Attempted retrieval of guidewire fragment using the twisting wire technique causes coronary perfusion: Case report.

RATIONALE: Guidewire fracture is one of the biggest risks of percutaneous coronary intervention, twisting wire technique is very useful for retrieving the fractured wire, but the potential risks have been inadequately reported. Herein, we present a case of retrieval of guidewire fragments using the twisting wire technique that causes coronary perfusion. PATIENT CONCERNS: A 37-year-old male patient was admitted to our hospital for elective percutaneous coronary intervention of the left circumflex coronary artery. CLINICAL FINDINGS: For chronic total occlusion of the distal left circumflex coronary artery, antegrade recanalization by wire escalation, and parallel wire techniques were attempted. However, we shockingly found that the BMW guidewire, anchored in the right coronary artery, spontaneously fractured from the proximal right coronary artery, and a lengthy fragment of the guidewire remained in the coronary. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Many attempts were made to retrieve the remnant guidewire including the twisting wire technique, which leads to the perforation of the coronary. OUTCOMES: Finally, percutaneous retrieving procedures were stopped in favor of surgical extraction via a small coronary arteriotomy. This procedure was successful. LESSONS: To the best of our knowledge, the present case is the first reported spontaneous fracture of the guidewire. Leaving such a lengthy remnant guidewire in the artery, or leaving stenting over the wire, would impose a high risk of coronary thrombosis, perforation, and embolization. Yet, the perforation of the artery that occurred in this case, which could have had life-threatening consequences, resulted from our attempts to retrieve the guidewire using the twisting wire technique.

Risk factors for postoperative delirium in geriatric patients with hip fracture: A systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis was conducted to identify the potential risk factors for postoperative delirium in geriatric patients with hip fracture. Methods: PubMed, EMBASE, and Cochrane Library were searched from inception until December 31st, 2021. A combined searching strategy of subject words and free words was adopted. Studies involving risk factors for postoperative delirium in elderly patients undergoing hip fracture surgeries were reviewed. Qualities of included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled and a meta-analysis was performed using Review Manager 5.3. Results: A total of 37 studies were included. The following risk factors were significant: advanced age (per year increase) (OR: 1.05, 95% CI 1.04-1.07), age>80 years (OR: 2.26, 95% CI 1.47-3.47), male (OR: 1.53, 95% CI 1.37-1.70), preoperative cognitive impairment (OR:3.20, 95% CI 2.12-4.83), preoperative dementia (OR: 2.74, 95% CI 2.18-3.45), preoperative delirium (OR: 9.23, 95% CI 8.26-10.32), diabetes (OR: 1.18, 95% CI 1.05-1.33), preoperative functional dependence (OR: 1.31, 95% CI 1.11-1.56), ASA level (per level increase) (OR: 1.63, 95% CI 1.04-2.57), ASA level≥3(OR: 1.76, 95% CI 1.39-2.24), low albumin (OR: 3.30, 95% CI 1.44-7.55), medical comorbidities (OR: 1.15, 95% CI 1.06-1.25), Parkinson's disease (OR: 4.17, 95% CI 1.68-10.31) and surgery delay>48 h (OR: 1.90, 95% CI 1.36-2.65). Conclusions: Clinicians should be alert to patients with those risk factors. To identify the risk factors more precisely, more research studies with larger sample size and better design should be conducted.

[Risk factors analysis for postoperative mortality of elderly patients with femoral neck fracture undergoing hemiarthroplasty].

