1.Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design.
Jing YAN ; Hao ZHANG ; Guangfeng LI ; Jiacan SU ; Yan WEI ; Can XU
Acta Pharmaceutica Sinica B 2024;14(2):579-601
Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.
2.Long-term outcomes of intravascular ultrasound-guided drug-eluting stents implantation in patients with acute coronary syndrome: ULTIMATE ACS subgroup
Xiaofei GAO ; Leng HAN ; Xuesong QIAN ; Zhen GE ; Xiangquan KONG ; Shu LU ; Jing KAN ; Guangfeng ZUO ; Junjie ZHANG ; Shaoliang CHEN
Chinese Journal of Cardiology 2024;52(2):137-143
Objective:To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation.Methods:Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization.Results:ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions:This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.
3.The relationship between the expression of fibroblast growth factor 19 and insulin-like growth factor 1 in colorectal polyp tissues and the occurrence of colorectal adenomas
Hao WANG ; Haipeng WANG ; Yao YAO ; Dongyang WANG ; Ming CHEN ; Yanlai SUN ; Hao ZHANG ; Guangfeng DONG ; Zengjun LI
Chinese Journal of Oncology 2024;46(8):776-781
Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.
4.The relationship between the expression of fibroblast growth factor 19 and insulin-like growth factor 1 in colorectal polyp tissues and the occurrence of colorectal adenomas
Hao WANG ; Haipeng WANG ; Yao YAO ; Dongyang WANG ; Ming CHEN ; Yanlai SUN ; Hao ZHANG ; Guangfeng DONG ; Zengjun LI
Chinese Journal of Oncology 2024;46(8):776-781
Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.
5.Application of group guidance based on intelligent communication matrix in patients with type 2 diabetes mellitus
Cuixiang XUAN ; Yan HU ; Lanlan ZHANG ; Fang LI ; Guangfeng TANG ; Daoqin ZHANG ; Yun CHEN ; Shiguang LI
Chinese Journal of Modern Nursing 2024;30(3):384-388
Objective:To explore the application effect of group guidance based on intelligent communication matrix in patients with type 2 diabetes mellitus (T2DM) .Methods:Using the convenient sampling method, a total of 60 T2DM patients with poor self-management ability who scored less than 19.6 on Summary of Diabetes Self Care Activities (SDSCA) in the Affiliated Chuzhou Hospital of Anhui Medical University were selected as the research objects from May to June 2020. They were randomly divide into the observation group ( n=30) and the control group ( n=30). The observation group was given continuous group guidance based on intelligent communication matrix, while the control group was given routine health guidance. The SDSCA score, body mass index and glycosylated hemoglobin (HbA1c) before and after intervention were compared between the two groups. Results:After intervention, the SDSCA score of the observation group was higher than that of the control group, HbA1c was lower than that of the control group and body mass index was lower than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The group guidance based on intelligent communication matrix can improve the self-management level of T2DM patients and reduce their body mass index and HbA1c levels, which has clinical application value.
6.Effects of G protein-coupled receptor 55 antagonist CID16020046 on renal fibrosis in mice
Yu ZHANG ; Mi BAI ; Jia HE ; Shuang XU ; Yuxian GUO ; Runxin ZENG ; Guangfeng LONG ; Aihua ZHANG
Chinese Journal of Nephrology 2024;40(8):646-656
Objective:To explore the effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis.Methods:(1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK-49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF-β1) was applied in the NRK-49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group ( n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results:(1) After NRK-49F cells were stimulated by TGF-β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF-β1 group and TGF-β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF-β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α-SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α-SMA were lower in the TGF-β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group ( P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α-SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions:CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.
7.Mechanism of hsa_circRNA_0000596 in promoting invasion and metastasis of cervical cancer cells
Guangfeng ZHANG ; Jue CHEN ; Chenghai WANG
Journal of Clinical Medicine in Practice 2024;28(20):6-11
Objective To investigate the mechanism of hsa_circRNA_000596 (circ-596) in promoting invasion and metastasis of cervical cancer cells. Methods The cervical squamous cell carcinoma (CSCC) tissue, normal cervical tissue adjacent to cancer and clinical data of 69 cases with CSCC were collected. RNA
8.Effectiveness of fascial tissue flaps and skin flaps with layered sutures for repair of wounds after excision of sacrococcygeal pilonidal sinus.
Wanghaonan CHEN ; Mingyue ZHANG ; Kerong TAO ; Xing YOU ; Guangfeng SUN
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(4):478-481
OBJECTIVE:
To investigate the feasibility and effectiveness of fascial tissue flaps and skin flaps with layered sutures for repairing wounds after excision of sacrococcygeal pilonidal sinus.
METHODS:
Between March 2019 and August 2022, 9 patients with sacrococcygeal pilonidal sinus were admitted, including 7 males and 2 females with an average age of 29.4 years (range, 17-53 years). The disease duration ranged from 1 to 36 months, with a median of 6 months. There were 7 cases with obesity and dense hair, 3 cases with infection, and 2 cases with positive bacterial culture of sinus secretion. The wound area after excision ranged from 3 cm×3 cm to 8 cm×4 cm, with a depth of 3-5 cm, reaching the perianal or caudal bone; there were 2 cases with perianal abscess formation and 1 case with caudal bone inflammatory edema. Enlarged resection was performed during operation, and the fascial tissue flap and skin flap were designed and excised at both left and right sides of the buttock, ranging from 3.0 cm×1.5 cm to 8.0 cm×2.0 cm. A cross drainage tube was placed at the bottom of the wound, and the fascial tissue flap and skin flap were advanced and sutured in three layers, namely, 8-string sutures in the fascial layer, barbed wire reduction sutures in the dermis, and interrupted skin sutures.
