Objective To determine the effect of isopsoralen(ISO)on the healing of tibia fracture in mice and explore its underlying mechanism.Methods Fifty male C57BL/6 mice(2 month old,20±2 g)were randomly divided into model group and ISO treatment group,with 25 animals in each group.From the 3rd day after modeling,the mice from the ISO group were given an intragastric gavage of 40 mg/kg ISO,once per day for 28 consecutive days,while those of the model group was given same volume of normal saline in same way.On the 7th,14th,21st,and 28th day after gavage,the tibia on the surgical side was taken,and the fracture area was quantified by bone volume/total volume(BV/TV)after micro-CT scanning.The healing and shaping of the fracture end were observed through HE staining.ELISA was used to detect the serum contents of bone alkaline phosphatase(BALP)and procollagen type I N-terminal peptide(PINP)on the 14th day of gavage.Western blotting was employed to determine the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX,and VEGF in the tibial callus tissue in 7 and 14 d after gavage.Vascular perfusion was applied to observe the callus microvessels in 28 d to quantitatively analyze the vascular volume fraction and vessel diameter.Immunohistochemical staining was conducted to observe the expression of VEGF in the callus in 14 d after gavage.Results HE staining displayed that the ISO group had faster healing process than the model group.Micro-CT quantification results showed that the ISO group had higher BV/TV ratio in 7 d after gavage though no statistical difference,significantly higher ratio in 14 d(P＜0.05),but obviously lower ratio in 21 and 28 d after gavage(both P＜0.05)when compared with the model group.The serum contents of BALP and PINP were also remarkably higher in the ISO group than the model group(P＜0.05).Western blotting results indicated that the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX and VEGF in the ISO group were higher than those in the model group(P＜0.05).The results of angiography revealed that the vascular volume fraction and vessel diameter were notably increased in the ISO group than the model group(both P＜0.05).Immunohistochemical assay showed that the expression of VEGF was higher in the ISO group than the model group(P＜0.05).Conclusion ISO can improve the activity of osteoblasts,increase the expression of osteogenesis-related proteins,and accelerate the angiogenesis to promote fracture healing.

Gastric cancer with hemorrhage and cerebral infarction is a serious complica-tion with poor prognosis in clinic. Although the incidence rate is extremely low, the fatality and disability rates are very high. In addition, the opposition in treatment between the two complica-tions increases the difficulty of clinical diagnosis and treatment. The authors report the diagnosis and treatment of a gastric cancer patient with hemorrhage and new cerebral infarction, in order to to provide reference for related treatments.

Objective:To study the effects of a simulated plateau environment on fracture healing in rats.Methods:A rat model of mid-femoral fracture was established by hacksaw truncation and intramedullary fixation with Kirschner wires in 60 male Wistar rats which were divide into 2 groups ( n=30) by the random number table method. The rats in the control group were raised in the animal experiment center of The 940 Hospital of Joint Logistic Support Force of Chinese PLA at an altitude of 1,400 m, while the rats in the plateau group were placed in an animal experimental cabin in a simulated plateau environment at a simulated altitude of 5,000 m. The body weight was weighed once a week and X-ray films were taken every 2 weeks. Blood samples were collected after 4 weeks for detection of biochemical indicators of bone metabolism. After 8 weeks, the femurs of the surgical side were taken for bone biomechanical detection and the bone mineral density of the healthy side was detected. After 4 and 8 weeks, the femurs of the surgical side were taken for in vitro Micro-CT scanning and angiography detection. After 1, 2, 4 and 8 weeks, the femurs of the surgical side were taken for bone histopathologic detection. Results:During the entire experiment, no rats in the control group died while the mortality rate of the rats in the plateau group was as high as 26.7% (8/30). In the plateau group, some organs were pathologically damaged in the rats, fracture union was delayed, and the callus differentiated and matured slowly with the chondrocytes still dominant at the 8th week. The bone mineral density and the maximum load of the femur in the plateau group were significantly lower than those in the control group ( P< 0.05). Angiography showed that the rats in the plateau group had microvascular proliferation which did not penetrate the fracture end at the 8th week. The bone formation indexes like osteocalcin, procollagen type Ⅰ N-terminal propeptide (PⅠNP), and osteoprotegerin of the rats in the plateau group were significantly lower than those in the control group at the 4th week ( P<0.05). The bone resorption indexes like tartrate resistant acid phosphatase 5b (TRACP-5b) and receptor activator for nuclear factor-κB ligand (RANKL) in the plateau group were significantly higher than those in the control group ( P<0.05). Conclusion:A simulated plateau environment at an altitude of 5,000 m may lead to delayed fracture healing in rats.

