1.Changes in coordination of departments for major epidemic prevention and control in China before and after the outbreak of COVID-19: an analysis on official documents
Zhonghui HE ; Peiwu SHI ; Qunhong SHEN ; Zheng CHEN ; Chuan PU ; Lingzhong XU ; Zhi HU ; Anning MA ; Tianqiang XU ; Panshi WANG ; Hua WANG ; Qingyu ZHOU ; Chengyue LI ; Mo HAO
Shanghai Journal of Preventive Medicine 2025;37(5):446-450
ObjectiveTo analyze the changes in the degree of coordination of China's major epidemic prevention and control efforts before and after the outbreak of the Corona Virus Disease 2019 (COVID-19), so as to explore the impact of epidemic prevention and control measures on coordination dynamics. MethodsA total of 3 864 policy documents related to epidemic prevention and control from January 2000 to December 2020 across 31 provinces (autonomous regions, and municipalities) in China were systematically collected. Contents specific to collaborative and cooperative efforts were extracted, and the extent of interdepartmental coordination were quantified to assess the effectiveness of epidemic prevention and control efforts. Wilcoxon signed-rank test was adopted to statistically analyze the differences between the indicators before and after the epidemic. ResultsThe average overall coordination level for major epidemic prevention and control in 31 provinces (autonomous regions, and municipalities) increased from 43.06% to 97.62%, and the average coordination levels in the eastern, central, and western China soared from 42.29%, 37.50%, and 47.46%, to 98.81%, 96.20%, and 97.46%, respectively, with statistically significant differences (all P<0.05). In terms of department categorization, coordination levels in the professional departments and the key support departments peaked at 100.00%, while other support departments rose to 95.43%, with an increase of 77.15%, 181.85%, and 139.89%, respectively, exhibiting noteworthy statistically significant differences (all P<0.001). ConclusionThe scope of coordination departments of China’s major epidemic prevention and control exists a remarkable surge following the COVID-19 outbreak, notable heightened coordination is particularly observed among the key support departments. Future endeavors should prioritize the roles played by diverse departments in epidemic prevention and control, enhancing both the clarity of departmental responsibilities and the effectiveness of interdepartmental coordination.
2.A systematic evaluation of the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces
Huayi ZHANG ; Qingyu ZHOU ; Huihui HUANGFU ; Peiwu SHI ; Qunhong SHEN ; Chaoyang ZHANG ; Zheng CHEN ; Chuan PU ; Lingzhong XU ; Anning MA ; Zhaohui GONG ; Tianqiang XU ; Panshi WANG ; Hua WANG ; Chao HAO ; Zhi HU ; Chengyue LI ; Mo HAO
Shanghai Journal of Preventive Medicine 2025;37(5):451-457
ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.
3.lague epidemiology in plague focus of wild rodents in Yunnan Province, 2017-2023
SHI Qingxi ; PU Ennian ; SU Liqiong
China Tropical Medicine 2025;25(1):36-
Objective To analyze the epidemic characteristics of plague epidemics, host and vector community structure, and abundance in plague focus of wild rodents in Yunnan Province, 2017-2023, providing a scientific basis for formulating plague prevention strategies and forecasting warning for this epidemic foci. Methods Following the requirements of the "National Plague Surveillance Plan" and the "Yunnan Provincial Plague Surveillance Plan", host-vector surveillance, etiology, and serological testing were carried out, and plague epidemic data and host-vector surveillance data in plague focus of wild rodents in Yunnan Province, 2017-2023 were collected and sorted using Excel 2019 software to create a database for descriptive analysis. Results From 2017 to 2023, 11 animal plague epidemics were discovered in the wild plague foci of Yunnan Province, with 18 epidemic spots. From the altitude distribution point of view, 7 epidemic spots were distributed at an altitude of 2 800-3 000 meters, another seven at 3 000 and 3 200 meters, and four spots were located in areas with an altitude of ≥3 200 meters; a total of 36 samples of host and vector animals were detected positive, including 28 positive samples of host animals and 8 positive samples of vector animals, and 29 strains of Yersinia pestis were isolated; in terms of species composition, Eothenomys miletus accounted for the largest proportion of 41.67%, followed by Apodemus chevrieri at 22.22%; Ctenophthalmus quadratus at 11.11%; Rattus tanezumi and Neopsylla specialis each at 8.33%, and Dremomys pernyi, rat