1.Docetaxel for 15 patients with paclitaxel-resistant advanced non-small cell lung cancer
Yifei ZHANG ; Yunhua XU ; Xiangyun YE ; Ziming LI ; Linping GU ; Shun LU
Cancer Research and Clinic 2009;21(7):458-460
Objective To determine the efficacy and toxicity of docetaxel in patients with paclitaxel-resistant advanced non-small cell lung cancer (NSCLC). Methods The clinical data from 15 patients with NSCLC who were admitted in the Shanghai Chest Hospital from January 2005 to May 2008 were retrospectively analyzed. The effects and toxicities of the second-line treatment were assessed. The progression-free survival time(PFS) and overall survival time(OS) were analyzed. Results The disease control rate was 66.7 %, with a progression-free survival time of 6 months, and a overall survival time of 17.3 months. The 1-year survival rate was 63.3 %. The toxic effects were as expected. Conclusion The doeetaxel-based agent is active in patients with paelitaxel-resistant advanced NSCLC.
2.Evaluation of clinical prognosis of liver transplant recipients of hepatocellular carcinoma complicated with microvascular invasion
Ziming LIANG ; Linsen YE ; Hui TANG ; Laien SONG ; Shijie GU ; Shuhong YI
Organ Transplantation 2020;11(3):350-
Objective To investigate the clinical prognosis of the liver transplant recipients diagnosed with hepatocellular carcinoma (HCC) complicated with microvascular invasion (MVI). Methods Clinical data of 3 447 HCC recipients undergoing liver transplantation were extracted from Surveillance, Epidemiology, and End Results (SEER) database of American National Cancer Institute. According to the incidence of MVI, all recipients were divided into MVI (
3.Clinical outcome of arthroscopic anatomic single bundle reconstruction of posterior cruciate ligament assisted by internal tension relieving technique combined with rapid rehabilitation in the treatment of posterior cruciate ligament rupture
Yang YU ; Zhenglyu ZHAO ; Bing XIE ; Zhengliang SHI ; Guoliang WANG ; Bohan XIONG ; Ziming GU ; Jinrui LIU ; Yanlin LI
Chinese Journal of Trauma 2023;39(7):593-602
Objective:To compare the clinical efficacies between arthroscopic anatomic single bundle reconstruction of posterior cruciate ligament (PCL) assisted by internal tension relieving technique combined with rapid rehabilitation and anatomic single bundle reconstruction combined with conventional rehabilitation in the treatment of PCL rupture.Methods:A retrospective cohort study was used to analyze the clinical data of 88 patients with PCL rupture admitted to First Affiliated Hospital of Kunming Medical University from September 2016 to September 2020. The patients included 65 males and 23 females, aged 18-55 years [(39.3±10.8)years]. Forty-four patients underwent arthroscopic anatomic single bundle reconstruction of PCL assisted by internal tension relieving technique combined with rapid rehabilitation therapy (tension-relieving group), and 44 patients underwent arthroscopic routine anatomic single bundle reconstruction of PCL combined with conventional rehabilitation (traditional group). The two groups were compared before and at 3, 12, and 24 months after surgery regarding the following items: International Knee Literature Committee (IKDC) score, Hospital for Special Surgery (HSS) score, Lysholm score, knee motion cycle (maximum stride length, minimum stride length, and stride frequency) and 6 kinematic indicators (angle of forward and back extension, angle of internal and external rotation, angle of internal and external rotation, up and down displacement, internal and external displacement, and forward and back displacement). The Marburger arthroscopy score (MAS) and Professor Ao Yingfang′s improved score by secondary arthroscopy were compared between the two groups at 12 months after surgery. The perioperative complications were observed.Results:All patients were followed for 24-36 months [(25.5±6.3)months]. In tension-relieving group and the traditional group, the values of IKDC score were (71.8±9.8)points and (68.5±6.5)points at 3 months after surgery, (87.6±6.0)points and (87.6±5.5)points at 12 months after surgery, and (95.5±3.1)points and (92.8±11.6)points at 24 months after surgery, respectively. The values were gradually increased, significantly higher than those before surgery [(48.1±16.9)points and (47.1±15.0)points] (all P<0.05). There were no significant differences between the two groups at each time point (all P>0.05). In tension-relieving group and the traditional group, the values of HSS score were (74.2±6.2)points and (68.4±9.5)points at 3 months after surgery, (91.9±5.4)points and (88.4±4.7)points at 12 months after surgery, and (97.1±2.0)points and (96.2±2.8)points at 24 months after surgery, respectively. The values of HSS score gradually increased, significantly higher than those before surgery [(57.5±17.7)points and (56.8±14.3)points] (all P<0.05). At 3 and 12 months after surgery, the values of HSS score in the tension-relieving group were significantly higher than those in the traditional group (all P<0.05), but others were not significantly different between the two groups (all P>0.05). In tension-relieving group and the traditional group, the values of Lysholm score were (74.2±14.9)points and (70.3±7.5)points at 3 months after surgery, (90.9±6.1)points and (88.7±4.7)points at 12 months after surgery, and (96.9±3.0)points and (96.3±2.8)points at 24 months after surgery, respectively. The values of Lysholm score were gradually increased, significantly higher than those before operation [(48.7±20.7)points and (48.2±19.9)points] (all P<0.05). There were no significant differences between the two groups at any time points (all P>0.05). At 3, 12, and 24 months after surgery, the motion cycle (maximum stride length, minimum stride length and stride frequency) and 6 kinematic indicators (angle of forward bending and backward extension, angle of internal and external rotation, angle of internal and external rotation, internal and external displacement, up and down displacement, and forward and backward displacement) of knee joint were significantly improved in both groups compared with those before surgery (all P<0.05). At 3, 12, and 24 months after surgery, the forward and backward displacement in the tension-relieving group was significantly decreased than that in the traditional group (all P<0.05), but others were not significantly different between the two groups (all P>0.05). The MAS was rated as excellent to good in 14 patients and fair to poor in 2, with the excellent and good rate of 87.5% (14/16) in the tension-relieving group, while the score was rated as excellent to good in 11 patients and fair to poor in 3, with the excellent and good rate of 78.6% (11/14) in the traditional group ( P>0.05). The Professor Ao Yingfang′s improved score was (10.6±1.5)points in the tension-relieving group, markedly higher than that in the traditional group [(9.6±2.3)points] ( P<0.05). No perioperative complications were observed. Conclusion:Compared with anatomic single bundle reconstruction combined with conventional rehabilitation, arthroscopic anatomic single bundle reconstruction of PCL assisted by internal tension relieving technique combined with rapid rehabilitation have higher subjective function score, better anteroposteric stability during knee movement, and better results of secondary microscopy.
4.Prevalence of dyslipidemia in subjects with type 2 diabetes mellitus in Beijing urban communities:Beijing community diabetes study 8
Guangran YANG ; Shenyuan YUAN ; Hanjing FU ; Gang WAN ; Liangxiang ZHU ; Mingxia YUAN ; Sufang PAN ; Xianglei BU ; Jiandong ZHANG ; Xueping DU ; Yuling LI ; Yu JI ; Xiaoning GU ; Yue LI ; Xueli CUI ; Wei BAI ; Yujie CHEN ; Ziming WANG ; Shuyan CHENG ; Ying GAO ; Deyuan LIU ; Yipin WANG
Chinese Journal of General Practitioners 2012;(10):748-752
Objective To investigate the prevalence of dyslipidemia in subjects with type 2 diabetes mellitus in Beijing urban communities.Methods Total 3316 subjects with type 2 diabetes (age 20-80 years) were recruited from 15 urban community health centers in Beijing using a multi-stage random sampling approach.Dyslipidemia was diagnosed according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults:2007 version.Results Among 3316 diabetic subjects (1329 malesand 1987 females),75.6% (2506/3316) had dyslipidemia,the prevalence was 72.5% (964/1329)in men and 77.6% (1542/1987) in women.The prevalence of hypertriglyceridemia and hypercholesterolemia was 41.9% (1388/3316) and 48.1% (1595/3316),respectively.31.5% (1043/3316) subjects had high levels of low-density lipoprotein cholesterol (LDL-C) and 21.2% (703/3316) had low high-density lipoprotein cholesterol (HDL-C).Among all subjects with dyslipidemia only 22.9% (575/2506) took hypolipid agents.The overall blood lipid control rates of triglyceride (TG),total cholesterol (TC),LDL-C and HDL-C in 1393 subjects with dyslipidemia history were 48.0% (669/1393),17.4% (242/1393),30.9% (430/1393) and 75.8% (1056/1393),respectively.Diabetics with dyslipidemia had higher body mass index,waist circumference,blood pressure,plasma glucose and hemoglobin A1c.The prevalence of dyslipidemia in the overweight and uncontrolled-glucose group were 79.0% (1678/2125),78.9% (1756/2227),respectively.Logistic regression analysis showed that gender,age,body mass index and hemoglobin A1c were associated with dyslipidemia.Conclusions The prevalence of dyslipidemia in diabetic subjects in Beijing urban communities is high and less than one quarter patients take hypolipid agents.Age,body mass index and hemoglobin A1c are the risk factors of dyslipidemia in type 2 diabetic patients.
