Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.

Objective:To characterize the radial head fracture combined with capitulum cartilage injury (CCI).Methods:The data of 110 patients were analyzed retrospectively who had been treated for radial head fracture at Department of Orthopaedics, The Ninth People's Hospital of Wuxi from January 2011 to May 2020. They were 62 males and 48 females, aged from 17 to 74 years (average, 44.10 years). According to the finding of intraoperative exploration whether CCI was complicated or not, they were assigned into a CCI group and a CCI-free group. The diagnosis, location, size, type, operation method and postoperative recovery of CCI were observed in CCI group. The 2 groups were compared in terms of preoperative general data, range of forearm motion before and after operation and functional recovery of the limb by Mayo elbow performance score (MEPS).Results:CCI was complicated in 25 cases (type Ⅰ in 7 ones, type Ⅱ in 12 ones and type Ⅲ in 6 ones), involving all Mason types of radial head fracture, and located at the lateral capitellum in 13 cases, at the posterolateral capitellum in 9 cases and at the anterolateral capitellum in 3 cases. CCI was diagnosed before operation in 13 cases by physical examination after local anesthesia and imaging examination with a rate of 48% (12/25) for missed diagnosis. The preoperative flexion and extension (61.8°±13.7°) and rotation (60.0°±24.2°) in CCI group were significantly less than those in CCI-free group (77.7°±23.0° and 79.9°±21.9°) ( P<0.05); the Mason types of radial head fracture in CCI group were significantly more serious than those in CCI-free group ( P<0.05). There was no significant difference between the 2 groups in age, gender, combined injury, treatment of radial head fracture, follow-up time, range of forearm motion at the last follow-up or MEPS score ( P>0.05). Conclusions:CCI was complicated in 22.73%(25/110) of the radial head fractures in this cohort and found in all Mason types of radial head fracture, and mostly located at the lateral and posterolateral capitellum. CCI is likely to be missed by imaging examination. In patients with mild radial head fracture and suspected CCI, positive physical examination after local anesthesia is valuable for diagnosis of CCI complication and operative indication. Care should be taken to detect CCI complication by intraoperative exploration in surgery of radial head fracture.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective:To explore the advantages, disadvantages, and precautions of clinically applying four types of non-trunk vessels as recipient vessels in the free flap transplantation for repairing peri-knee wounds.Methods:A retrospective analysis of the clinical data was conducted of 23 patients (12 males and 11 females) with peri-knee skin and soft tissue defects who underwent free anterolateral thigh flaps or free latissimus dorsi flaps. The patients were admitted to the Department of Traumatic Orthopedics, Wuxi 9th People’s Hospital, from January 2015 to December 2019. The patients were aged 20-72 years (mean 41.9). The wound size with vital tissue exposure was 18.0 cm×5.0 cm-42.0 cm×9.0 cm. Preoperative color Doppler and computerized tomography angiography techniques were used to assist in positioning and to measure the recipient vessels (including the descending genicular vessel, descending branch of the lateral femoral circumflex vessel, the medial sural vessel, and the medial inferior genicular vessel) and blood vessels in the donor area (including descending branches of lateral femoral circumflex vessels and thoracic dorsal vessels). The caliber was measured and verified by a soft ruler with a scale intraoperative. The measured values of the caliber were recorded in the preoperative and intraoperative. The color and texture of the two flaps and the healing of the donor sites were observed postoperatively. The conformance ratio of preoperative and intraoperative measured values of vessels in the donor and recipient areas (except for the only case of the medial inferior genicular vessel) was compared. SPSS 26.0 software was used for data analysis. The measurement data were showed as Mean±SD, and the comparison results were analyzed by paired t-test. P<0.05 was considered statistically significant. Results:A total of 23 patients with skin and soft tissue defects around the knee were enrolled. The size of the tissue flap was 18.0 cm×5.0 cm-46.0 cm×9.0 cm. Twelve of 14 anterolateral thigh flaps anastomosed to the descending genicular vessel survived. The remaining two cases had a length of 6 cm and 4 cm necrosis at the distal flap, which was finally given skin-grafting and healed. One of the 12 survived flaps failed in limb salvage in Phase Ⅰ and was thus given flap reconstruction in Phase Ⅱ. Another case was given amputation due to serious infection of limbs, with incomplete ends of the survived flaps rotated and covered. In four cases anastomosed to the descending branch of the lateral circumflex femoral vessel, three anterolateral thigh flaps survived completely, and one distal latissimus dorsi flap had a length of 12 cm necrosis which was given debridement and Ilizarov bone transport for heal. Two anterolateral thigh flaps and two latissimus dorsi flaps anastomosed to the medial sural vessel survived completely, of which one anterolateral thigh flap had vein crisis which was later solved. The anterolateral thigh flap of 1 case anastomosed to medial inferior genicular vessels completely survived. The postoperative follow-up lasted 3-30 months with an average of 13.6 months. All the flaps have good color and textures with good incision heal at the donor site in Phase Ⅰ. There was no statistically significant difference in the preoperative and intraoperative measurement values of blood vessel caliber in the donor and recipient areas ( P>0.05). Conclusions:Four non-trunk peri-knee blood vessels can serve as recipient vessels of the free tissue flaps, and proper selection of the vessels can effectively improve the survival rate of the tissue flaps. The descending genicular vessel can serve as the recipient vessel for a priority, as with a superficial position, fixed dissection, simple positioning, and convenient intraoperative dissection.

