BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.

OBJECTIVE: To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction. METHODS: Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting. RESULTS: The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin. CONCLUSIONS Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.
Angiotensin II Type 1 Receptor Blockers ; Animals ; Antihypertensive Agents ; Extracellular Matrix Proteins ; metabolism ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering ; Random Allocation ; Telmisartan ; pharmacology ; Transforming Growth Factor beta1 ; pharmacology ; Ureteral Obstruction ; complications ; metabolism

OBJECTIVE: To study the role of JNK (c-Jun N-terminal kinase) signal transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats, to explore whether IL-1β participates the nasal mucosa remodeling in allergic rhinitis by JNK signal transduction pathway. METHOD: Totally 60 male Wistar rats (weighing about 200-250 g)were randomly divided into A (AR group) and B group (control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection ovalbumin and Al(OH)₃. Ovalbumin was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks(A4,A8,or A12 group) each had 10 rats. The rats in B group were sensitized by intraperitoneal injection saline. Saline was respectively dropped in each nasal cavity of every rat for 4,8, 12 weeks(B4, B8, or B12 group), and each had 10 rats. The concentration of IL-1β in serum and nasal lavage fluid were tested by ELASA. The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique. Linear correlation analysis showed the correlation between levels of IL-1β in serum and P-JNK protein, levels of IL-1β in nasal lavage fluid and P-JNK protein. RESULT: The concentrations of IL-1β in serum and nasal lavage fluid of A group were all significantly higher than those of the corresponding B group (all P < 0.01). Compared with A4 group and A8 group, concentrations of IL-1β in nasal lavage fluid of A12 group were significantly increased (all P < 0.01). However the levels of IL-1β in serum were not significantly different among them (all P > 0.05). Mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in corresponding B group (all P < 0.01) and compared with A4 group and A8 group, those of A12 group were significantly increased (all P < 0.01). Strong positive correlation were found between P-JNK and concentration of IL-1β in serum or nasal lavage fluid (r = 0.835 and r = 0.902, all P < 0.01). CONCLUSION JNK signal transduction pathway plays important role in the nasal mucosa remodeling in allergic rhinitis rats. IL-1β participates in AR nasal mucosa remodeling possibly partly through activating JNK signal transduction pathway.
Animals ; Disease Models, Animal ; Interleukin-1beta ; metabolism ; JNK Mitogen-Activated Protein Kinases ; metabolism ; MAP Kinase Signaling System ; Male ; Nasal Mucosa ; pathology ; Ovalbumin ; Paranasal Sinuses ; Rats ; Rats, Wistar ; Rhinitis, Allergic ; metabolism ; pathology ; Signal Transduction

OBJECTIVE: To study the role of P-JNK and P-c-Jun of JNK (c-Jun N-terminal kinase) on nasal mucosa remodeling in allergic rhinitis rats. METHOD: Sixty male Wistar rats (weighing about 200-250 g) were randomly divided into AR group (A group) and B group(control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection of ovalbumin and Al(OH)₃. Rats in group A were randomized into A4, A8 and A12 group (each had 10 rats). Ovalbumin was dropped in each nasal cavity of every rat for 4,8,12 weeks, respectively. Rats in group B were sensitized by saline instead of OVA, and were also divided into B4, B8 and B12 group. Each group had 10 rats. Pathological changes of nasal mucosa in each period were observed by hematoxylin and eosin stain dyeing. The phosphorylation of JNK and c-Jun were tested by immunohistochemistry. RESULT: In A8 group, mucosal congestion and edema thickening with inflammatory cells infiltration of eosinophils were observed in the eighth week, and the inflammatory changes were significantly increased as time went on. The mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in the corresponding B group (all P < 0.01). Moreover, the mean absorbance values of A12 group were significantly higher than A4 group and A8 group (all P < 0.01 ). CONCLUSION The expression of P-JNK and P-c-Jun in the process of nasal mucosa remodeling in allergic rhinitis rats were increased, which suggested that P-JNK and P-c-Jun played important roles in nasal mucosa remodeling of the allergic rhinitis rats.
Airway Remodeling ; Animals ; Disease Models, Animal ; Eosinophils ; cytology ; Injections, Intraperitoneal ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Male ; Nasal Mucosa ; metabolism ; Ovalbumin ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Rhinitis, Allergic ; metabolism ; Signal Transduction