Pulmonary hypertension is a progressive disease characterized by pulmonary vascular remodeling and eventually develops into right heart failure, which seriously affects the quality of life and safety of patients. Traditional drug therapy can alleviate disease progression, but the prognosis is poor.Mesenchymal stem cells have been shown to be effective in experimental pulmonary hypertension and right heart failure, which is an important research direction in the future.In this paper, the research progress of mesenchymal stem cells in pulmonary hypertension and right heart failure is reviewed.

Objective:To investigate the clinical effect of microdissected peroneal artery perforator flap in repair of soft tissue defect of dorsal side of the fingers.Methods:From August 2015 to July 2020, 19 patients with soft tissue defects on dorsal fingers were treated with microdissected peroneal artery perforator flap. The area of wound defect was 3.8 cm×1.5 cm-5.8 cm×3.0 cm, with exposure of phalanges and tendons. The size of flaps was 4.0 cm×1.8 cm-6.0 cm×3.3 cm. According to the size of soft tissue defects on the dorsal side of the fingers, the flaps were designed with the perforating branch of peroneal artery in the centre. The length and width of a flap were 0.2-0.3 cm bigger and wider than the area of defect. The perforator vessels with a length of 2.0-3.0 cm were arvested in the superficial layer of deep fascia. Most of the adipose tissues of the flap were removed under microscope, and the small arteries between adipose tissues were protected. The flaps were used to cover the defects of fingers. The perforator artery of the flap was anastomosed with the proper palmar digital artery of the recipient site, the accompanying vein of the perforator artery was anastomosed with the dorsal digital vein of the recipient site, and the cutaneous nerve in the flap was anastomosed with the dorsal digital nerve. The donor sites were directly pulled together and sutured intermittently. Outpatient and WeChat follow-up were conducted after operation, including wound healing, flap survival, flap sensation, donor site recovery, and flexion and extension functions of the fingers. Functional recovery was evaluated according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Results:All wounds healed in Ⅰ stage, and all 19 flaps survived. The follow-up ranged from 9 to 25 months, with an average of 11.5 months. The appearance of the flaps was satisfactory and the texture was good. Sensation recoveried to S 4 in 4 paitients, S 3 in 9 patients and S 2 in 6 patients, and with only a linear scar was left in the donor sites. The hand function recovery was evaluated according to the Trial Criteria of Upper Limb Function Evaluation of the Hand Surgery Society of the Chinese Medical Association, with 18 cases were excellent and 1 was good. Conclusion:The microdissected peroneal artery perforator flap is an ideal surgical method to repair the soft tissue defect of dorsal side of the fingers, which has good shape and simple operation, avoids the secondary thinning and plastic surgery and offers good therapeutic effects.

