Objective To investigate the efficacy of antibiotic cement column combined with iliac bone graft in the treat-ment of open fracture with bone defect of distal femur.Methods From October 2014 to March 2021,16 patients of open frac-ture bone defect of distal femur were treated with antibiotic bone cement column and iliac bone graft,including 12 males and 4 females.The age ranged from 28 to 68 years old.There were 11 cases of traffic accident injury,5 cases of falling injury,3 cases as Gustilo type Ⅰ,5 cases as type Ⅱ and 8 cases as type Ⅲ A.AO classification was used:9 cases of C2 type and 7 cases of C3 type.The time from injury to final bone grafting ranged from 4 to 119 days.The length of bone defect ranged from 2 tol0 cm.Fractures healing time,complications and knee function Merchan score were recorded.Results All the 16 patients were fol-lowed up from 9 to 29 months.The incisions of 16 patients healed in one stage without postoperative infection,plate fracture,limb shortening and valgus and varus deformity.The healing time randed from 4 to 10 months.Knee joint function according to the Merchant scoring standard,showed that 8 cases were excellent,4 cases were good,3 cases were fair,and 1 case was poor.Conclusion The use of antibiotic bone cement column combined with iliac bone graft in the treatment of open and complex bone defects of distal femur is an effective surgical method to prevent infection,assist fracture reduction,increase fixation strength and significantly reduce the amount of bone grafting.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Objective: To examine the clinical value of routine contrast esophagram (RCE) for the diagnosis of anastomotic leakage (AL) after three-incision esophagectomy with cervical anastomosis. Methods: Clinical data of 1 022 patients with esophageal cancer who underwent McKeown three-incision esophagectomy with cervical anastomosis from January 2015 to December 2019 at Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute were analyzed retrospectively. There were 876 males and 146 females, aging(M(IQR)) 48(16) years (range: 36 to 84 years). There were 253 patients (24.8%) with neoadjuvant therapy, and 817 patients (79.9%) with minimally invasive esophagectomy. According to the diagnosis and treatment habits of the attending surgeons, 333 patients were included in the RCE group, and RCE was performed on the 7^th day postoperative, while 689 patients were included in the non-RCE group, and RCE was performed when the patients had suspicious symptoms. Taking clinical symptoms, RCE, CT, endoscopy and other methods as reference to the diagnosis of AL, the sensitivity and specificity were used to analyze and evaluate the efficacy of RCE for the diagnosis of AL. The data were compared by U test or χ² test between groups. Results: The incidence rate of AL after three-incision esophagectomy was 7.34% (75/1 022), including 30 cases in the RCE group and 45 cases in the non-RCE group (9.0%(30/333) vs. 6.5%(45/689), χ²=2.027, P=0.155). The diagnostic time of AL was 9(5) days postoperative (range: 4 to 30 days). Among them, 23 cases showed cervical leakages, 50 cases showed intro-thoracic leakages, and 2 cases both cervical and intro-thoracic leakages. The diagnostic time of patients with intro-thoracic leakages was longer than that of cervical leakages (10(4) days vs. 6(3) days, Z=-2.517, P=0.012). Among the 333 patients in the RCE group, 16 cases of RCE indicated leakages including 11 cases of true positive and 5 cases determined to be false positive, while 317 cases indicated no abnormalities including 19 cases developed leakages. The sensitivity and specificity of RCE to detect AL were 36.7%(11/30) and 98.3%(298/333), respectively. The Youden-index was 0.35, and the diagnostic accuracy was 92.8%(309/333). The positive and negative predictive value were 11/16 and 94.0%(298/317), respectively. Conclusions: Routine contrast esophagram after three-incision esophagectomy with cervical anastomosis has low sensitivity and high specificity in the diagnosis of AL. The diagnostic time of AL is the 9^th day after surgery. It is necessary to prolong the observation time clinically, and combine RCE with CT, endoscopy and other inspection methods for diagnosis.