OBJECTIVE: To analyze the risk factors for postoperative mortality of the elderly patients with femoral neck fracture undergoing hemiarthroplasty. METHODS: Patients who underwent hemiarthroplasty for femoral neck fractures between January 2011 and December 2015 were enrolled as object. One hundred and nine patients who met the selection criteria were included in the study, and the clinical data were collected, including gender, age, time from admission to surgery, comorbidities, and preoperative hemoglobin level and nutritional status. Univariate analysis and Cox proportional hazard regression model were used to screen the risk factors for postoperative mortality. RESULTS: The 1-year and 2-year mortalities were 6.4% (7/109) and 17.4% (19/109), respectively. Univariate analysis showed that the age, preoperative hemoglobin level and nutritional status were the influencing factors of postoperative mortality in the elderly patients with femoral neck fractures treated with hemiarthroplasty ( P<0.05). Multivariate analysis showed that the age≥80 years and malnutrition were the independent risk factors for postoperative mortality ( P<0.05). CONCLUSION: To improve the clinical outcomes, perioperative risk should be comprehensively evaluated by multidisciplinary and perioperative management should be strengthened in the elderly patients with femoral neck fracture, especially those with advanced age and malnutrition, for the high postoperative mortality.

Evaluation of four scoring systems in prognostication of acute pancreatitis for elderly patients.

BACKGROUND: To evaluate the ability of four scoring systems (Ranson, BISAP, Glasgow, and APACHE II) to predict outcomes of acute pancreatitis (AP) in elderly patients. METHODS: This was a retrospective study of 918 patients presenting with AP at Zhongda Hospital Southeast University, from January 2015 to December 2018. We divided patients into two groups: 368 patients who were ≥ 60 years old, and 550 patients who were < 60 years old. Four scoring systems were used to analyze all patients. RESULTS: The severity of the disease, and mortality were significantly different between the two groups (p < 0.05), while the difference between the two groups about pancreatic necrosis is statistically insignificant (p = 0.399). The differences of the AUCs (Area under curves) for prediction of outcome of SAP (severe acute pancreatitis) between the two groups were statistically significant for Ranson and APACHE II (p < 0.05), but not for the differences between BISAP and Glasgow. All the four scoring systems were similar in terms of prediction of pancreatic necrosis and death in both groups. CONCLUSIONS: Prediction of severity, pancreatic necrosis, and death in AP for elderly patients can be performed very well by using BISAP. APACHE II is more suitable for younger patients when dealing with severity. Ranson and Glasgow can be used to evaluate all AP patients in most cases; however, Ranson is more effective for younger patients when used to assess severity.

[Research progress of multidisciplinary team co-management models for geriatric hip fracture treatment].

OBJECTIVE: To summarize the research progress of multidisciplinary team (MDT) co-management models in the clinical treatment of geriatric hip fractures. METHODS: The literature about types and characteristics of MDT for geriatric hip fracture treatment were extensively reviewed, and the advantages of its clinical application were analysed and summarised. Finally, the MDT model and characteristics of geriatric hip fracture in the Zhongda Hospital affiliated to Southeast University were introduced in detail. RESULTS: Clinical models of MDT are diverse and have their own characteristics, and MDT can shorten the length of stay and waiting time before operation, reduce the incidence of internal complications, save labor costs, and reduce patient mortality. CONCLUSION: The application of MDT in the treatment of geriatric hip fracture has achieved remarkable results, which provides an optimal scheme for the treatment of geriatric hip fracture.

[Risk factors analysis for postoperative mortality of elder patients with intertrochanteric fractures].

OBJECTIVE: To analyze the risk factors for postoperative mortality of elder patients with intertrochanteric fractures. METHODS: Patients with intertrochanteric fractures who underwent proximal femoral interlocking intramedullary nail fixation between January 2014 and December 2015 were enrolled in the study. Among them, 135 patients who met the selection criteria were included in the study, and the clinical data were collected, including gender, age, time from admission to surgery, comorbidities, and preoperative hemoglobin, albumin, and total lymphocyte count (TLC), and nutritional status. Univariate analysis and Cox proportional hazards regression model were used to screen the risk factors for postoperative mortality. RESULTS: Twenty-seven patients (20.0%) died within 2 years after surgery, and 16 (11.9%) died within 1 year after surgery. Univariate analysis showed that age, coronary atherosclerotic heart disease, number of comorbidities, preoperative hemoglobin and albumin levels were the influencing factors of postoperative mortality in elder patients with intertrochanteric fractures treated with proximal femoral interlocking intramedullary nail fixation (P<0.05). Multivariate analysis showed that age (≥80 years), combined more than 2 medical diseases, and preoperative albumin (<35 g/L) were the independent risk factors for postoperative mortality (P<0.05). CONCLUSION: To improve the clinical outcomes, perioperative risk should be comprehensively evaluated and perioperative management strengthened in the elder patients with intertrochanteric fractures, especially those with advanced age, more combined diseases, and low albumin, for the high postoperative mortality.