5.Current status of hypoglycemic drug use among 3297 adult patients with type 2 diabetes in 15 urban communities of Beijing:Beiiing Community Diabetes Study-7
Bin LI ; Hanjing FU ; Shenyuan YUAN ; Liangxiang ZHU ; Jinkui YANG ; Gang WAN ; Sufang PAN ; Mei YU ; Xianglei PU ; Jiandong ZHANG ; Xueping DU ; Yuling LI ; Yu JI ; Xiaoning GU ; Yue LI ; Xueli CUI ; Wei BAI ; Yujie CHEN ; Ziming WANG ; Qingsheng ZHU ; Ying GAO ; Deyuan LIU ; Yipin WANG
Chinese Journal of General Practitioners 2011;10(11):796-800
Objective To investigate current status of use of oral hypoglycemic drugs and insulin among adult patients with type 2 diabetes mellitus (T2DM) in urban community of Beijing.Methods In total,3297 T2DM patients aged more than 20 years from 15 urban communities of Beijing were studied.Their body weight,height,fasting plasma glucose level and glycosylated hemoglobin Alc (HbAlc) were measured.A door-to-door questionnaire survey on use of oral hypoglycemic drugs and insulin was conducted for them.All the T2DM patients surveyed were divided into four groups based on their received intervention.Results ①Of 3279 T2DM patients,454 (13.8%) received lifestyle intervention,971 (29.5%) used only one oral hypoglycemic drug,1179 (35.7%) with combined oral hypoglycemic drugs,and 693(21.0%) with insulin.②There was significant difference in average HbAlc among the four groups of T2DM patients with lifestyle intervention,only one oral hypoglycemic drug,combined oral hypoglycemic drugs,and insulin,with HbAI c of (7.0 ± 1.9) %,(7.1 ± 1.5) %,(7.4 ± 1.5 ) %,and (7.5 ± 1.5 ) %for them,respectively ( F =15.1,P < 0.01 ).Proportions of the T2DM patients with HbAlc equal to or higher than 7.0% were 32.2%,39.4%,52.1% and 59.5% for the four groups,respectively ( x2 =117.7,P < 0.01 ).③In the T2DM patients with lifestyle intervention,32.2% (146/454) of them with HbA1 c equal to or higher than 7.0% were untreated with any oral hypoglycemic drug.In those with only one oral hypoglycemic drug,39.4% (383/971) of them with HbAlc equal to or higher than 7.0% were not treated with combined oral hypoglycemic drugs and/or insulin.In those with combined oral hypoglycemic drugs,52.1% (614/1079) of them with HbAlc equal to or higher than 7.0% were not received combined insulin treatment.④ Fasting plasma glucose level,treatment strategies,postprandial 2-h blood glucose level and length of the illness were independent risk factors for HbAlc level equal to or higher than 7.0%,with odds ratio (OR) of 1.757,1.256,1.175 and 1.031,respectively.⑤ In 2843 T2DM patients with oral hypoglycemie drugs and/or insulin treatment,1494 (52.6% ) received biguanides and 693 received (24.4% )insulin,respectively.Conclusions More than half of adult patients with T2DM do not meet the target of glycemic control of HbAlc less than 7.0% in urban communities of Beijing,due to not active use of oral hypoglycemic drugs,and not timely adoption of combined use of oral hypoglycemic drugs and insulin therapy.
