Cerebral fat embolism following autologous fat injection in facial reconstruction:A case report

BACKGROUND Autologous fat injection in facial reconstruction is a common cosmetic surgery.Although cerebral fat embolism(CFE)as a complication is rare,it carries serious health risks.CASE SUMMARY We present a case of a 29-year-old female patient who developed acute CFE following facial fat filling surgery.After the surgery,the patient experienced symptoms including headache,nausea,vomiting,and difficulty breathing,which was followed by neurological symptoms such as slurred speech and left-sided weakness.Comprehensive physical examination and auxiliary investigations,including blood tests,head and neck computed tomography angiography,and cranial magnetic resonance diffusion-weighted imaging,were performed upon admission.The clinical diagnosis was acute cerebral embolism following facial fat filling surgery.Treatment included measures to improve cerebral circulation,dehydration for intracranial pressure reduction,nutritional support,and rehabilitation therapy for left limb function.The patient showed a significant improvement in symptoms after 2 weeks of treatment.She recovered left limb muscle strength to grade 5,had clear speech,and experienced complete relief of headache.CONCLUSION Our case highlights the potential occurrence of severe complications in patients undergoing fat injection in facial reconstruction.To prevent these complications,plastic surgeons should enhance their professional knowledge and skills.

Postoperative complications of concomitant fat embolism syndrome, pulmonary embolism and tympanic membrane perforation after tibiofibular fracture: A case report

BACKGROUND Fat embolism syndrome(FES)is a rare disease characterized by pulmonary distress,neurologic symptoms,and petechial rash and seriously threatens human life and health.It is still neglected clinically because of the lack of verifiable diagnostic criteria and atypical clinical symptoms.No studies on FES with pulmonary embolism(PE)and tympanic membrane perforation have been reported to date.Here,we report a rare case of concomitant FES,PE and tympanic membrane perforation after surgery in a patient with a tibiofibular fracture.CASE SUMMARY A 39-year-old man presented with right lower extremity pain due to a car accident while driving a motorbike on the road.X-ray and computed tomography scans revealed a fracture of the right mid-shaft tibia and proximal fibula categorized as a type A2 fracture according to the AO classification.A successful minimally invasive operation was performed 3 d after the injury.Postoperatively,the patient developed sudden symptoms of respiratory distress and hearing loss.Early diagnosis was made,and supportive treatments were used at the early stage of FES.Seven days after surgery,he presented a clear recovery from respiratory symptoms.The outcome of fracture healing was excellent,and his hearing of the left ear was mildly impaired at the last follow-up of 4 mo.CONCLUSION Concomitant FES,PE and tympanic membrane perforation are very rare but represent potentially fatal complications of trauma or orthopedic surgery and present with predominantly pulmonary symptoms.Early diagnosis and treatment can reduce the mortality of FES,and prevention is better than a cure.

Cerebral Fat Embolism Syndrome from Penetrating Trauma: A Rare Cause-and-Effect

A 42 year-old male sustained an accidental rifle gunshot wound to his left foot, resulting in fracture deformities of the calcaneus, navicular, cuneiform, 1st and 2nd metatarsal bases, and talus. As he was transported to our trauma center, he developed progressive encephalopathy. Urgent external fixator placement under general anesthesia was postponed due to his encephalopathy of unknown etiology. Brain magnetic resonance imaging demonstrated a “starfield” pattern of infarcts, consistent with cerebral fat embolism syndrome. Subsequently, he underwent uneventful general anesthesia. The patient was managed supportively and continued to have persistent neurologic dysfunction two months after injury.

Early acute fat embolism syndrome caused by femoral fracture: A case report

BACKGROUND Fat embolism syndrome(FES)is a rare complication caused by the presence of fat particles in the microcirculation,which usually occurs within 12-72 h after trauma.At present,there have been few cases of fat embolism presenting within 3 h after trauma.Here,we report a case of femoral fracture complicated with an acute fat embolism caused by a car accident.CASE SUMMARY A 29-year-old woman with pain,swelling and limited movement of her left lower limb after a car accident was taken by ambulance to our hospital.X-ray examination showed fracture of the middle and lower part of the left femur and fracture of the base of the left fifth metatarsal bone.She was hospitalized and admitted to the orthopedic ward.After the attending doctor performed tibial tubercle bone traction,the patient became confused,followed by respiratory distress.Finally,she was transferred to the intensive care unit.After nearly a month of treatment in the intensive care unit,the patient's cognitive function gradually recovered over 6 mo.CONCLUSION For patients with early traumatic fractures,young emergency physicians and orthopedics should be aware of the possibility of FES.