ANGPTL2 regulates autophagy through the MEK/ERK/Nrf-1 pathway and affects the progression of renal fibrosis in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus. The present study aims to explore whether angiopoietin-like protein 2 (ANGPTL2) can promote renal tissue fibrosis in DN. MATERIALS AND METHODS: Models includes diabetic SD rats induced by streptozotocin (STZ) and high glucose (HG)-stimulated HK-2 cells. qRT-PCR, western blot and immunohistochemical analysis were performed to explore ANGPTL2 expression. The renal injury and fibrosis were assessed using hematoxylin-eosin staining (H&E) and Masson trichrome staining. Immunofluorescence was conducted to detect the expression of collagen IV and LC3II. The levels of pro-inflammatory factors IL-6, -1ß, TNF-α and ANGPTL2 were assessed by an ELISA, and nitric oxide (NO) production was determined using Griess method. Protein levels of iNOS, PTEN, fibronectin (FN), collagen I, IV, p62, beclin1 and MEK/ERK/Nrf-1 pathway in DN rats and HK-2 cells were determined, respectively. RESULTS: When compared with normal rats, DN rats experienced severe renal injury and fibrosis and showed decreased LC3II and beclin1, increased PTEN, FN, collagen I and IV, p62, NO, iNOS and ANGPTL2 in kidney. The pro-inflammatory factors and ANGPTL2 were markedly elevated. Again, knockdown of ANGPTL2 caused an increase in MEK, p-ERK, Nrf-1, LC3II, beclin1, and a decrease in PTEN, FN, collagen I and IV, p62, NO, iNOS and pro-inflammatory factors of HK-2 cells. Furthermore, knockdown of MEK/ERK reversed these changes. CONCLUSION: ANGPTL2 may serve an important role in the autophagy of DN and activate MEK/ERK/Nrf-1 pathway, which may therefore have potential as a treatment to prevent renal fibrosis in DN.

[Clinical application of multidisciplinary team co-management in geriatric hip fractures].

OBJECTIVE: To observe the clinical application of multidisciplinary team (MDT) treatment in the management of geriatric hip fractures and evaluate its effectiveness. METHODS: The clinical data of 76 elderly patients with hip fracture managed by MDT approach between August 2016 and February 2018 (MDT group) were retrospectively analyzed and compared with 102 patients managed by traditional orthopedics approach between January 2014 and December 2015 (conventional group). There was no significant difference in gender, age, fracture type, surgical procedure, and other general data between the two groups ( P>0.05). However, the number of comorbidities in the MDT group was significantly higher than that in the conventional group ( t=6.295, P=0.000), and the proportion of the number of comorbidities between the two groups was also significantly different ( χ 2=28.442, P=0.000). The consultation rate and transfer rate, time to surgery, rate of surgery within 2 or 3 days, operation time, postoperative hospitalization stay, length of hospitalization stay, hospitalization expense, rate of loss to follow-up, and mortality during hospitalization, 30-day mortality, 90-day mortality, and 1-year mortality after operation were compared between the two groups. RESULTS: The rates of total consultations of the conventional group and the MDT group were 56.86% (58/102) and 56.58% (43/76), respectively, and the rates of total transferred patients were 15.69% (16/102) and 15.79% (12/76), respectively, with no significant differences ( P>0.05). Among them, the proportion of patients who transferred into intensive care unit (ICU) in conventional group was significantly higher than that in MDT group and the rates of patients who received geriatric consultation or transferred into geriatric department in MDT group were both significantly higher than those in conventional group ( P<0.05). There was no significant difference in rates of other department consultation or transfer between the two groups ( P>0.05). The time to surgery, operation time, postoperative hospitalization stay, and length of hospitalization stay in MDT group were significantly less than those in conventional group, but the proportion of patients who received surgery within 3 days in MDT group was significantly higher than that in conventional group ( P<0.05). There was no significant difference in the proportion of patients who received surgery within 2 days ( χ 2=2.027, P=0.155). The hospitalization expenses of total patients, femoral neck fracture, and intertrochanteric fracture subgroups in MDT group were all significantly higher than those in conventional group ( P<0.05). However, there was no significant difference in hospitalization expense of subtrochanteric fracture subgroup between the two groups ( Z=-1.715, P=0.086). The rate of loss to follow-up in conventional group and MDT group was 6.86% (7/102) and 3.95% (3/76), respectively, with no significant difference ( χ 2=0.698, P=0.403). The mortalities at hospitalization, 1 month, 3 months, and 1 year after operation in conventional group were 0, 1.05% (1/95), 3.16% (3/95), and 7.37% (7/95), respectively, and in MDT group were 0, 0, 2.74% (2/73), 6.85% (5/73), respectively, showing no significant differences in mortalities between the two groups ( P>0.05). CONCLUSION: MDT model in the management of geriatric hip fractures has been shown to reduce time to surgery, postoperative hospitalization stay, length of hospitalization stay, operation time, and the proportion of patients who received ICU consultation or transferred into ICU. Furthermore, MDT can improve the capacity for developing operations for patients with complex medical conditions and make medical resources used more rationally.

Risk Factors and Prevention Strategies of Nosocomial Infection in Geriatric Patients.

INTRODUCTION: To investigate the risk factors of nosocomial infections (NIs) in geriatric department and the effectiveness of the proposed prevention strategy. METHODOLOGY: We studied 3370 cases of elderly patients who were hospitalized more than 48 hours from January 2015 to December 2017 in the Geriatrics Department of Zhongda Hospital, Southeast University. In order to reduce the infection rate, nutritional risk screening (NRS 2002) was used to evaluate the nutritional status of the patients; enteral nutritional suspension (TPF-FOS) was provided to the patients who were assessed to be necessary. RESULTS: Before prevention strategy was taken, the nosocomial infection rate was 3.3% (80 among 2413 patients) in our department. The most frequent NIs were pneumonia (60 cases) followed by urinary tract infection (30 cases). It is worth noting that the elderly patients are often associated with multiple infections: in our study, 15 patients have pneumonia and UTI at the same time. After prevention strategy was taken, the nosocomial infection rate reduced to 1.15% (11 among 957 patients) in our department. CONCLUSIONS: NIs are common in elderly patients. The improvement of the nutritional status of patients is effective in reducing the risks of NIs.

[Research status of the enhanced recovery after surgery in the geriatric hip fractures].

Objective: To summarize the latest developments in the enhanced recovery after surgery (ERAS) in the geriatric hip fractures and its perioperative therapy management. Methods: The recent original literature on the ERAS in the geriatric hip fractures were extensively reviewed, illustrating the concepts and properties of the ERAS in the geriatric hip fractures. Results: It has been considered to be associated with the decreased postoperative morbidity, reduced hospital length of stay, and cost savings to implement ERAS protocols, including multimodal analgesia, inflammation control, intravenous fluid therapy, early mobilization, psychological counseling, and so on, in the perioperative (emergency, preoperative, intraoperative, postoperative) management of the geriatric hip fractures. The application of ERAS in the geriatric hip fractures guarantees the health benefits of patients and saves medical expenses, which also provides basis and guidance for the further development and improvement of the entire process perioperative management in the geriatric hip fractures. Conclusion: Significant progress has been made in the application of ERAS in the geriatric hip fractures. ERAS protocols should be a priority for perioperative therapy management in the geriatric hip fractures.

Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice.