6.Clinical characteristics of diabetic patients with metabolic syndrome and its components at 15 urban communities in Beijing
Hanjing FU ; Shenyuan YUAN ; Gang WAN ; Liangxiang ZHU ; Mingxia YUAN ; Guangran YANG ; Sufang PAN ; Xianglei BU ; Jiandong ZHANG ; Xueping DU ; Yuling LI ; Yu JI ; Xiaoning GU ; Yue LI ; Xueli CUI ; Wei BAI ; Yujie CHEN ; Ziming WANG ; Qingsheng ZHU ; Ying GAO ; Deyuan LIU ; Yuntao JI ; Ze YANG
Chinese Journal of General Practitioners 2011;10(6):390-393
Objective To study clinical characteristics of type 2 diabetic(T2D)patients with metabolic syndrome(MS)and its components in Beijing urban communities.Methods Totally,3295 T2D patients involved in a combined prospective diabetic management study from 15 urban communities in Beijing were classified as four groups, according to 2004 Chinese Diabetes Society's definition of MS, i. e, isolated T2D, T2D with one component of MS, T2D with two components of MS and T2D with three components of MS. Their clinical characteristics were analyzed. Results ( 1 ) Among 3295 T2D patients, 155 (4. 7% )were isolated T2D, 107 (32.6%) T2D with one component of MS, 1386 (42.1%) T2D with two components of MS and 679 (20.6%) T2D with three components of MS, with an overall 62.7% (2065/3295) of T2D patients complicated with MS. (2) In these T2D patients, the more components of MS they had, the higher body mass index (BMI), waist circumference, waist to hip circumference ratio (WHR),systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting serum levels of insulin and triglyceride (TG) and the lower level of high-density lipoprotein-cholesterol (HDL) were presented (P <0. 01 ). (3) Percentage of isolated T2D in women increased from 49. 0% (76/155) to 61.9% (420/679)of those with three components of MS ( P < 0 01 ), with increasing of components of MS. (4) Multiple logistic regression analysis showed that BMI, history of hypertension, decreased HDL, increased TG,increased blood pressure, all were risk factors for T2D patients complicated with MS. Conclusions Among T2D patients in urban communities of Beijing, 95.3% (3140/3295) of them complicated with one or more components of MS, and 61.9% (420/679) of them complicated with MS. So, community diabetic management must be implemented in an all-round way, including control of blood pressure, blood lipids,body weight and so on, in addition to control of blood sugar.
7.Constructing a model of anterior cruciate ligament reconstruction with autologous Achilles tendon in southern Yunnan small-ear pigs
Bohan XIONG ; Yang YU ; Liling ZHENG ; Tengyun YANG ; Xiaojun LU ; Xu WANG ; Kaiwei LI ; Hong YU ; Yajuan LI ; Kaiyan DONG ; Yaozhang ZHANG ; Jinrui LIU ; Ziming GU ; Bigeng HU ; Yanlin LI
Chinese Journal of Tissue Engineering Research 2024;28(20):3157-3163
BACKGROUND:As a dominant breed pig in southwest China,the southern Yunnan small-ear pig has been widely used as an experimental animal in the basic research of other disciplines,but there are still no reports on its application in anterior cruciate ligament reconstruction. OBJECTIVE:To establish a large animal model of the southern Yunnan small-ear pig with anterior cruciate ligament with autologous Achilles tendon was established. METHODS:Twenty adult female Yunnan small-ear pigs were equally randomized into two groups.In the autologous Achilles tendon group,the right knee anterior cruciate ligament was reconstructed with autologous Achilles tendon as a graft,while in the sham-operated group,a similar operation was performed on the right knee without any treatment of the anterior cruciate ligament.General conditions of each pig were observed and recorded before and 12 months after surgery.Ligaments and grafts were taken for gross observation and MAS scoring.Hematoxylin-eosin staining was performed to observe morphological characteristics of ligaments.The staining and arrangement of type I and type Ⅲ collagen were evaluated by immunohistochemistry.Transmission electron microscopy was used to observe the type,size,diameter,ratio,and distribution of collagen fibers in ligaments. RESULTS AND CONCLUSION:All animals had normal diet and activity,good wound healing,no obvious inflammatory reaction,no local purulent infection,and no significant changes in mental and urinary conditions compared with those before surgery.The reconstructed cruciate ligament of the knee was intact,with no stiffness and normal range of motion.Both the anterior drawer and Lachman tests were negative.Gross observation of the graft:12 months after surgery,the grafts was in good position,with good integrity,obvious tension,ligament color close to the original anterior cruciate ligament,and complete surface synovial coverage.Most of the intraarticular ligaments in the autologous Achilles tendon group were defined as MAS I type and a few were defined as MAS Ⅱ type.In the sham-operated group,the intraarticular ligament was defined as MAS I type.Hematoxylin-eosin staining indicated that,12 months after surgery,collagen fibers in the autologous Achilles tendon group began to appear bundled,isotropic,and uniformly arranged,with more obvious isotropic corrugations,and the nuclei were mainly linear or spindle-shaped,which were similar to those in normal anterior cruciate ligament tissue of the sham-operated group.Immunohistochemistry results indicated that,12 months after surgery,there was a higher expression of type I collagen and significantly less expression of type Ⅲ collagen in the reconstructed anterior cruciate ligament in the autologous Achilles tendon group.The degree of type I and type Ⅲ staining was similar in the two groups.Under the transmission electron microscope,the diameter,arrangement and density of collagen fibers in the reconstructed anterior cruciate ligament of the autologous Achilles tendon group were similar to those of the original anterior cruciate ligament at 12 months after surgery,indicating that the ligament remodeling process had been basically completed in the autologous Achilles tendon group at 12 months after surgery.Through a comprehensive evaluation of animal general conditions,ligament general view,MAS score,hematoxylin-eosin staining,immunohistochemistry,and transmission electron microscopy observation,we successfully established a large animal model of anterior cruciate ligament reconstruction using autogenous Achilles tendon in southern Yunnan small-ear pigs,with good morphological,histological and ultrastructural results.
8.Three-dimensional kinematic analysis of knee joint after anterior cruciate ligament reconstruction with personalized femoral positioner based on apex of deep cartilage.
Renjie HE ; Ziwen NING ; Zhengliang SHI ; Ziming GU ; Yanlin LI ; Guoliang WANG ; Chuan HE
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(6):663-669
OBJECTIVE:
To investigate the changes of knee joint kinematics after anterior cruciate ligament (ACL) reconstruction assisted by personalized femoral positioner based on the apex of deep cartilage (ADC).
METHODS:
Between January 2021 and January 2022, a total of 40 patients with initial ACL rupture who met the selection criteria were randomly divided into the study group (using the personalized femoral positioner based on ADC design to assist ACL reconstruction) and the control group (not using the personalized femoral positioner to assist ACL reconstruction), with 20 patients in each group. Another 20 volunteers with normal knee were collected as a healthy group. There was no significant difference in gender, age, body mass index, and affected side between groups ( P>0.05). Gait analysis was performed at 3, 6, and 12 months after operation using Opti _ Knee three-dimensional knee joint motion measurement and analysis system, and the 6 degrees of freedom (flexion and extension angle, varus and valgus angle, internal and external rotation angle, anteroposterior displacement, superior and inferior displacement, internal and external displacement) and motion cycle (maximum step length, minimum step length, and step frequency) of the knee joint were recorded. The patients' data was compared to the data of healthy group.
RESULTS:
In the healthy group, the flexion and extension angle was (57.80±3.45)°, the varus and valgus angle was (10.54±1.05)°, the internal and external rotation angle was (13.02±1.66)°, and the anteroposterior displacement was (1.44±0.39) cm, the superior and inferior displacement was (0.86±0.20) cm, and the internal and external displacement was (1.38±0.39) cm. The maximum step length was (51.24±1.29) cm, the minimum step length was (45.69±2.28) cm, and the step frequency was (12.45±0.47) step/minute. Compared with the healthy group, the flexion and extension angles and internal and external rotation angles of the patients in the study group and the control group decreased at 3 months after operation, and the flexion and extension angles of the patients in the control group decreased at 6 months after operation, and the differences were significant ( P<0.05); there was no significant difference in the other time points and other indicators when compared with healthy group ( P>0.05). In the study group, the flexion and extension angles and internal and external rotation angles at 6 and 12 months after operation were significantly greater than those at 3 months after operation ( P<0.05), while there was no significant difference in the other indicators at other time points ( P>0.05). There was a significant difference in flexion and extension angle between the study group and the control group at 6 months after operation ( P<0.05), but there was no significant difference of the indicators between the two groups at other time points ( P>0.05).