Fat Embolism Syndrome in a Patient with Bilateral Tibial Fractures: Report of the Case and Review of the Literature

Background: Although the original clinical description of fat embolism syndrome (FES) dates from 1873, the condition remains a diagnostic challenge for modern clinicians. The syndrome is described as a serious consequence of fat emboli producing a distinct pattern of clinical symptoms and signs. It is mainly associated with fractures of the long-bones and the pelvis. The present paper describes the case of a trauma patient with bilateral tibial fractures that present the syndrome and highlights the importance of early identification and aggressive treatment of FES which is obligatory for the patient’s survival. Case Description: A 32 year-old man reached the hospital as a trauma call after a road traffic accident. Clinical examination was unremarkable with the only finding that the patient was unable to straight leg raise and weight bear. Both shins were painful and swollen at their middle third, while the left one was in varus and posterior displacement. Neurovascular status of both lower extremities was normal. Plain radiographic control (X-Rays) revealed an oblique right tibial fracture of the mid-shaft with a distal third fibular fracture and a comminuted fracture of the left tibia with a fracture of the fibula at the same level. The legs were immobilised on a splint and the decision was to treat the patient surgically. Within a few post admission hours the haemoglobin dropped by 2.9 mg/dL, however a source of active bleeding could not be allocated. The abdomen was soft and not tender in palpation and the central nervous system did not present any abnormalities. The following day the haemoglobin dropped but the new ultrasonography control did not reveal any free abdominal fluid. Both lower limbs were not compromised. The second post-injury day the patient went to theatre and the right tibia was stabilised with an antegrade nail (T2-Stryker) while the left one with an external fixation. During the reaming process the haemoglobin dropped to 7.1 gr/dL, so he was transfused with 3 blood units. Immediately after extubation, the patient desaturated on air and ABG values forced the anaesthetists to intubate him in recovery and place him in mechanical ventilation with high levels of positive end expiratory pressure (PEEP). Symptoms subsided rapidly and he was transferred to the IMU. Clinical image and CT scan were in favour of fat embolism syndrome. On the fifth post-operative day the patient was transferred back to ward and a week later he was discharged being completely free of symptoms. Clinical Relevance: Fat embolism syndrome is typically presented with the following triad: a) respiratory changes;b) neurologic abnormalities;c) petechial rash. These three constitute the major criteria described by Gurd and are pathognomonic for the condition. The patient—described in the present case report—developed progressively all those symptoms within the expected period of time. The FES is a well-known pathological condition that is well described in literature and should be familiar to those clinicians that manage trauma patients. Diagnosing the condition can be highly demanding since there are no laboratory investigations or radiographic imaging techniques specific for FES. Suspicion and diagnosis can be mainly placed based on the criteria described by Gurd, in 1970.

Thrombus Propagation across an Inferior Vena Cava Filter Resulting in Fatal Pulmonary Embolism: A Case Report

Inferior vena cava (IVC) filters have since been implanted in the 1970s. The aim of implantation is to prevent the occurrence of fatal pulmonary embolism (PE). However, fatal pulmonary embolisms have been occurring after filter insertion. The mechanism is that either a thrombus or an embolus was already located cranial to the site of deployment of the filter within the inferior vena cava. And so after the filter implantation significant embolism can still occur. We present the case of a 62-year-old woman who had an IVC filter but died two weeks later from pulmonary embolism, through an unusual mechanism. The patient had a fracture of the left tibia, had open reduction and internal fixation developed pulmonary embolism secondary to deep vein thrombosis of the left lower limb. Anticoagulation was started, an IVC filter was inserted and she was discharged home with a therapeutic INR. However, she passed away two weeks later from pulmonary embolism, through the unusual mechanism of thrombus propagation across the IVC filter. The clinical significance of this article is to draw clinicians’ attention to the existence of another mechanism of fatal pulmonary embolism after an IVC filter insertion. The thrombus can propagate across the IVC filter leading to fatal pulmonary embolism.