carcass, and Frontopsyllas padix each accounted for 2.78%; the epidemic peaked in April, and no human cases were found. A total of 453 220 rat cages (traps) were placed, capturing 27 677 rodents, with an average capture rate of 6.11%. A total of 25 075 main hosts, Apodemus chevrieri and Eothenomys miletus, were captured, accounting for 90.60% of the total capture rate. A total of 14 700 fleas were seized on the surface of small animals, with a total flea infection rate of 23.13% and a flea index of 0.59. The main vectors were Ctenophthalmus quadratus and Neopsylla specialis, with constituting ratios of 45.71% and 22.69%, respectively. Conclusions From 2017 to 2023, the population density of main host animals in Yunnan's wild rodent plague foci was relatively high and showed an upward trend, possibly related to the local planting structures. Plague plays a regulatory role in host population structures. Epidemics among animals showed obvious seasonality, with a trend of expanding epidemic areas. No human cases were found, but Yersinia pestis was detected in Rattus tanezumi in human settlements, raising the possibility that animal plague could spread to humans. It suggests strengthening the monitoring of areas adjacent to the epidemic source, eradicating rats and fleas in spring, improving the accuracy of plague prediction and early warning, providing strong technical support for the early detection of plague among animals, and preventing the spread of the epidemic to humans.
4.Cloning and Transcriptional Activity Analysis of Endogenous U6 Promoters in Artemisia annua
Yuting PU ; Bohan CHENG ; Mengyue WANG ; Jun ZOU ; Ranran GAO ; Lan WU ; Qinggang YIN ; Li XIANG ; Yuhua SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):161-167
ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9(CRISPR/Cas9)gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity, which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system, which holds significant importance for its molecular breeding. MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana, endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase (LUC) reporter gene, and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay. ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements, upstream sequence element (USE) and TATA-box, which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3, AaU6-1, and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter, with AaU6-3 exhibiting the highest activity. ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua, providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.
5.Early effectiveness of navigation-free robot-assisted total knee arthroplasty in treating knee osteoarthritis with extra-articular deformities.
Chen MENG ; Yongqing XU ; Rongmao SHI ; Luqiao PU ; Jian'an JI ; Xingyou YAO ; Xizong ZHOU ; Chuan LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):5-12
OBJECTIVE:
To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities.
METHODS:
The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score.
RESULTS:
There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05).
CONCLUSION
Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans
;
Arthroplasty, Replacement, Knee/methods*
;
Osteoarthritis, Knee/surgery*
;
Robotic Surgical Procedures/methods*
;
Male
;
Female
;
Retrospective Studies
;
Range of Motion, Articular
;
Middle Aged
;
Aged
;
Treatment Outcome
;
Osteotomy/methods*
;
Knee Joint/physiopathology*
;
Operative Time
6.Effectiveness of three-dimensional-printed microporous titanium prostheses combined with flap implantation in treatment of large segmental infectious bone defects in limbs.
Yongqing XU ; Xinyu FAN ; Teng WANG ; Shaoquan PU ; Xingbo CAI ; Xiangwen SHI ; Wei LIN ; Xi YANG ; Jian LI ; Min LIU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):521-528
OBJECTIVE:
To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs.
METHODS:
A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score.
RESULTS:
All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76).
CONCLUSION
The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans
;
Male
;
Female
;
Middle Aged
;
Printing, Three-Dimensional
;
Titanium
;
Retrospective Studies
;
Surgical Flaps
;
Adult
;
Prosthesis Implantation/methods*
;
Plastic Surgery Procedures/methods*
;
Treatment Outcome
;
Prostheses and Implants
;
Bone Diseases, Infectious/surgery*
;
Extremities/surgery*
;
Prosthesis Design
7.Clinical efficacy of autologous apheresis platelet-rich plasma combined with adjustable titanium plate fixation in the treatment of Rockwood type Ⅲ acromioclavicular joint dislocation.