CONCLUSION
Compared with conventional surgery, ACL reconstruction assisted by personalized femoral positioner based on ADC design can help patients achieve more satisfactory early postoperative kinematic results, and three-dimensional kinematic analysis can more objectively and dynamically evaluate the postoperative recovery of knee joint.
Humans
;
Biomechanical Phenomena
;
Knee Joint/surgery*
;
Femur/surgery*
;
Anterior Cruciate Ligament Injuries/surgery*
;
Range of Motion, Articular
;
Cartilage/surgery*
;
Anterior Cruciate Ligament Reconstruction/methods*
9.Effectiveness of anterior cruciate ligament reconstruction with personalized femoral locator based on apex of deep cartilage.
Renjie HE ; Ziwen NING ; Ziming GU ; Zhengliang SHI ; Yaoyu XIANG ; Guoliang WANG ; Yanlin LI ; Chuan HE
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(7):833-838
OBJECTIVE:
To investigate the effectiveness of anterior cruciate ligament (ACL) reconstruction assisted by personalized femoral locator based on the apex of deep cartilage (ADC) combined with patient imaging data.
METHODS:
Between January 2021 and January 2022, a total of 40 patients with primary ACL rupture were selected and randomly divided into study group (ACL reconstruction assisted by personalized femoral locator based on ADC) and control group (ACL reconstruction assisted by intraoperative fluoroscopy and traditional femoral locator), with 20 cases in each group. There was no significant difference in gender, age, body mass index, affected side, cause of injury, and preoperative International Knee Documentation Committee (IKDC) score, Lyshlom score, and Tegner score between the two groups ( P>0.05). IKDC score, Lyshlom score, and Tegner score were used to evaluate the functional recovery of the affected knee before operation and at 3, 6, and 12 months after operation. CT scan and three-dimensional reconstruction were performed before and after operation to measure the horizontal distance from ADC to the anterior cartilage margin (L) and the horizontal distance from ADC to the center of the femoral canal (I), and the anteroposterior position of the bone canal (R) was calculated by I/L; the distance from the center to the distal cartilage margin (D) was measured on the two-dimensional cross section; the R value and D value were compared between the two groups.
RESULTS:
The operation time of the study group was significantly less than that of the control group [ MD=-6.90 (-8.78, -5.03), P<0.001]. The incisions of the two groups healed by first intention, and no complication such as intra-articular infection, nerve injury, and deep vein thrombosis of lower limbs occurred. There was no significant difference in the R value and D value between the preoperative simulated positioning and the actual intraoperative positioning in the study group [ MD=0.52 (-2.85, 3.88), P=0.758; MD=0.36 (-0.39, 1.11), P=0.351]. There was no significant difference in the actual intraoperative positioning R value and D value between the study group and the control group [ MD=1.01 (-2.57, 4.58), P=0.573; MD=0.24 (-0.34, 0.82), P=0.411]. The patients in both groups were followed up 12-13 months (mean, 12.4 months). The IKDC score, Lysholm score, and Tegner score of the two groups increased gradually with time, and there were significant differences between pre- and post-operation ( P<0.05). There was no significant difference in the scores between the two groups at each time point after operation ( P>0.05).
CONCLUSION
The personalized femoral locator based on ADC can accurately assist the femoral tunnel positioning in ACL reconstruction, which can shorten the operation time when compared with traditional surgical methods, and achieve satisfactory early effectiveness.
Humans
;
Anterior Cruciate Ligament Injuries/surgery*
;
Anterior Cruciate Ligament Reconstruction/methods*
;
Cartilage/surgery*
;
Knee Joint/surgery*
;
Treatment Outcome
10.Inhibiting collagen I production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles.
Yan YAN ; Cancan DU ; Xixi DUAN ; Xiaohan YAO ; Jiajia WAN ; Ziming JIANG ; Zhongyu QIN ; Wenqing LI ; Longze PAN ; Zhuoyu GU ; Fazhan WANG ; Ming WANG ; Zhihai QIN
Acta Pharmaceutica Sinica B 2022;12(2):939-951
The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.