RESULTS:
All 9 patients were followed up 3-36 months, with an average of 12 months. All incisions healed by first intention, and no complication such as incisional dehiscence or infection in the operative area occurred. There was no recurrence of sinus tracts, the shape of gluteal sulcus was satisfactory, both sides of buttocks were symmetrical, local incision scar was concealed, and the shape disruption was minimal.
CONCLUSION
Fascial tissue flaps and skin flaps with layered sutures for repairing wounds after excision of sacrococcygeal pilonidal sinus can effectively fill the cavity and reduce the incidence of poor incision healing, with the advantages of small trauma and simple operation.
Male
;
Female
;
Humans
;
Adult
;
Pilonidal Sinus/surgery*
;
Treatment Outcome
;
Surgical Flaps
;
Plastic Surgery Procedures
;
Skin Transplantation
;
Soft Tissue Injuries/surgery*
;
Sutures
;
Perforator Flap
9.Application of hairpin shaped incision combined with cover-lifting flap in plastic surgery of huge fat pad on nape and back.
Mingyue ZHANG ; Wanghaonan CHEN ; Feihong SHU ; Ye LIU ; Kerong TAO ; Chi ZHANG ; Xing YOU ; Guangfeng SUN
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(9):1133-1137
OBJECTIVE:
To explore the effectiveness of hairpin shaped incision combined with cover-lifting flap in plastic surgery of huge fat pad on nape and back.
METHODS:
Between March 2019 and March 2023, 10 patients with huge fat pad on the nape and back were treated. There was 1 male and 9 females with an average age of 52 years (range, 39-57 years). All patients had soft tissue bulge on the nape and back. Preoperative MRI showed the subcutaneous fat thickening. The length of the longitudinal axis of the fat pad ranged from 10.0 to 25.0 cm (mean, 14.1 cm), the length of the transverse axis ranged from 6.0 to 15.0 cm (mean, 10.8 cm); the thickness of the fat pad ranged from 2.5 to 5.1 cm (mean, 3.9 cm). Under general anesthesia, the patient was placed in a prone position and a hairpin shaped incision was made. The flap was lifted to remove the fat pad according to the marked area. The dressing was changed every 2 days after operation.
RESULTS:
The operation time was 35-110 minutes (mean, 72 minutes). The intraoperative blood loss was 35-80 mL (mean, 49.5 mL). The drainage tube was removed at 2-5 days after operation (mean, 3.4 days). All incisions healed by first intention without incision dehiscence, infection, subcutaneous bruising, hematoma, or other related complications. All patients were followed up 2-24 months (mean, 12 months). All patients had a good shape of the nape and back and no noticeable scar on the incision. According to the Vancouver Scar Scale evaluation criteria, the incision scar score was 3-5 (mean, 3.7) at 2 months after operation. Patients had good neck movement with no recurrence.
CONCLUSION
For the huge fat pad on the nape and back, the plastic surgery using hairpin shaped incision and cover-lifting flap has the advantages of fully exposing the fat pad, concealed incision, simple operation, and natural shape of the nape and back after operation.
Female
;
Humans
;
Male
;
Middle Aged
;
Surgery, Plastic
;
Cicatrix
;
Lifting
;
Plastic Surgery Procedures
;
Surgical Wound
;
Adipose Tissue
10.Efficacy and safety of total aortic arch replacement in elderly patients with Stanford type A aortic dissection
Gang QIAO ; Zhidong ZHANG ; Gangqiang ZOU ; Zhigang SUN ; Zhenfeng HUANG ; Xiaoshan CHEN ; Wei LU ; Jianyang LIU ; Guangfeng LI
Chinese Journal of Geriatrics 2022;41(1):62-65
Objective:To evaluate the efficacy and safety of total aortic arch replacement in elderly patients with Stanford type A aortic dissection(TAAD).Methods:In this retrospective study, a total of 481 TAAD patients treated with total arch replacement in our hospital from January 2016 to January 2020 were divided into three groups: aged≤59 years, 60-69 years and ≥70 years.The differences between three groups in surgical method, extracorporeal circulation time, blocking time, circulatory time, stopping time, surgical time, ventilator use time, ICU time, hospitalization time, treatment rate of continued renal replacement, fatality rate, and cause of death were statistically analyzed and compared.Results:There were statistically significant differences in the stopping time between any two groups of the three groups(all P<0.05). The older the age, the shorter the circulatory arrest time.The difference of ventilator time and ICU time between ≤59 and 60-69 years was statistically significant( P<0.01). Patients with continuous renal replacement(CRRT)were 19.0%(71/373)in ≤59 years, 23.1%(18/78)in 60~69 years, and 26.7%(8/30)over 70 years.In-hospital mortality was 35/373(9.4%)in the group of ≤59 years old, 11/78(14.1%)in the group of 60~69 years old, and 5/30(16.7%)in the group of ≥70 years old.There was no death in patients undergoing type Ⅱ hybrid surgery. Conclusions:Age is one of the important death factors after total aortic arch replacement in TAAD patients.Total aortic arch replacement is an acceptable surgical method for elderly patients with TAAD.Hybridization may reduce hospitalization death in elderly patients.


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