Objective To investigate the efficacy of transorally inserted anvil system(OrVilTM)in esophagogastrostomy and esophagojejunostomy after laparoscopic gastrectomy.Methods The clinical data of 34 patients with gastric neoplasms who were installed OrVilTM for esophagogastrostomy or esophagojejunostomy at the Changhai Hospital from July 2009 to February 2011 were retrospectively analyzed.After radical dissection of lymph nodes and full mobilization of esophagus,the esophagus was transected and the anvil was then transorally inserted into the esophagus by using the OrVilTB system.Double-stapling esophagogastrustomy or esophagojejunostomy with a circular stapler Was performed intracorporeally under direct laparuscopic view.Results The surgery was success fully completed in all the 34 patients with no conversion to open surgery.Two patients had difficulty in placing OrVilTM system.and the condition Was alleviated by reducing tension in the cuff and tilting the head back.The mean operation time,volume of blood loss,duration of postoperative hospital stay and time to gastrointestinal function recovery were 175 minutes(range,90-240 minutes),196 ml(range,50-800 ml),7.6 days(range,5-14 days)and 3 days(range,2-6 days).No postoperative anastomotic leakage Was detected.Thirty-three patients were followed up for 2-20 months with a mean time of(10±6)months,and no tumor recurrence or metastasis occurred.Conclusion OrVilTM system changes insert direction of the anvil,which significantly reduces the difficulty of laparoscopic operation,shortens the operation time and avoids the thoracotomy.

Objective To investigate the efficacy of gastric bypass surgery for the treatment of nonobese type 2 diabetes mellitus. Methods From November 2008 to August 2009, 40 patients with gastric diseases and nonobese type 2 diabetes mellitus were admitted to the Changhai Hospital, and their clinical data were prospectively studied. All patients were randomly divided into 4 groups; 10 patients received Billroth I distal gastrectomy +gastroduodenal anastomosis (BⅠ group) , 10 received proximal gastrectomy + remanant gastric esophageal anastomosis ( PG group), 10 received total gastrectomy + esophagoduodenal Y-anastomosis ( RY group) and 10received subtotal gastrectomy Billroth Ⅱ gastro-jejunostomy (BⅡ group). The length of hospital stay, pre- and postoperative body mass indexes (BMIs) , waist circumferences, levels of fasting blood glucose (FBG) , glycated hemoglobin ( GHbA1) , fasting serum insulin (FSI) and fasting C-peptide (FCP) of patients in the 4 groups were compared. All data were analyzed using analysis of variance, LSD-t test, paired t test or chi-square test. Results The clinical effects of the 4 different operative procedures on the gastric diseases were similar. The levels of FBG were (8.0 ±2.9)mmol/L before operation and (5.9 ±0.7)mmol/L after operation in the RY group, with a significant difference (t = 2. 342, P < 0. 05). The preoperative level of GHbA1 in the RY group was 7.7% ± 1.1%, which was significantly higher than 6. 9% ± 0. 6% at 2 months after the operation and 6. 1 % ± 0. 4% at 6 months after the operation (t = 4. 920, 3.012, P < 0.05). The preoperative level of FCP in the RY group was (1.30 ±0.54) μg/L, which was significantly lower than (1.95 ± 0.86) μg/L at 2 months after the operation and (2.18 ± 0.63)μg/L at 6 months after the operation (t =6. 063, 4. 651, P < 0.05). The levels of FSI in the RY group at postoperative month 1, 2 and 6 were (18 ±5) , (19 ±3) , (21 ±3) mU/L, which were significantly higher than the level of FSI [(11 ±4) mU/L]before operation (t =3. 158, 4. 502, 7. 517, P <0. 05). Preoperative levels of FBG, GHbA1, FSI and FCP in the B Ⅱ group were (8. 3 ± 1. 3) mmol/L, 7. 7% ±0. 9% , (13±4)mU/L and (1.34±0.48) μg/L, which were ignificantly different from (6.7 ± 1.2)mmol/L, 6.8%± 0.8%, (18±4)mU/L and ( 1.68 ±0.46) μg/L at postoperative month 1, (6.4 ± 1.3)mmol/L, 6.3% ±0.6% ,(18±4)mU/L and (1. 96 ± 0. 67) μg/L at postoperative month 2, and (5. 6 ±0. 7) mmol/L, 6.0%±0.3%, (19 ± 4) mU/L and (2.27 ± 0. 59) |μg/L at postoperative month 6 (t = 2. 468, 2. 598, 6. 028; 3. 055, 4. 586,4.572; 3.618, 5.860, 8.577; 2.300, 3.511, 3.943, P<0.05). The levels of FBG,GHbA1 and FCP in the 4 groups at 2 months after surgery were significantly different from those at 6 months after surgery (F = 4. 699,14. 378; 7.411, 29. 192; 3. 335, 9. 334, P < 0.05). The levels of FSI in the 4 groups at different time points were significantly different (F =2. 896, 7. 012, 11. 998, P < 0.05). Conclusion The efficacy of gastric bypass surgery for the treatment of nonobese type 2 diabetes mellitus is satisfactory.

