In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

BACKGROUND:Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity.Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.OBJECTIVE:To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.METHODS:Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method.The morphology,structure,composition,and ion release performance of the materials were characterized by scanning electron microscopy,transmission electron microscopy,energy dispersive spectroscopy,and X-ray diffraction.The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929.Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay.The extracts of the two materials were co-cultured with human umbilical vein endothelial cells.The angiogenesis-promoting properties of the materials were evaluated by Transwell assay,scratch assay,and CD31 immunofluorescence staining.The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells.The osteogenic properties of the materials were evaluated by alkaline phosphatase staining(without osteogenic induction solution)and Alizarin red staining(with osteogenic induction solution).RESULTS AND CONCLUSION:(1)The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures,and copper-doped mesoporous bioactive glass could continuously release copper ions.(2)The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility.(3)The results of Transwell assay,scratch assay,and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein,and promote angiogenesis.(4)The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass.The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.

In January 2021, a young male patient was admitted to the Department of Hand Surgery, Suzhou Ruihua Orthopeadic Hospital for a soft tissue degloving defect of distal segment of right thumb caused by machine compression. The thumb defect was reconstructed using a tiled flap with a right hallux nail flap and a lateral flap of left second toe. Donor site of the hallux nail flap was reconstructed by a lateral flap of right second toe, while the donor site of lateral flap of left second toe was covered by a skin graft of abdomen. At 1-year follow-up, the reconstructed nail was found excellent according to the established criteria. Two-point discrimination (TPD) was measured at 5 mm, and the affected thumb exhibited satisfactory flexion and extension and functions of thumb-to-palm and thumb-to-fingers oppositions. Donor sites in both feet achieved favorable appearance and function, with a Maryland foot score of 96. Only a linear scar was in abdominal donor site.

BACKGROUND:Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity.Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.OBJECTIVE:To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.METHODS:Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method.The morphology,structure,composition,and ion release performance of the materials were characterized by scanning electron microscopy,transmission electron microscopy,energy dispersive spectroscopy,and X-ray diffraction.The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929.Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay.The extracts of the two materials were co-cultured with human umbilical vein endothelial cells.The angiogenesis-promoting properties of the materials were evaluated by Transwell assay,scratch assay,and CD31 immunofluorescence staining.The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells.The osteogenic properties of the materials were evaluated by alkaline phosphatase staining(without osteogenic induction solution)and Alizarin red staining(with osteogenic induction solution).RESULTS AND CONCLUSION:(1)The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures,and copper-doped mesoporous bioactive glass could continuously release copper ions.(2)The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility.(3)The results of Transwell assay,scratch assay,and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein,and promote angiogenesis.(4)The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass.The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.

In January 2021, a young male patient was admitted to the Department of Hand Surgery, Suzhou Ruihua Orthopeadic Hospital for a soft tissue degloving defect of distal segment of right thumb caused by machine compression. The thumb defect was reconstructed using a tiled flap with a right hallux nail flap and a lateral flap of left second toe. Donor site of the hallux nail flap was reconstructed by a lateral flap of right second toe, while the donor site of lateral flap of left second toe was covered by a skin graft of abdomen. At 1-year follow-up, the reconstructed nail was found excellent according to the established criteria. Two-point discrimination (TPD) was measured at 5 mm, and the affected thumb exhibited satisfactory flexion and extension and functions of thumb-to-palm and thumb-to-fingers oppositions. Donor sites in both feet achieved favorable appearance and function, with a Maryland foot score of 96. Only a linear scar was in abdominal donor site.