Anastomosis, Surgical/adverse effects* ; Anastomotic Leak/etiology* ; Esophageal Neoplasms/surgery* ; Esophagectomy/methods* ; Female ; Humans ; Male ; Retrospective Studies ; Surgical Wound/surgery*

Objective: To investigate the effects of exosomes from human adipose-derived mesenchymal stem cells (ADSCs) on pulmonary vascular endothelial cells (PMVECs) injury in septic mice and its mechanism. Methods: The experimental research method was adopted. The primary ADSCs were isolated and cultured from the discarded fresh adipose tissue of 3 patients (female, 10-25 years old), who were admitted to the First Affiliated Hospital of Air Force Medical University undergoing abdominal surgery, and the cell morphology was observed by inverted phase contrast microscope on the 5^th day. The expressions of CD29, CD34, CD44, CD45, CD73, and CD90 of ADSCs in the third passage were detected by flow cytometry. The third to the fifth passage of ADSCs were collected, and their exosomes from the cell supernatant were obtained by differential ultracentrifugation, and the shape, particle size, and the protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and β-actin of exosomes were detected, respectively, by transmission electron microscopy, nano-particle tracking analysis and Western blotting. Twenty-four adult male BALB/c mice were adopted and were divided into normal control group, caecal ligation perforation (CLP) alone group, and CLP+ADSC-exosome group with each group of 8 according to random number table (the same grouping method below) and were treated accordingly. At 24 h after operation, tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) levels of mice serum were detected by enzyme-linked immunosorbent assay, and lung tissue morphology of mice was detected by hematoxylin-eosin and myeloperoxidase staining, and the expression of 8-hydroxy-deoxyguanosine (8-OHdG) of mouse lung cells was detected by immunofluorescence method. Primary PMVECs were obtained from 1-month-old C57 mice regardless gender by tissue block method. The expression of CD31 of PMVECs was detected by immunofluorescence and flow cytometry. The third passage of PMVECs was co-cultured with ADSCs derived exosomes for 12 h, and the phagocytosis of exosomes by PMVECs was detected by PKH26 kit. The third passage of PMVECs were adopted and were divided into blank control group, macrophage supernatant alone group, and macrophage supernatant+ADSC-exosome group, with 3 wells in each group, which were treated accordingly. After 24 h, the content of reactive oxygen species in cells was detected by flow cytometry, the expression of 8-OHdG in cells was detected by immunofluorescence, and Transwell assay was used to determine the permeability of cell monolayer. The number of samples in above were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference t test. Results: The primary ADSCs were isolated and cultured to day 5, growing densely in a spindle shape with a typical swirl-like. The percentages of CD29, CD44, CD73 and CD90 positive cells of ADSCs in the third passage were all >90%, and the percentages of CD34 and CD45 positive cells were <5%. Exosomes derived from ADSCs of the third to fifth passages showed a typical double-cavity disc-like structure with an average particle size of 103 nm, and the protein expressions of CD9, CD63 and TSG101 of exosomes were positive, while the protein expression of β-actin of exosomes was negative. At 24 h after operation, compared with those in normal control group, both the levels of TNF-α and IL-1β of mice serum in CLP alone group were significantly increased (with t values of 28.76 and 29.69, respectively, P<0.01); compared with those in CLP alone group, both the content of TNF-α and IL-1β of mice serum in CLP+ADSC-exosome group was significantly decreased (with t values of 9.90 and 4.76, respectively, P<0.05 or P<0.01). At 24 h after surgery, the pulmonary tissue structure of mice in normal control group was clear and complete without inflammatory cell infiltration; compared with those in normal control group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP alone group were more obvious; compared with those in CLP alone group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP+ADSC-exosome group were significantly reduced. At 24 h after operation, endothelial cells in lung tissues of mice in 3 groups showed positive expression of CD31; compared with that in normal control group, the fluorescence intensity of 8-OHdG