Objective To investigate the mechanism of gastric bypass surgery in the treatment of type 2 diabetes mellitus in a rat model. Methods Seventy-two 8-week-old GK rats were randomly divided into operation group, sham operation group, diet control group and control group (18 rats in each group) according to the random number table. Rats in the operation group and the sham operation group received gastric bypass surgery and transection and reanastomosis of the gastrointestinal tract, respectively. The food intake was set as 15 g/d for each rat in the diet control group, while rats in the control group were fed ad libitum. The levels of fasting blood glucose ( FBG), postprandial blood glucose (PPBG) and glucagon-like peptide-1 (GLP-1) were detected before operation and at postoperative week 2, 4 and 8. The levels of PPBG and GLP-1 were detected at postoperative week 2, 4 and 8, then 6 rats of each group were sacrificed to detect the apoptosis of islet B cells using the TUNEL method. All data were analyzed using the t test. Results In the operation group, the preoperative levels of FBG and PPBG were (16.2±0.8)mmol/L and (31.1 ± 1. L)mmol/L, respectively, which were significantly higher than (9.2± 0.6) mmol/L and (13.1 ±0.7) mmol/L at 4 weeks after the operation, and (9. 7 ± 0. 7) mmol/L and (12. 3 ± 0.7) mmol/L at 8 weeks after the operation (t = 20. 7, 49. 7; 18. 8, 39. 0, P < 0.05 ). The levels of FBG and PPBG before the operation and at 4 and 8 weeks after the operation in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = 27.7, -57.8; 11.3, -59.9; -27.4, -48.2; -13.2, -52.7; -7.0, -24.9; -18.2, -56.4, P<0.05). In the operation group, the levels of fasting GLP-1 and postprandial GLP-1 were ( 10. 7 ± 1. 0) pmol/L and (42.5 ±1.2)pmol/L, respectively, which were significantly lower than (26. 1 ±0.9)pmol/L and (90.7 ± 1.7)pmol/L at4 weeks after the operation, and (25.3 ± 1.2)pmol/L and (90.4 ±2.0)pmol/L at 8 weeks after the operation (t=42.1, -92.4; -29.1, -72.7, P <0.05). The levels of fasting GLP-1 and postprandial GLP-1 before the operation and at 4 and 8 weeks after the peration in the operation group were significantly higher than those in the sham operation group, diet control group and control group at corresponding time points (t = 48.0, 61.9; 38.0, 62.2; 50.9, 65.2; 37.0, 48. 1; 27.5, 51.6; 17.5, 52.9, P<0.05). The number of the apoptotic islet β cells in the operation group was decreased with time. The apoptosis rates in the operation group, sham operation group, diet control group and control group were 5.9%±0.7% , 47.2%± 1.0% , 21. 1%± 1. 2% , 46.5%±1.4% at 4 weeks after the operation, and 6.3%±1. 1% , 47.2%±1.0% , 21.2%±1.2% and 46.0% ± 1.4% at 8 weeks after the operation. The apoptosis rates in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = -82. 2, - 67. 0; - 27. 1, - 22. 4; - 55. 2, - 54. 6, P < 0.05). Conclusion After gastric bypass surgery, the level of blood glucose reduces and the level of GLP-1 increases which significantly inhibit the apoptosis of islet B cells in rats with type 2 diabetes mellitus.