Objective:To explore the clinical efficacy of periosteum-covered iliac crest autografts for treatment of severe osteochondral lesions of talus （OCLTs）.Methods:A retrospective case series study was used to analyze the clinical data of 26 patients with severe OCLTs treated at Zhejiang Armed Police Corps Hospital from January 2013 to October 2019. There were 21 males and 5 females，aged 17-49 years ［（36.3 ± 10.9）years］. All patients were treated using periosteum-covered iliac crest autografts. The visual analogue scale （VAS），American Orthopedic Foot and Ankle Society （AOFAS） ankle-hindfoot score and ankle joint range of motion （ROM） were assessed before operation，6 months after operation and at the last follow-up （≥ 12 months）. The area of talus injury with MRI at the same level was recorded before operation and at the last follow-up. The healing of talus and joint surface was detected with CT at the last follow-up. The healing of the incision and osteotomy site and complications were observed.Results:All patients were followed for 12 to 22 months［（15.1 ± 3.2）months］. The VAS was （2.4 ± 0.9）points and （1.7 ± 0.6）points at postoperative 6 months and at the last follow-up，significantly lower than the preoperative （5.4 ± 1.2）points （ P < 0.01）. Meanwhile，the VAS at the last follow-up was significantly lower than that at postoperative 6 months （ P < 0.01）. The AOFAS ankle-hindfoot score was （71.7 ± 7.8）points and （87.8 ± 6.2） points at postoperative 6 months and at the last follow-up，significantly lower than the preoperative （66.5 ± 7.5） points （ P < 0.01）. Meanwhile，the AOFAS ankle-hindfoot at the last follow-up was significantly lower than that at postoperative 6 months （ P < 0.01）. The ankle ROM was （58.4 ± 5.5）° and （70.0 ± 4.9）° at postoperative 6 months and at the last follow-up，significantly improved when compared to the preoperative （42.3 ± 8.1）° （ P < 0.01）. Meanwhile，the ankle ROM at the last follow-up was significantly improved when compared to that at postoperative 6 months （ P < 0.01）. The area of talus injury with MRI at the same level was 0.67（0.55，0.89）cm 2 at the last follow-up，significantly improved when compared to preoperative 2.64（1.98，3.68）cm 2 （ P < 0.01）. The transplantation had neither obvious defects nor joint surface steps based on CT findings. All surgical incisions were healed by first intention. There were no complications such as incision infection，skin necrosis，nonunion of osteotomy，malunion or severe ankle joint disorder except that 8 patients had residual local subchondral bone?marrow?edema-like?signal?and 2 patients showed delayed healing of medial malleolus osteotomy. Conclusion:For patients with severe OCLTs，periosteum-covered iliac crest autografts can effectively relieve ankle pain，improve ankle function，and reduce the area of injury.

COVID-19/virology* ; China/epidemiology* ; Disease Outbreaks ; Genetic Linkage ; Humans ; Phylogeny ; Polymorphism, Single Nucleotide ; SARS-CoV-2/isolation & purification*

OBJECTIVE: To explore the effect of heparanase (HPSE) on apoptosis of microvascular endothelial cells (MVECs) and trans-endothelial migration of hepatocellular carcinoma (HCC) cells. METHODS: A HCC cell line with high HPSE expression was selected by real-time quantitative PCR (qRT-PCR) and Western blotting and transefected with a lentiviral vector containing an interfering RNA sequence of HPSE. Transwell migration assay was performed to detect the trans-endothelial migration (TEM) rate of the transfected HCC cells across human umbilical vein endothelial cells (HUVECs). In a Transwell indirect co-culture system, the effect of HPSE silencing in the HCC cells was determined on apoptosis of HUVECs . A nude mouse model of HCC was used to verify the effect of HPSE on apoptosis of MVECs and liver metastasis of the tumor. RESULTS: HCCLM3 cell line highly expressing HPSE was selected for the experiment. Transfection of the HCC cells with the lentiviral vector for HPSE interference the HCC cells resulted in significantly lowered TEM rate as compared with the cells transfected with the control vector ( < 0.01). In the indirect co-culture system, the survival rate of HUVECs co-cultured with HCCLM3 cells with HPSE interference was significantly higher and their apoptotic index was significantly lower than those in the control group ( < 0.05). Ultrastructural observation showed no obvious apoptosis of HUVECs co-cultured with HCCLM3 cells with HPSE interference but revealed obvious apoptotic changes in the control group. In the animal experiment, the tumor formation rate in the liver was 100% (6/6) in the control group, significantly higher than that in RNAi group (33.3%, 2/6) ( < 0.05). Under optical microscope, necrosis and apoptosis of the MVECs was detected in the liver of the control mice, while the endothelial cells remained almost intact in RNAi group. CONCLUSIONS HPSE promotes the metastasis of HCC cells by inducing apoptosis of MVECs.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Endothelial Cells ; Gene Expression Regulation, Neoplastic ; Glucuronidase ; Humans ; Liver Neoplasms ; Mice