Objective:To evaluate the clinical effectiveness of the reconstruction of multiple digit-tip defects with transfer of polyfoliate perforator flaps of the fibular hallux.Methods:From January 2019 to June 2022, 15 patients had undergone reconstruction surgery for multiple digit-tip defects using polyfoliate perforator flaps of ipsilateral fibular hallux, with the first dorsal metatarsal artery as the pedicle, in the Department of Upper Limb Repair and Reconstruction Surgery, Guizhou Hospital of Beijing Jishuitan Hospital. The patients were 10 males and 5 females and aged 20 to 45 years old. Eight patients had the defects of thumbs and index fingers, 4 of thumbs and middle fingers, 2 of thumb, index and middle fingers and 1 of thumb, index and ring fingers. All the 15 digit injuries had nail bed defects to which reconstructive surgery were required. For the flaps of dorsal artery, flaps were 1.8 cm×2.0 cm-2.0 cm×3.1 cm in size and for those of plantar artery, the flaps sized 1.5 cm×2.0 cm-2.5 cm×3.0 cm. Donor site defects in the hallux were reconstructed with free superficial circumflex iliac perforator flaps. Postoperative follow-up lasted until 30th June 2023 and included visits to the outpatient clinic, WeChat and telephone reviews to assess the appearance, function and sensation recovery of the digits.Results:All the 15 flaps survived. During the 6 to 24 months (16 months in average) of postoperative follow-up, the appearance and texture of all flaps were found close to the healthy digits, with good nail growth and without deformity. TPD were found between 8.0 mm and 12.0 mm. The donor sites on the great toes that reconstructed with superficial circumflex iliac artery flaps were all survived well, and the incisions were satisfactorily healed without the functions of walking, running or jumping being significantly affected.Conclusion:The use of polyfoliate perforator flaps of fibular hallux for reconstruction of multiple digit-tip defects is an ideal surgical method due to the consistency of vascular anatomy, ease with flap harvest, similarity in the normal digital skin texture, and the capability to include a nail bed with the flap. A single donor from the hallux can simultaneously reconstruct two defects of digit-tip, making it an excellent treatment in the reconstruction of small-to medium-sized composite tissue defects in multiple digits.

Objective:To explore the clinical characteristics and experiences in diagnosis and treatment of severe hand injuries caused by chaff cutters.Methods:A retrospective analysis was conducted on 60 patients (193 digits) who had mangled hand injuries caused by chaff cutters and admitted to the Department of Upper Limb Repair and Reconstruction, Beijing Jishuitan Hospital Guizhou Hospital between January 2015 and June 2022. The patients were 39 males and 21 females, with 10 to 72 (mean 42.6) years old of age. The injuries involved 41 right hands and 19 left hands. The extent of hand injuries of soft tissue and bones varied from digit-tips to wrist. Among them, 5 digits were completely destroyed in 8 cases, 3 digits including thumb were destroyed in 12 cases, 4 digits including thumb were destroyed in 10 cases, 3 or more fingers without thumb were destroyed in 8 cases, simple hand destroyed in 8 cases, digits and palm destroyed in 8 cases, and total hand destroyed in 6 cases. The sizes of wound ranged from 1.8 cm×2.0 cm to 6.8 cm×15.6 cm. Based on the wound contamination and conditions of tissue damage, surgical treatment included debridement, stump trimming, in-situ replantation, transpositional replantation, venous bridging flap transfer and emergency or phased free second toe and free flap transfers. The flap sizes were 3.0 cm×5.0 cm-7.0 cm×16.0 cm. Both the reconstructed and flap donor sites were primarily closed in one stage. Postoperative follow-ups were conducted through regular visits of outpatient clinic or via WeChat interviews. The survival and functional recovery of flap and finger were observed.Results:Of the 60 patients, emergency orthotopic replantation of 112 digits were performed with survival of 96 digits; 16 digits transposition replantation were carried out with 12 survived; 5 digits received venous bridging flap transfer with 4 survived; all 5 Flow-through anteriolateral thigh perforator flaps (ALTPFs) were survived; all of 12 phase II digit reconstructions with free second toe transfer survived; and all 18 phase II free flap transfers survived [10 ALTPFs and 8 superficial circumflex iliac artery perforator flaps(SCIAPFs)]. Postoperative complications such as wound exudation and fever happened in 8 patients, and all were rectified after debridement and symptomatic anti-infection treatment. The follow-up ranged 6 to 18 months, with 12 months in average. Hand functions were assessed using the Michigan Hand Outcomes Questionnaire (MHQ), and the scores achieved at 20.3 to 72.8 points, with 42.6 points ± 16.6 points in average.Conclusion:Severe hand injuries caused by chaff cutters are severe and complicated. A thorough assessment of wound contamination and residual digits and tissues are required. Successful surgical outcomes can be achieved through emergency and elective surgery with multiple microsurgical techniques and multi-phased surgical reconstructions, although overall functional recovery of the injured hand is often not quite realistic.