Objective To investigate the impact of laparoscopic gastrointestinal surgery on serum protein expression in patients with type 2 diabetes mellitus(T2DM).Methods Twelve patients with T2DM received gastrointestinal surgery at Changhai Hospital of the Second Medical University from June 2008 to September 2010.Their serum samples were collected at different time points(before surgery,1 week and 1 month after surgery).Total proteins were seperated by two-dimensional(2D)gel electrophoresis.The differentially expressed proteins were analyzed by mass spectrometry and bioinformatics.Results Protein extracts of the serum samples were separated on 2D gels successfully.Twenty differentially expressed proteins in the serum after surgery were screened out.Eight proteins were successfully identified,in which the expression of 5 proteins(Rho GDP-dissociation inhibitor 1,Prohibitin,Alpha-1-anfitrypsin precursor,Serotransferrin precursor and Fibrinogen gamma chain precursor)was increased after operation,and the expression of 3 proteins(MAP3K12-binding inhibitory protein 1,Coronin-1A and Isovalery1-COA dehydrogenase) was decreased.Conclusions The expression of 20 proteins have been changed significantly in serum samples after laparoscopic gastrointestinal surgery in patients with T2DM,and 8 proteins were successfully identified.

[Objective] To examine the sensitivity of P. falciparum to the components of dihydroartemisinin (DHA) and piperaquine (PQ) in Dihydroartemisinin Compounds. [Methods] WHO (World Health Organization) standard micro test and in-vitro test were used. [Results] Survey in the year of 2001 for 61 cases and in 2004 for 28 cases showed that the DHA-resistant rate of P. falciparum in all cases was zero with inhibitory concentration of 50% (IC50) being 6.84 nmol/L and 5.67 nmol/L, and the mean concentration for complete inhibition of schizont formation was 35 nmol/L and 39 nmol/L, respectively. Survey in the year of 2001 for 75 cases and in 2004 for 29 cases showed that PQ-resistant rate of P. falciparum was 22.67% and 17.24% with IC50 being 274 nmol/L and 317 nmol/L, and the mean concentration for complete inhibition of schizont formation was 1 220 nmol/L and 1 269 nmol/L, respectively. [Conclusion] No DHA -resistance exists and PQ-resistance decreases for the treatment of P. falciparum in Dongfang city of Hainan province.

Objective To study the clinical characteristics of hereditary nonpolyposis colorectal cancer (HNPCC). WT5”HZMethods Ten kindreds of HNPCC in South Zhejiang area were analyzed. ResultsWT5”BZ Among the 10 families, 27 persons had colorectal cancer with age ranging from 19 to 71(average 45 3 years),74 percent of cases being diagnosed before the age of 50. The total of the colorectal cancer foci in 27 cases were 37, 40 percent of focis located proximal to splenic flexure, 30 percent of cases had multiple primary colorectal cancer, among which 14 8 percent of cases had synchronous multiple primary colorectal cancer, 18 5 percent of cases had metachronous multiple primary colorectal cancer. Thirteen cases died during follow-up of 1～23 years, 14 cases were still alive during follow-up of 1～28 years. KG2Conclusion HNPCC has definite charactistics that are of much help to early diagnosis.