Objective:To explore the advantages, disadvantages, and precautions of clinically applying four types of non-trunk vessels as recipient vessels in the free flap transplantation for repairing peri-knee wounds.Methods:A retrospective analysis of the clinical data was conducted of 23 patients (12 males and 11 females) with peri-knee skin and soft tissue defects who underwent free anterolateral thigh flaps or free latissimus dorsi flaps. The patients were admitted to the Department of Traumatic Orthopedics, Wuxi 9th People’s Hospital, from January 2015 to December 2019. The patients were aged 20-72 years (mean 41.9). The wound size with vital tissue exposure was 18.0 cm×5.0 cm-42.0 cm×9.0 cm. Preoperative color Doppler and computerized tomography angiography techniques were used to assist in positioning and to measure the recipient vessels (including the descending genicular vessel, descending branch of the lateral femoral circumflex vessel, the medial sural vessel, and the medial inferior genicular vessel) and blood vessels in the donor area (including descending branches of lateral femoral circumflex vessels and thoracic dorsal vessels). The caliber was measured and verified by a soft ruler with a scale intraoperative. The measured values of the caliber were recorded in the preoperative and intraoperative. The color and texture of the two flaps and the healing of the donor sites were observed postoperatively. The conformance ratio of preoperative and intraoperative measured values of vessels in the donor and recipient areas (except for the only case of the medial inferior genicular vessel) was compared. SPSS 26.0 software was used for data analysis. The measurement data were showed as Mean±SD, and the comparison results were analyzed by paired t-test. P<0.05 was considered statistically significant. Results:A total of 23 patients with skin and soft tissue defects around the knee were enrolled. The size of the tissue flap was 18.0 cm×5.0 cm-46.0 cm×9.0 cm. Twelve of 14 anterolateral thigh flaps anastomosed to the descending genicular vessel survived. The remaining two cases had a length of 6 cm and 4 cm necrosis at the distal flap, which was finally given skin-grafting and healed. One of the 12 survived flaps failed in limb salvage in Phase Ⅰ and was thus given flap reconstruction in Phase Ⅱ. Another case was given amputation due to serious infection of limbs, with incomplete ends of the survived flaps rotated and covered. In four cases anastomosed to the descending branch of the lateral circumflex femoral vessel, three anterolateral thigh flaps survived completely, and one distal latissimus dorsi flap had a length of 12 cm necrosis which was given debridement and Ilizarov bone transport for heal. Two anterolateral thigh flaps and two latissimus dorsi flaps anastomosed to the medial sural vessel survived completely, of which one anterolateral thigh flap had vein crisis which was later solved. The anterolateral thigh flap of 1 case anastomosed to medial inferior genicular vessels completely survived. The postoperative follow-up lasted 3-30 months with an average of 13.6 months. All the flaps have good color and textures with good incision heal at the donor site in Phase Ⅰ. There was no statistically significant difference in the preoperative and intraoperative measurement values of blood vessel caliber in the donor and recipient areas ( P>0.05). Conclusions:Four non-trunk peri-knee blood vessels can serve as recipient vessels of the free tissue flaps, and proper selection of the vessels can effectively improve the survival rate of the tissue flaps. The descending genicular vessel can serve as the recipient vessel for a priority, as with a superficial position, fixed dissection, simple positioning, and convenient intraoperative dissection.

Objective To synthesize a novel prostate cancer targeting gene vector PAMAM-PEG-C2min and improve gene transfection efficiency targeting on prostate cancer. Methods The aptamer (C2min) and polyamide-amine (PAMAM) were ligated by polyethylene glycol (PEG). The structure of the synthesized PAMAM-PEG-C2min was identified by NMR. The biological characteristics of the nanoparticles were examined by the uptake experiments and gene transfection experiments (the loaded gene was siR-M) with the prostate cancer cells (PC3 and LNCaP). Besides, the in vivo targeting was investigated using in vivo image system. The in vivo targeting results indicated that PAMAM-PEG-C2min can achieve the simultaneous targeting of two prostate cancer tissues. Results The PAMAM-PEG-C2min synthesis was confirmed by NMR. Cell uptake experiments showed that the cell uptake efficiency of PAMAM-PEG-C2min was concentration dependent. In vitro experiments showed that the PC3 and LNCaP cells transfection efficiency and targeting of PAMAM-PEG modified with C2min were significantly improved compared with the PEG modified PAMAM. Conclusion PAMAM-PEG-C2min is a potential targeted drug delivery vehicle. It provides a new technology platform for comprehensive and specific targeting treatment of prostate cancer.