positive cells of the lung tissues of mice in CLP alone group was significantly increased, and compared with that in CLP alone group, the fluorescence intensity of 8-OHdG positive cells in the lung tissues of mice in CLP+ADSC-exosome group was significantly decreased. The PMVECs in the 3^rd passage showed CD31 positive expression by immunofluorescence, and the result of flow cytometry showed that CD31 positive cells accounted for 99.5%. At 12 h after co-culture, ADSC-derived exosomes were successfully phagocytose by PMVECs and entered its cytoplasm. At 12 h after culture of the third passage of PMVECs, compared with that in blank control group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant alone group was significantly increased (t=15.73, P<0.01); compared with that in macrophage supernatant alone group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant+ADSC-exosome group was significantly decreased (t=4.72, P<0.01). At 12 h after culture of the third passage of PMVECs, and the 8-OHdG positive fluorescence intensity of PMVECs in macrophage supernatant alone group was significantly increased; and compared with that in blank control group, the 8-OHdG positive fluorescence intensity of PMVECs in macrophage+ADSC-exosome supernatant group was between blank control group and macrophage supernatant alone group. At 12 h after culture of the third passage PMVECs, compared with that in blank control group, the permeability of PMVECs monolayer in macrophage supernatant alone group was significantly increased (t=6.34, P<0.01); compared with that in macrophage supernatant alone group, the permeability of PMVECs monolayer cells in macrophage supernatant+ADSC-exosome group was significantly decreased (t=2.93, P<0.05). Conclusions: Exosomes derived from ADSCs can ameliorate oxidative damage in mouse lung tissue, decrease the level of reactive oxygen species, 8-OHdG expression, and permeability of PMVECs induced by macrophage supernatant.
Animals ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; Female ; Humans ; Lung Injury/metabolism* ; Male ; Mesenchymal Stem Cells/metabolism* ; Mice ; Sepsis/pathology*

Objective: To explore the clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 11 patients with cervical cicatrix contracture deformity after burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 3 males and 8 females, aged 5 to 46 years, with a course of cervical cicatrix contracture deformity of 5 months to 8 years. The degree of cervical cicatrix contracture deformity was degree Ⅰ in one patient, degree Ⅱ in nine patients, and degree Ⅲ in one patient. In the first stage, according to the sizes of neck scars, one rectangular skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 200 to 600 mL was placed in the back. The expansion time was 4 to 12 months with the total normal saline injection volume being 3.0 to 3.5 times of the rated capacity of expander. In the second stage, free expanded thoracodorsal artery perforator flaps with areas of 10 cm×7 cm to 24 cm×13 cm were cut out to repair the wounds with areas of 9 cm×6 cm to 23 cm×12 cm which was formed after cervical cicatectomy. The main trunk of thoracodorsal artery and vein were selected for end-to-end anastomosis with facial artery and vein, and the donor sites were directly closed. The survival of flaps and healing of flap donor sites were observed on the 14^th day post surgery. The appearances and cicatrix contracture deformity of the flaps, recovery of cervical function, and scar hyperplasia of donor sites were followed up. Results: On the 14^th day post surgery, the flaps of ten patients survived, while ecchymosis and epidermal necrosis occurred in the center of flap of one patient and healed 2 weeks after dressing change. On the 14^th day post surgery, the flap donor sites of 11 patients all healed well. During the follow-up of 6-12 months post surgery, the flaps of ten patients were similar to the skin around the recipient site in texture and color, while the flap of one patient was slightly swollen. All of the 11 patients had good recovery of cervical function and no obvious scar hyperplasia nor contracture in the flaps or at the donor sites. Conclusions: Application of expanded thoracodorsal artery perforator flaps can restore the appearance and function of the neck, and cause little damage to the donor site in reconstructing the cervical cicatrix contracture deformity after burns, which is worthy of clinical reference and application.