Fatal pulmonary embolism after surgery for a clavicle fracture: A case report

Patients undergoing upper extremity surgery generally have a low risk of pulmonary embolism. We encountered a rare case of fatal pulmonary embolism after surgical treatment of a clavicle fracture. A 46-year-old man fell off the roof of his car and suffered fractures of the left clavicle, temporal bone and ribs, as well as cerebral and lung contusions. He was admitted to a local hospital, and was later transferred to our hospital for surgical treatment of the clavicle fracture at 6 days after injury. He had no dyspnea and was ambulant. On day 7 after the injury, open reduction and internal fixation of the clavicle fracture using a plate and screws were performed under general anesthesia. Although surgery was uneventful, the patient had bradycardia postoperatively that progressed to cardiopulmonary arrest, which required resuscitation and intubation. Spontaneous cardiac output was restored 10 minutes after cardiac arrest, but the GCS score was E1V1M2. Enhanced CT of the chest revealed a 15 mm defect in the right pulmonary artery, leading to a diagnosis of pulmonary embolism. Thrombolytic therapy was started immediately. However, the patient’s condition worsened and he died 20 days postoperatively. We suggest that use of mechanical and chemical thromboprophylaxis should be considered for clavicle surgery.

Fatal left atrial air embolism as a complication of percutaneous transthoracic lung biopsy:A case report

BACKGROUND Computed tomography(CT)-guided percutaneous lung biopsy is a common protocol in the context of diagnostic thoracic oncology,but entails a risk of complications including systematic air embolism(SAE).While SAE is often well tolerated,it can be difficult to treat and may result in rapid mortality in some cases.CASE SUMMARY We report a rare case of left atrial SAE in a 71-year-old woman who underwent a CT-guided lung biopsy of a pulmonary nodule in the posterior basal segment of the right lower lobe.Shortly following needle extraction,she experienced a mild cough,hemoptysis,rapid-onset unconsciousness,and cardiopulmonary arrest.Cardiopulmonary resuscitation was immediately performed,but the patient died 40 min after the procedure.A closer review of collected CT scans revealed the presence of a large volume of air within the left atrium.CONCLUSION Although SAE is generally well tolerated and asymptomatic,interventional radiologists must be aware of the risk of fatal outcomes and establish appropriate emergency management protocols.In this report,the characteristics,mechanisms,and treatment recommendations associated with SAE are discussed in an effort to improve the survival of affected patients.

Suspected cerebrovascular air embolism during endoscopic esophageal varices ligation under sedation with fatal outcome: A case report

BACKGROUND Air embolism is a very rare,yet serious and potentially fatal complication of digestive endoscopic treatment.Air embolism is the result of air directly entering the arteries or veins.However,to recognize neurological dysfunction under sedation can be difficult.Therefore,it is extremely important to identify high-risk groups and take preventive measures.CASE SUMMARY Herein,we report a 74-year-old female patient with esophageal varices who suffered from consciousness disturbance after the third endoscopic ligation of esophageal varices under sedation.Combined with the patient’s imaging examination results and medical history,we highly suspected that the patient had developed paradoxical cerebral air embolism during endoscopic ligation.We learned that the patient died at a later follow-up.In order to be able to identify and prevent the occurrence of air embolism early,we summarize and analyze the risk factors,pathogenesis,clinical manifestations,prevention and treatment options of gastrointestinal endoscopy complicated by cerebral air embolism.CONCLUSION Electroencephalographic monitoring helps to recognize the occurrence of air embolism in time and increase the patient's chance of survival.

