueous-based, thermosensitive, biodegradable and biocompatible triblock copolymer to control pDNA delivery in vitro and in vivo. METHODS: The triblock copolymers, poly[ethylene glycol-b-(D, L-lactic acid-co-glycol acid)-b-ethylene glycol] (PEG-PLGA-PEG), were synthesized as previously described. The molecular weight and polydispersity of PEG-PLGA-PEG were monitored by gel permeation chromatography (GPC). The cytotoxicity of PEG-PLGA-PEG was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The release of 32P-labeled pDNA entrapped in aqueous dispersion of PEG-PLGA-PEG in 0.1 mol/L sodium phosphate buffer solution (pH 7.4) was studied at 37 degrees C under agitation. Gene transfection efficiency was evaluated in a skin wound model in CD-1 mice. RESULTS: The aqueous dispersion of PEG-PLGA-PEG flows freely at room temperature but form a gel at 37 degrees C body temperature. The in vitro degradation of PEG-PLGA-PEG lasted for more than 30 days. The cytotoxicity of PEG-PLGA-PEG evaluated in HEK 293 cells was significantly lower than that of poly-L-lysine hydrochloride. The release profile of supercoiled pDNA from the polymer followed the zero-order kinetics up to 12 days. Maximal gene expression of luciferase was at 24 h in the skin wound of CD-1 mice and by 72 h, the expression dropped by nearly 94%. CONCLUSION: These results suggest hydrogel formed by PEG-PLGA-PEG could be a promising platform for delivery of pDNA, which represents a novel strategy that may serve as a non-viral vector for gene therapy in wound healing.