Glucose-stimulated insulin secretion (GSIS) is a highly regulated process involving complex interaction of multiple factors. Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) is a susceptibility gene for type 2 diabetes (T2D) and the risk alleles of the KCNQ1 gene appear to be associated with impaired insulin secretion. The role of KCNQ1 channel in insulin secretion has been explored by previous work in clonal pancreatic ß-cells but has yet to be investigated in the context of primary islets as well as intact animals. Genetic studies suggest that altered incretin glucagon-like peptide-1 (GLP-1) secretion might be a potential link between KCNQ1 variants and impaired insulin secretion, but this hypothesis has not been verified so far. In the current study, we examined KCNQ1 expression in pancreas and intestine from normal mice and then investigated the effects of chromanol 293B, a KCNQ1 channel inhibitor, on insulin secretion in vitro and in vivo. By double-immunofluorescence staining, KCNQ1 was detected in insulin-positive ß-cells and GLP-1-positive L-cells. Administration of chromanol 293B enhanced GSIS in cultured islets and intact animals. Along with the potentiated insulin secretion during oral glucose tolerance tests (OGTT), plasma GLP-1 level after gastric glucose load was increased in 293B treated mice. These data not only provided new evidence for the participation of KCNQ1 in GSIS at the level of pancreatic islet and intact animal but also indicated the potential linking role of GLP-1 between KCNQ1 and insulin secretion.

MicroRNA-155 inhibits angiotensin II-induced vascular smooth muscle cell proliferation.

BACKGROUND: MicroRNA-155 (miR-155) is a multifunctional signal microRNA that participates in a variety of cardiovascular diseases and is involved in physiological and pathological processes in different cell types. OBJECTIVE: The objective of this article is to examine the effect of miR-155 on angiotensin II (Ang II)-induced primary mice vascular smooth muscle cell (VSMC) proliferation. METHODS: Primary cultured VSMCs from the aorta of C57/BL6 mice were incubated with Ang II and miR-155. Cells were counted using CCK-8 and EdU, and flow cytometric analysis of cell cycle progression was performed. Angiotensin II 1 type receptor (AT1R) gene and protein expression were measured by real-time polymerase chain reaction and Western blotting. RESULTS: 1) Ang II increased the viability of VSMCs in a dose- and time-dependent manner. 2) miR-155 opposed the Ang II-induced increase in VSMC viability. 3) miR-155 inhibited Ang II-induced proliferation of VSMCs. 4) miR-155 increased the number of VSMCs in the G1 phase compared to G2 and M cell cycle phases. 5) miR-155 decreased ATR1 gene and protein expression. CONCLUSION: miR-155 downregulation of Ang II-induced VSMC viability identifies it as an important regulator of cell proliferation.

Quercetin improves insulin resistance and hepatic lipid accumulation in vitro in a NAFLD cell model.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases in the absence of significant alcohol consumption. The aim of this study was to investigate the effect of quercetin on insulin resistance and lipid metabolic abnormalities in free fatty acid (FFA)- and insulin-induced HepG2 cell model of NAFLD, and to determine the possible underlying mechanism. Quercetin markedly improves hepatic lipid accumulation and decreases the levels of triglyceride (TG). The lipid-lowering effect of quercetin at concentrations between 0.1 and 100 µM demonstrated a dose-dependent pattern. Quercetin was found to enhance tyrosine phosphorylation in the insulin-signaling pathway and to downregulate the expression levels of the sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in quercetin-treated groups, compared to the control group. These results demonstrated that quercetin was able to improve insulin resistance and hepatic lipid accumulation by suppressing two lipogenesis gene expression levels of SREBP-1c and FAS. As a result, quercetin has the therapeutic potential for preventing or treating NAFLD and IR-related metabolic disorders.

The prognostic role of disseminated tumor cells detected in peripheral blood and bone marrow of colorectal cancer.