Lysine 2-hydroxyisobutyrylation levels determined adipogenesis and fat accumulation in adipose tissue in pigs

Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear.Lysine 2-hydroxyisobutyrylation(Khib),is a novel protein post-translational modification(PTM),which play an important role in transcription,energy metabolism and metastasis of cancer cells,but its role in adipogenesis and fat accumulation has not been shown.Results In this study,we first analyzed the modification levels of acetylation(Kac),Khib,crotonylation(Kcr)and succinylation(Ksu)of fibro-adipogenic progenitors(FAPs),myogenic precursors(Myo)and mesenchymal stem cells(MSCs)with varied differentiation potential,and found that only Khib modification in FAPs was significantly higher than that in MSCs.Consistently,in parallel with its regulatory enzymes lysine acetyltransferase 5(KAT5)and histone deacetylase 2(HDAC2)protein levels,the Khib levels increased quadratically(P<0.01)during adipogenic differentiation of FAPs.KAT5 knockdown in FAPs inhibited adipogenic differentiation,while HDAC2 knockdown enhanced adipogenic differentiation.We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs(Laiwu pigs)and lean-type pigs(Duroc pigs),respectively.Accordingly,the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese-and lean-type pigs.Conclusions From the perspective of protein translational modification,we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs,and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.

Fatal air embolism during endoscopic retrograde cholangio-pancreatography (ERCP): a case report

A 61-year-old woman was diagnosed with common bile duct stones and acute biliary pancreatitis. She had previously undergone cholecystectomy 5 years ago. A planed endoscopic retrograde cholangio-pancreatography (ERCP) was arranged under general anesthesia. The patient was posed at prone position without bronchial intubation. Endoscopic access was achieved smoothly and cholangiography revealed mild dilation of the extrahepatic bile duct with mild graduate taper at ampullary region. Some filling defects were found inside lower CBD. A moderate sphincterotomy was made unremarkably, and some tiny stones were retrieved using a Dormia basket. A retrieval balloon was advanced into bile duct to make occlusion cholangiogram. At this moment, the endoscope lost its location into part one of duodenum. When the scope reaches back to descending duodenum, active bleeding was found coming out from orifice of papilla, accompanied with decreased oxygen saturation and arrhythmia. X-ray examination demonstrated gas within hepatic vein and inferior cava vein, although no free gas was observed in the renal region or subphrenic area. The endoscope was removed immediatelyand patient was changed to supine position. Vigorous cardiopulmonary resuscitation was begun immediately, unfortunately the patient did not response to all the efforts. The causes of death were thought to be systemic air embolism with cardiopulmonary failure.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Death from Fat Embolism after Lipectomy in a Patient with Madelung’s Disease

A 56-year-old man with a long history of alcoholism and a palpable raised mass about 23 cm×12 cm in size on his neck was diagnosed with Madelung’s disease(MD);the patient also had hyperuricemia.On day 1,he underwent neck lipoma tissue resection and suddenly had dyspnea 9 h after the operation,which was followed by cardiac arrest.After heart rate resuscitation,he developed a heartbeat,but he remained in a coma and died 9 days after the operation.No obvious pathological tracheal compression from a hematoma was observed while evaluating the patient’s neck on autopsy.On microscopy,the patient had an extensive pulmonary fat embolism,partial alveolar septal rupture and hemorrhage,and fat particles,and there was extensive infiltration of macrophages,which had phagocytosed fat particles,in the alveolar cavity.There was also evidence of pulmonary infection and hypoxic-ischemic encephalopathy.The cause of death was postoperative pulmonary fat embolism resulting in pneumonia and central nervous system injury.This is the first report of a patient with MD who died of a fatal pulmonary fat embolism after neck lipoma tissue resection.Medicolegal experts and clinicians should pay sufficient attention to this case.

Cronkhite-Canada syndrome complicated with pulmonary embolism:A case report

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare disease,that causes gastrointestinal polyps,ectodermal abnormalities,and gastrointestinal symptoms.CCS is prone to thromboembolism,but clinical workers have not yet established a clinical consciousness of preventing thromboembolism.The present case illustrates pulmonary embolism(PE)complicated by CCS.CASE SUMMARY A 46-year-old male patient presented with mucus,purulent,and bloody stool.Ectodermal changes included skin pigmentation,alopecia,and nail dystrophy.Colonoscopy revealed the presence of multiple polyps.After a comprehensive evaluation,the patient was diagnosed with CCS.During the disease,he was also diagnosed with pulmonary embolism,Riehl's melanosis,and intestinal flora imbalance.After symptomatic treatment with omeprazole,mesalazine,rivaroxaban,nutritional support,and regulation of intestinal flora,the patient’s symptoms were significantly relieved.CONCLUSION CCS complicated with PE was reported for the first time in China in this study.Despite the fact that CCS is extremely rare,patients with CCS should be classified as a high-risk venous thromboembolism(VTE)population,and emphasis should be placed on venous thromboembolism risk assessment and stratification,deep venous thromboembolism screening,prevention of VTE,and careful long-term follow-up.