Objective To investigate the clinicopathological features and prognosis in patients with thymoma and patients with thymoma and myasthenia gravis ( MG) . Methods A retrospective analysis was performed on the clinicopathological data of 161 patients pathologically diagnosed with thymoma alone or thymoma and MG from 2008 to 2014. In those patients, 128 had thymoma with MG and 33 had thymoma alone. The survival rates were calculated using the Kaplan?Meier method and analyzed using χ2 test or Fisher′s exact probability test. Results The mean age of onset was 45. 2 years for patients with thymoma and MG and 48. 5 years for patients with thymoma alone. In patients with thymoma and MG, 74. 2% had a tumor diameter of ≤5 cm, while 75. 8% of patients with thymoma alone had a tumor diameter of ≥5 cm. According to the Masaoka staging system, 78. 1% of patients with thymoma and MG had stage Ⅰ+Ⅱdisease, while 51. 1% of patients with thymoma alone had stage Ⅲ+Ⅳ disease. There was no significant difference in the 3?year overall survival ( OS) rate between the two groups ( 98. 1% vs. 81. 8%, P=1. 000) . The 5?year OS rate was significantly higher in patients with thymoma and MG than in patients with thymoma alone ( 91. 1% vs. 42. 9%, P= 0. 000 ) . In all patients, 140 patients with complete resection had significantly higher 3?and 5?year OS rates than 21 patients with incomplete resection ( 97. 2% vs. 58. 8%, P=0. 000;92. 7% vs. 25. 0%, P=0. 000). In patients with stage Ⅱ disease, there were no significant differences in the 3?or 5?year OS rates between patients with complete resection alone ( n=25) and patients with complete resection and postoperative radiotherapy ( n=25) ( 95% vs. 100%, P=1. 000;86% vs. 100%, P=0. 467). Conclusions Compared with patients with thymoma alone, patients with thymoma and MG have an earlier age of onset, substantially smaller tumor diameters, and earlier Masaoka stages. MG and complete resection are positive prognostic factors for patients with thymoma. Radiotherapy after complete resection can reduce the recurrence rate in patients with stage Ⅱ disease.

Objective To compare the dosimetric differences between pencil beam convolution (PBC) and anisotropic analytical algorithm (AAA) in Eclipse treatment planning system for intensitymodulated radiotherapy (IMRT) planning of lung cancer patients and dosimetric verification.Methods 10 IMRT plans of lung cancer patients were calculated using the PBC and AAA and the differences of dosimetric parameter were analyzed according to dose-volume histogram of planning target volume (PTV),lung and spinal cord.The verification measurements were performed on an inhomogeneous thorax phantom using a pinpoint ionization chamber.The agreement between calculated and measured doses was determined.The paired t test was used to compare the results.Results Compared with PBC,the AAA predicted higher maximum PTV dose (t =-4.03,P =0.010),lower minimum PTV dose (t =5.09,P =0.040),and a reduction of the volume of PTV covered by the prescribed dose.The AAA also predicted slightly increases than the PBC algorithm in the mean dose to the lung and the V20 as well as the maximum dose to the spinal cord,and the differences were statistically significant (t =-3.99,-2.79,-5.46,P =0.010,0.038,0.003).In the verification measurements,the agreement between the AAA and measurement was within 2％and superior to the PBC algorithm on isocenter (t =-3.82,P =0.012).Conclusions For IMRT treatment planning of lung cancer,the PBC algorithm overestimates the dose to the PTV and underestimates the dose to the lung and the spinal cord,so the AAA for treating planning in which the tissue inhomogeneous such as lung is present is recommended.