Wei CAI ; An-Ping WU ; Hai-Tao TAN ; Gao-Bing XU ; Zhuo-Yi FU ; Yong PENG ; Di-Shi GUI ; Qiao-Mei PU
China Journal of Orthopaedics and Traumatology 2025;38(6):587-593
OBJECTIVE:
To explore clinical efficacy of autologous platelet-rich plasma(PRP) in treating Rockwood type Ⅲ acromioclavicular dislocation.
METHODS:
From January 2019 to July 2021, 32 patients with Rockwood type Ⅲ acromioclavicular dislocation were treated with minimally invasive adjustable titanium plate internal fixation, and were divided into PRP group and control group according to whether PRP treatment was performed, with 16 patients in each group. In PRP group, there were 10 males and 6 females, aged from 28 to 47 years old with an average of (36.75±7.14) years old;the time from injury to surgery ranged from 1 to 31 h with an average of (26.13±3.98) h;5 patients on the left side and 11 patients on the right side;PRP was injected once during operation and the 4th and 8th weeks after operation respectively. In control group, there were 8 males and 8 females, aged from 30 to 52 years old with an average of (38.50±5.48) years old; the time from injury to surgery ranged from 1 to 29 h with an average of (25.48±3.11) h;7 patients on the left side and 9 patients on the right side; minimally invasive surgical treatment was performed. Visual analogue scale(VAS) was used to evaluate pain and Constant-Murley score for shoulder joint function was used to evaluate the recovery of shoulder joint movement function before operation and 1, 3, 6, and 12 months after operation respectively.
RESULTS:
All patients were followed up for 12 to 28 months with an average of (18.3±5.2) months. All incisions patients healed well without adverse events such as infection. Postoperative VAS of PRP group at 1, 3, and 6 months were (5.5±1.2), (3.7±1.6), and (2.4±1.2), respectively, while were lower than those of control group (6.6±1.4), (4.9±1.1), and (3.7±1.3), respectively;and had statistical differences between two groups (P<0.05). There was no statistically significant difference in VAS between two groups before operation and 12 months after operation (P>0.05). Postoperative Constant-Murley scores of PRP group at 1, 3, and 6 months were (64.09±11.61), (73.19±12.89), and (82.61±14.81) points, respectively, which were higher than those of control group were (52.32±17.42), (61.65±14.43), and (72.52±11.04) respectively;and the differences were statistically significant (P<0.05). There was no statistically significant difference in Constant-Murley scores at 12 months after operation between two groups (P>0.05). In PRP group, there was no statistically significant difference at 6 months and 12 months after operation (P>0.05), while there were statistically significant differences at the other time points (1 month after operation compared with before operation, 3 months after operation compared with 6 months after operation, and 3 months after operation compared with 1 month after operation) (P<0.05). In control group, there was no statistically significant difference when comparing 1 month and 3 months after operation (P>0.05), while at the other time points (1 month after operation with before operation, 3 months after operation with 6 months after operation, and 6 months after operation with 12 months after operation), the differences were all statistically significant (P<0.05).
CONCLUSION
Adjustable titanium plate fixation combined with postoperative injection of PRP for the treatment of Rockwood type III acromioclavicular joint dislocation has effect of promoting the recovery of shoulder joint function and reducing pain.
Humans
;
Male
;
Female
;
Adult
;
Middle Aged
;
Platelet-Rich Plasma
;
Acromioclavicular Joint/surgery*
;
Bone Plates
;
Titanium
;
Joint Dislocations/therapy*
;
Fracture Fixation, Internal/methods*
8.Meta analysis of effects of healthy eating patterns on mortality,ESKD and CVD incidence in patients with CKD
Yang LI ; Hongmei PENG ; Xia HUANG ; Shi PU ; Xiangchun TANG ; Yu SHI
Chongqing Medicine 2024;53(2):264-269
Objective To investigate the impact of healthy eating patterns on the mortality rate and in-cidence rates of end-stage kidney disease(ESKD)and cardiovascular disease(CVD)in the patients with chronic kidney disease(CKD)by meta analysis.Methods The studies on the relationship between the dietary patterns on the mortality,and the incidence rates of ESKD and CVD in the patients with CKD were retrieved from PubMed,Embase,Cochrane Library,CNKI,Wanfang Database and VIP Database.The retrieval time was from the database establishment to January 2023.The two researchers independently screened the literatures,ex-tracted the data and conducted the literature quality evaluation.The RevMan5.3 software was used for the meta-analysis of the included literatures.Results A total of 10 studies were included in this study,involving 27 291 patients.The results showed that the mortality(HR=0.70,95%CI:0.57-0.87,Z=3.18,P=0.001)and the ESKD incidence rate(HR=0.80,95%CI:0.71-0.91,Z=3.44,P<0.001)and CVD inci-dence rate(HR=0.77;95%CI:0.61-0.97,Z=2.21,P=0.003)had statistical differences between the pa-tients with high dietary score and the patients with low dietary score.Conclusion Persisting in the healthy dieta-ry patterns could decrease the mortality rate,and incidence rates of ESKD and CVD in the patients with CKD.