Objective To investigate the clinical efficacy of free flap transplantation in repairing the Gustilo type ⅢB and ⅢC fractures of tibia and fibula combined with soft tissue defects.Methods A retrospective case series study was conducted on the clinical data of 46 patients who had Gustilo type ⅢB and ⅢC fractures of tibia and fibula with soft tissue defects admitted from June 2013 to January 2017.There were 34 males and 12 females,aged 1-67 years (mean,39 years).The wound defect areas ranged from 6 cm × 20 cm to 7 cm × 38 cm.According to the Gustilo fracture classification,there were 31 cases of type ⅢB and 15 cases of type ⅢC.According to the AO fracture typing,there were five cases of type A,23 type B,and 18 type C.All patients were repaired with free flap transplantation,among which 40 patients were treated with anterolateral thigh flap and six with latissimus dorsi flap.The areas of anterolateral thigh flap ranged from 6 cm × 13 cm to 14 cm ×32 cm,and those of the latissimus dorsi flap from 6 cm × 22 cm to 7 cm × 40 cm.Efficacy was evaluated by flap survival rate,complications,fracture healing time,lower limb function scoring system (LEFS),and skin flap function.Results All limbs were salvaged successfully.One case of total flap necrosis and eight cases of postoperative crisis occurred.After active exploration and treatment,three cases were seen distal local necrosis,and the total survival rate was 91％.Infection at the donor site was found in two cases.The complication incidence rate was 4％.All patients were followed up for 7-42 months,with an average of 19 months.The fracture healing time averaged 43.5 weeks,and the LEFS score averaged 54 points.According to the seven indexes of flap function,the results were excellent in 1 1 cases,good in 29 cases,fair in four cases,and poor in two cases,with an excellent and good rate of 87％.Conclusion Free flap transplantation can achieve satisfactory efficacy in treating Gustilo type ⅢB and ⅢC of tibia and fibula combined with soft tissue defects,with high limb salvage rate and good function recovery.

Objective To assess the clinical efficacy of perforators positioning technique in anterolateral thigh perforator sub lobe flap transplantation for reconstructing soft tissue defects of forearm or hand.Methods A retrospective case series study was performed to analyze 24 patients with forearm and hand soft tissue defects admitted from January 2013 to August 2017.There were 18 males and six females,aged 31-68 years (mean,52.3 years).The wound defect areas ranged from 11 cm × 10 cm to 18 cm× 14 cm.The anterolateral thigh sub lobe perforator flaps were used for repair.CT angiography (CTA) combined with color Doppler ultrasound (CDS) was used to determine the perforator position before operation.After the appropriate thigh side was selected according to the perforator position and the wound area,the lobed flaps were designed to ensure all the flaps for the stage I suture after the length was converted into width.All patients obtained stage Ⅱ repair,and the repair time was 5-29 days,with an average of 13 days.The accuracy of perforation positioning was observed during operation (the error was not more than 1 cm for accurate positioning).The flap survival and complications were recorded within 2 weeks after operation.Follow-up was performed using the seven indicators of flap function to evaluate the efficacy.Results The positioning accuracy rate was 99％.One case was seen necrosis about 2 cm at the proximal end of flap.Two cases had arterial crisis after flap operation and survived after active exploration.In two nonunion cases because of wound infection around the flap,one case was healed after dressing change,and another case was healed after debridement.The donor site of the flap obtained stage Ⅰ direct suture,and one case was seen obvious scar hyperplasia at the donor site.Flaps were made thinner in two patients with hand defects at the later stage.All 24 patients were followed up for 7-33 months,with an average of 18.3 months.According to the seven indexes of the flap function,the results were excellent in seven cases,good in 13,fair in three,and poor in onee,with an excellent and good rate of 83％.The flaps appeared soft with good color at the last follow-up.Conclusions In the treatment of soft tissue defects of forearm or hand using anterolateral thigh flap,conversion from length to width and direct suture of donor site can cover the wound well and reduce complications.Perforators positioning technique can facilitate precise preoperative planning and intraoperative accurate cutting.

Objective To study the surgical treatment of hepatic hemangiomas and the timing of surgery.Methods A retrospective study was conducted on 908 patients with giant hemangiomas who underwent surgery between December 1997 and December 2017.The clinical data,surgical indications,surgical outcomes,lesion size,and the effect of TAE were compared.Results The diameter (mean + /-S.D.)of the resected hepatic cavernous hemangiomas was (11.1 ± 6.2) cm (the longest diameter was 60 cm).585 patients (64.4％) underwent enucleation of hepatic hemangiomas and 323 patients (35.6％) underwent anatomical hepatectomy.Six patients died perioperatively (mortality rate 0.7％).The incidence of severe complication (Clavien-Dindo grade 3 ～ 5) was 3.8％.The incidence of severe postoperative complication for enucleation (2.7％) was significantly less than anatomic liver resection (5.6％,P ＜0.05).When the lesion was more than 20 cm,the complication and mortality rates were significantly higher than those less than 20 cm (P ＜ 0.05).The complication and mortality rates in patients who underwent TAE before surgery were significantly higher than those without TAE (P ＜ 0.05).Conclusions Surgical enucleation of hemangiomas was superior to anatomical hepatectomy.With increase in tumor size,the risk of surgery increased.Surgical treatment was safe and effective for giant hepatic hemangiomas.For giant hepatic hemangiomas with significant increase in size,prompt surgical treatment is recommended.