BACKGROUND/AIMS: Disseminated tumor cells (DTCs) have been associated with clinical outcome in various malignancies. The aim of this study is to examine the status of DTC in peripheral blood (PB) and bone marrow (BM) of colorectal cancer (CRC) and to evaluate its clinical significance. METHODOLOGY: A total of 75 CRC patients treated with radical resection were enrolled in this study. Nested RT-PCR was used to detect the 2 representative markers of DTC, carcinoembryonic antigen (CEA) and survivin. RESULTS: The frequencies of DTC detected in PB and BM were 52.0% (39/75) and 29.3% (22/75) respectively, and showed no correlations with each other (p>0.05), their combination increased the sensitivity to 65.3% (49/75). Furthermore, DTC positive either in PB or BM was correlated with lymph metastasis, advanced stage and adverse 2-year progression free survival (PFS). In a multivariate analysis using the Cox proportional hazard model, DTC positive in PB and/ or BM was an independent unfavorable prognostic factor for CRC apart from lymph metastasis and adjuvant chemotherapy. CONCLUSIONS: CEA and/or survivin-positive DTCs may be a promising biomarker for prognosis assessment in CRC.

XPA A23G polymorphism and lung cancer risk: a meta-analysis.

Case-control studies on the association between XPA A23G and lung cancer have provided either controversial or inconclusive results. To clarify the effect of XPA A23G on the risk of lung cancer, a meta-analysis of all case-control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effects models. The Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. For the homozygote GG and G allele carriers (GA + GG), the pooled ORs were 1.24 (95% CI 1.05-1.46; P = 0.27 for heterogeneity) and 1.30 (95% CI 1.13-1.51; P = 0.45 for heterogeneity) compared to the homozygous genotype (AA). In the stratified analysis by ethnicity, the ORs of the G allele carriers and the homozygote GG were 1.28 (95% CI 1.10-1.49; P = 0.07 for heterogeneity) and 1.42 (95% CI 1.04-1.93; P = 0.39 for heterogeneity) among non-Caucasians. No significant associations were found in the Caucasian population in any of the genetic models. When studies that were not in Hardy-Weinberg equilibrium (HWE) were corrected, the pattern of the results remained the same. Our results indicated a significantly decreased risk of lung cancer in non-Caucasians with the G allele.

Detection and Clinical Significance of DLC1 Gene Methylation in Serum DNA from Colorectal Cancer Patients.

OBJECTIVE: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is toevaluate the diagnostic role of DLC1gene methylationin the serum DNA from CRC patients. METHODS: This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed. RESULTS: Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls(8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients' clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. CONCLUSION: The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.

PAMAM-triamcinolone acetonide conjugate as a nucleus-targeting gene carrier for enhanced transfer activity.

The excellent transfection efficiency and viability are essential for successful gene therapy. It suggested that when bound to its glucocorticoid receptor, glucocorticoid steroid can dilate the nuclear pore complexes and facilitated the transport of pDNA into the nucleus. In this research, the two different degrees of substitution of PAMAM-triamcinolone acetonide (PAMAM-TA) conjugates were synthesised for efficient translocation of pDNA into the nucleus. The physicochemical properties of the polyplexes were investigated by agarose gel electrophoresis, Zeta-sizer and TEM. They both could form nano-size polyplexes with pDNA. The polyplexes were very stable and showed excellent buffering capacities, facilitating endosomal escape, and no obvious difference was found between them. The TA-conjugated PAMAM-mediated transfection of luciferase and EGFP genes showed better transfer activity than native PAMAM and was comparable to the PEI 25K (polyethylenimine), and lower cytotoxicity in HEK 293 and HepG 2 cells. Even with 10% serum, their transfer activity was still high relatively. In addition, confocal microscopy examination confirmed that the enhancing mechanism for enhanced gene transfer activity of PAMAM-TA conjugate may involve the nuclear translocation of the polyplex. The low substituted degree of TA to 0.22 did not interrupt its nuclear localization potency. These findings demonstrated that the TA-grafted PAMAM dendrimer is a potential candidate as a safe and efficient gene delivery carrier for gene therapy.