Objective:To investigate the effects of tibial second toe free flap bridged with blood flow and nerve in the treatment of severe flexion contracture of the proximal interphalangeal joint.Methods:A retrospective observational study was conducted. From March 2013 to October 2019, 9 patients with severe flexion contracture (type Ⅲ) of the proximal interphalangeal joint after trauma operation, conforming to the inclusion criteria, were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 5 males and 4 females, aged from 17 to 62 years. After the contracture tissue affecting the extension of the proximal interphalangeal joint was cut off, and the scar tissue was resected, the size of the volar wound near the proximal interphalangeal joint in extended position was 2.0 cm×1.0 cm-2.5 cm×1.5 cm, with the length of proper digital artery and nerve defect being 1.0-1.5 cm. A free flap of the same size as the wound was cut from the tibial side of the second toe and transplanted to repair the wound, and the defective proper digital artery and nerve was repaired by bridging with the tibial proper plantar digital artery and nerve of about 1.5 cm in length. The full-thickness skin graft was taken from the proximal tibial side of the lower leg to repair the wound at flap donor site. The wound at skin graft donor site was sutured directly. The survival of flap and skin graft was observed after operation. The patients were followed up, and at the last follow-up, the recovery of the affected finger and the second toe, including the donor and recipient areas were observed, the two-point discrimination distances of the flap repaired site and the pulp of the affected finger were observed and measured at the same time, the blood flow patency of bridged vessel of the affected finger was examined by Allen test, and the function of the proximal interphalangeal joint of the affected finger was evaluated according to Chinese Medical Association's standard for the range of motion of proximal interphalangeal joint.Results:The flaps and skin grafts survived smoothly after operation. The follow-up after operation lasted for 5 to 22 months, with a mean of 10 months. At the last follow-up, the flap repaired site had good shape, good color and texture, with the two-point discrimination distance being 9-12 mm, and the two-point discrimination distance of the pulp of the affected finger was 6-10 mm; the Allen test results of the affected fingers were all negative (i.e., the bridged vessels had good blood flow patency), with no recurrence of flexion contracture, and the function of the proximal interphalangeal joint was evaluated as excellent; the skin graft area of the second toe was not ruptured but was a little pigmented, and the flexion and extension activities of toe were good.Conclusions:The tibial second toe free flap bridged with blood flow and nerve has reliable therapeutic effect in the treatment of severe flexion contracture of the proximal interphalangeal joint, and the color and texture of the flap repaired area are good. Bridging to repair the severely contracted proper digital artery and nerve is beneficial to improve the blood supply of the finger body and rebuild the sensation.