9.Comparison of clinical outcome between the percutaneous pedicle screw fixation and Wiltse approach for the treatment of thoracolumbar fractures without neurological injury
Mengmeng CHEN ; Pu JIA ; Hao CHEN ; Li BAO ; Guan SHI ; Fei FENG ; Shuangjiang ZHANG ; Hai TANG
International Journal of Surgery 2024;51(3):159-165
Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.
10.Growth differentiation factor-5 modified by bisphosphonate promotes osteogenic differentiation of MC3T3-E1 cells
Lisi LI ; Chengdong ZHANG ; Xiaolong LI ; Ziyu YE ; Chao PU ; Zaijun YANG ; Feng SHI ; Dongqin XIAO
Chinese Journal of Tissue Engineering Research 2024;28(3):373-379
BACKGROUND:As a member of bone morphogenetic proteins,growth differentiation factor-5 shows promising potential in the application of cartilage and bone repair.The affinity of growth differentiation factor-5 onto bone tissue determines protein use efficiency,so it is of great significance to prepare growth differentiation factor-5 with bone targeting capability. OBJECTIVE:To modify growth differentiation factor-5 using bisphosphonates and investigate the effects of modified protein on the growth of preosteoblasts in mice. METHODS:Pamidronate disodium/growth differentiation factor-5 complex was prepared using chemical crosslinking to couple growth differentiation factor-5 with pamidronate disodium.The functional groups and structures of the complex were characterized using Fourier transform infrared spectroscopy and circular dichromatography.To determine the bone targeting in vitro,the binding of the modified growth differentiation factor-5 with calcium phosphate and in vitro release amount of growth differentiation factor-5 were measured with an ELISA kit.Growth differentiation factor-5(control group)and the pamidronate disodium/growth differentiation factor-5 complex(experimental group)were co-cultured with preosteoblasts MC3T3-E1.Individually cultured cells were blank controls.The effect of the complex on cell proliferation and differentiation was evaluated. RESULTS AND CONCLUSION:(1)The infrared spectroscopy and circular dichromatography results indicated that the bisphosphonate/growth differentiation factor-5 complex was successfully prepared without significant changes in the protein secondary structure.In vitro protein adsorption results showed that growth differentiation factor-5 adsorption on calcium phosphate was increased by about one time after coupling with a bisphosphonate.In the presence of cysteine,growth differentiation factor-5 could be released from the bisphosphonate/growth differentiation factor-5 complex.(2)CCK-8 assay results showed that the absorbance value of the experimental group cultured for 4 and 7 days was higher than that of the control group and blank control group(P<0.000 1).After 7 days of culture,the expression of alkaline phosphatase in the experimental group was significantly higher than that in the control group and blank control group(P<0.000 1).After 13 days of culture,the content of calcium nodules in the experimental group was significantly higher than that in the control group and the blank control group(P<0.000 1).The results of qRT-PCR showed that the mRNA expression of alkaline phosphatase,osteocalcin and Runx2 in the experimental group was higher than that in the control group and the blank control group after 7 days of culture(P<0.01,P<0.001,P<0.000 1).(3)These findings exhibit that bisphosphonate modification can enhance the binding capacity of growth differentiation factor-5 to calcium phosphate as well as improve its biological activity.

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