Arteries ; Burns/surgery* ; Cicatrix/surgery* ; Contracture/surgery* ; Female ; Humans ; Hyperplasia ; Male ; Perforator Flap ; Reconstructive Surgical Procedures ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Treatment Outcome

Objective To investigate the protective role of GPR35 inhibition on hypoxic myocardial cell line and mouse myocardial infarction (MI) model.Methods For investigating the changes of GPR35 expression in hypoxic environment,the murine myocardial cells (MCM) were divided into normoxia group and hypoxia group,the mRNA expression of GPR35 was determined by q-PCR and the protein level was measured by Western blotting 6h after incubation.For further studying the role of GPR35,MCM were divided into four groups:normoxia,hypoxia,hypoxia+vehicle,hypoxia+CID2745678 (GPR35 inhibitor,3μmol/L) group.Accordingly,the apoptosis of cardiomyocytes was measured by flow cytometer and TUNEL.For investigating the changes of GPR35 expression in the state of myocardial ischemia,the C57 male mice were divided into sham group (n=6) and MI group (n=8),the mRNA expression of GPR35 was determined by q-PCR and the protein level was measured by Western blotting 3 days after MI.For further studying the role of GPR35,the C57 mice were divided into four groups:sham (n=6),MI (n=8),MI+vehicle (n=8) and MI+CID2745678 (n=8) group.Ultrasound echocardiography was performed 4 weeks after MI.Mice were then sacrificed and the hearts were removed and stained with Masson to measure the myocardial fibrosis area.Results Compared with normoxia group,the levels of GPR35 mRNA and protein increased obviously in hypoxia group (P＜0.01,P＜0.05);Compared with hypoxia+vehicle group,the myocardial cells apoptosis in hypoxia+CID2745678 group decreased markedly (P＜0.05).Three days after MI,compared with the sham group,the levels of GPR35 mRNA and protein increased obviously (P＜0.01,P＜0.05) in MI group;Compared with MI+vehicle group,the left ventricular fraction shortening (LVFS) and left ventricular ejection fraction (LVEF) relieved obviously (P＜0.05) and myocardial fibrosis level declined markedly in MI+CID2745678 group (P＜0.05).Conclnsion Inhibition of GPR35 could decrease the apoptosis of cardiomyocytes cultured in hypoxia and attenuated the injury of myocardial ischemia.

Objective To investigate the effect of high glycolipid on mouse cardiac microvascular endothelial cells (MCMECs),clarify the role of Tom70 (translocase of the outer mitochondrial membrane 70,Tom70) in it,and explore the related mechanism.Methods MCMECs cultured with normal glucose medium were divided into normal glucose group (NG,5.5mmol/L),high glucose group (HG,25mmol/L) and HG combined with high fat group (HG+HF,glucose concentration 25mmol/L,500μmol/L,16h).Then,the expression of Tom70 in MCMECs was knocked down by siRNA,and the HG+HF group was further divided into vehicle group,Scramble siRNA group and Tom70-siRNA group.To further confirm the specific mechanism of Tom70 in MCMEC injury induced by high glycolipid,Tom70-siRNA group was subgrouped into N-acetylcysteine (NAC)-free group and NAG-containing group.Accordingly,the apoptosis levels were measured by flow cytometer,the generation of nitric oxide (NO) was detected by ELISA kit,the expressions of Tom70 were determined by immunofluorescence and qRT-PCR,and the levels of reactive oxygen species (ROS) by DHE staining and ELISA kit.Results The apoptosis level increased after exposure to HG,and the generation of NO decreased (P＜0.05),while merging HF could aggravate these injuries (P＜0.05).Moreover,HG inhibited the expressions of Tom70 and promoted the production of ROS in MCMECs (P＜0.05).Compared with HG alone,and combination with HF significantly inhibited the expression of Tom70,and significantly increased the production of ROS (P＜0.05).Most importantly,compared with the vehicle group and Scramble siRNA group,the intracellular ROS content and apoptosis rate increased in the Tom70-siRNA group,while generation of NO was significantly decreased (P＜0.01).In contrast,these damage effects mentioned above were partially reversed by the application of antioxidants NAC (P＜0.05).Conclusions High fat can further aggravate the damage on diabetic MCMECs and Tom70 could exert its effect against cardiac microvascular endothelial injury induced by diabetes via inhibiting oxidative stress.