Objective:To explore the imaging features of intraductal pancreatic neuro-endocrine tumor (PNET).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 17 patients with intraductal PNET who were admitted to the First Affiliated Hospital of Naval Medical University (Changhai Hospital of Shanghai) from January 2013 to October 2020 were collected. There were 7 males and 10 females, aged (47±13)years. Preoperative contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the pancreas was performed on patients. Observation indicators: (1) imaging features of intraductal PNET, including ① imaging features of CT and ② imaging features of MRI; (2) treatment and histopathological examination of intraductal PNET. Measurement data with normal distribution were described as Mean± SD and count data were described as absolute numbers. Results:(1) Imaging features of intraductal PNET. ① Imaging features of CT: 17 patients underwent preoperative contrast-enhanced CT of pancreas. There were 9 cases with tumor located in the head of the pancreas, 5 cases with tumor located in the neck of the pancreas and 3 cases with tumor located in the body and tail of the pancreas. The tumor diameter of the 17 patients was (8.7±2.5)mm, with a range of 5.2?15.5 mm. The tumor shape was round-like in the 17 patients. All the 17 patients showed isodensity on plain CT and markedly enhancement in arterial, venous and portal phases on enhanced CT. The degree of enhancement of tumor was higher than surrounding normal pancreatic parenchyma. All tumors of 17 patients were located at the truncation of main pancreatic duct (MPD) dilation, showing abrupt change in caliber of MPD without the "beak sign". The diameter of dilated MPD was (11.4±5.3)mm, with a range of 4.5?22.5 mm. Other imaging manifestations of the 17 patients included 11 cases with pancreatic parenchymal atrophy, 1 case with retention cyst, 1 case with choledochal dilation, 1 case with calcification, and all cases without cystic degeneration or hemorrhage. ② Imaging features of MRI: preoperative contrast-enhanced MRI was performed in 14 patients. Five cases showed slightly low signal but 9 cases showed unclear on T1-weighted imaging. Five cases showed low signal, 2 cases showed slightly high signal but 7 cases showed unclear on T2-weighted imaging. Of the 14 patients, 9 cases showed diffusion limited on diffusion weighted imaging and 5 cases showed unlimited diffusion. Nine cases showed marked enhancement in tumor higher than in normal pancreatic parenchyma, but 5 cases were unclear on contrast-enhanced MRI. (2) Treatment and histopathological exmination of intraductal PNET: all the 17 patients underwent surgical treatment, including 9 cases with pancreaticoduodenectomy, 4 cases with distal pancreatectomy and splenectomy, 4 cases with pancreatic segmentectomy. Postoperative histopatho-logical examination results showed 10 cases of G1 and 7 cases of G2, including 1 case of G2 with lymph node metastasis, 1 case of G2 with lymph node and liver metastasis. The pathological gross showed that the tumor body was mainly located in the pancreatic duct and blocked the pancreatic duct, with upstream pancreatic dilation. There were pancreatic acinar atrophy and fibrous tissue hyperplasia. The tumor was grayish-yellow or brownish red, solid, medium in texture and well-defined with the surrounding tissues. Microscopically, the tumor of 17 patients was mainly located in the pancreaic duct and invaded into surrounding pancreatic parenchyma. The cells of tumor were polygonal with a central nucleus, but the mitosis was rare. The cytoplasm was eosinophilic or hyaline. The tumor stroma was mainly collagen fiber with abundant capillary network.Conclusions:The imaging features of intraductal PNET are small size, marked enhancement on contrast-enhanced CT and MRI. The tumor obstructs the MPD with distal MPD dilation and pancreatic parenchyma atrophy.

Objective:To compare the numerical rating scales (NRS) and Oswestry disability index (ODI) of denosumab in Chinese postmenopausal osteoporosis patients after 3 months, and analyze the early adverse reactions to provide reference for clinical diagnosis and treatment.Methods:Using a prospective study method, 260 patients with postmenopausal osteoporosis who were outpatients and inpatients in the Second Affiliated Hospital of Soochow University from September 2020 to October 2021 were selected, and general information, including age, height, weight, bone mineral density, history of fragility fractures, and use of anti-osteoporosis drugs. All subjects received denosumab 60 mg subcutaneously, and were given calcium and vitamin D at the same time. Pain was scored by NRS before treatment and 3 months after treatment, and functional improvement was assessed by ODI.Results:After 3 months of denosumab treatment in postmenopausal women with osteoporosis, among patients with different age groups, different degrees of osteoporosis, history of fragility fractures, and history of use of anti-osteoporosis drugs, NRS score and ODI score were lower than those before treatment, and the difference was statistically significant ( P<0.05). In addition, in patients with a history of fragility fractures (mainly vertebral fractures), the NRS scores and the ODI score decreased more significantly, and the difference was statistically significant ( P<0.05); the NRS score and ODI score decreased more significantly in patients with severe osteoporosis than in patients with osteoporosis, and the difference was statistically significant ( P<0.05); the BMD value of lumbar spine was negatively correlated with the reduction of NRS score before and after treatment ( P=0.042). In this study, 260 patients had musculoskeletal pain in 6 (2.3%), fatigue in 5 (1.9%), rash in 4 (1.5%), urinary tract infection in 2 (0.7%), and dizziness in 2 (0.7%), 2 case of fever (0.7%), 1 case of hypocalcemia (0.4%), a total of 22 cases of adverse reactions were reported, and the overall adverse reaction rate was 8.5%. Conclusion:Denosumab can improve pain symptoms and functional disability early in the clinical application of Chinese postmenopausal women with osteoporosis, and the incidence of adverse reactions is low. Especially for postmenopausal female osteoporosis patients with severe osteoporosis, low lumbar spine bone density, and a history of fragility fractures (mainly vertebral fractures), the application effect is more significant.