Oils with different degree of saturation:effects on ileal digestibility of fat and corresponding additivity and bacterial community in growing pigs

Background Oils are important sources of energy in pig diets.The combination of oils with different degree of saturation contributes to improve the utilization efficiency of the mixed oils and may reduce the cost of oil supplemented.An experiment was conducted to evaluate the effects of oils with different degree of saturation on the fat digestibility and corresponding additivity and bacterial community in growing pigs.Methods Eighteen crossbred(Duroc×Landrace×Yorkshire)barrows(initial body weight:29.3±2.8 kg)were surgically fitted with a T-cannula in the distal ileum.The experimental diets included a fat-free basal diet and 5 oil-added diets.The 5 oil-added diets were formulated by adding 6%oil with different ratio of unsaturated to saturated fatty acids(U:S)to the basal diet.The 5 oils were palm oil(U:S=1.2),canola oil(U:S=12.0),and palm oil and canola oil were mixed in different proportions to prepare a combination of U:S of 2.5,3.5 and 4.5,respectively.Results The apparent and standardized ileal digestibility(AID and SID)of fat and fatty acids increased linearly(P<0.05)as the U:S of dietary oils increased except for SID of fat and C18:2.The AID and SID of fat and fatty acids differed among the dietary treatments(P<0.05)except for SID of unsaturated fatty acids(UFA)and C18:2.Fitted one-slope broken-line analyses for the SID of fat,saturated fatty acids(SFA)and UFA indicated that the breakpoint for U:S of oil was 4.14(R^(2)=0.89,P<0.01),2.91(R^(2)=0.98,P<0.01)and 3.84(R^(2)=0.85,P<0.01),respectively.The determined SID of fat,C18:1,C18:2 and UFA in the mixtures was not different from the calculated SID of fat,C18:1,C18:2 and UFA.However,the determined SID of C16:0,C18:0 and SFA in the mixtures were greater than the calculated SID values(P<0.05).The abundance of Romboutsia and Turicibacter in pigs fed diet containing palm oil was greater than that in rapeseed oil treatment group,and the two bacteria were negatively correlated with SID of C16:0,C18:0 and SFA(P<0.05).Conclusions The optimal U:S for improving the utilization efficiency of mixed oil was 4.14.The SID of fat and UFA for palm oil and canola oil were additive in growing pigs,whereas the SID of SFA in the mixture of two oils was greater than the sum of the values of pure oils.Differences in fat digestibility caused by oils differing in degree of saturation has a significant impact on bacterial community in the foregut.

Pulmonary embolism after shoulder surgery:Is it a real threat?

Pulmonary embolism(PE)is a rare but devastating complication of shoulder surgery.Apart from increased morbidity and mortality rates,it may significantly impair postoperative recovery and functional outcome.Its frequency accounts for up to 5.7%of all shoulder surgery procedures with a higher occurrence in women and patients older than 70 years.It is most commonly associated with thrombophilia,diabetes mellitus,obesity,smoking,hypertension,and a history of malignancy.PE usually occurs secondary to upper or lower-extremity deep vein thrombosis(DVT).However,in rare cases,the source of the thrombi cannot be determined.Prophylaxis for PE following shoulder surgery remains a topic of debate,and the standard of care does not routinely require prophylactic medication for DVT prophylaxis.Early ambulation and elastic stockings are important preventative measures for DVT of the lower extremity and medical agents such as aspirin,low-molecular-weight heparin,and vitamin K antagonists are indicated for high-risk patients,long-lasting operations,or concomitant severe acute respiratory syndrome coronavirus 2 infection.The most common symptoms of PE include chest pain and shortness of breath,but PE can also be asymptomatic in patients with intrinsic tolerance of hypoxia.Patients with DVT may also present with swelling and pain of the respective extremity.The treatment of PE includes inpatient or outpatient anticoagulant therapy if the patient is hemodynamically unstable or stable,respectively.Hemodynamic instability may require transfer to the intensive care unit,and cardiovascular arrest can be implicated in fatal events.An important issue for patients with PE in the postoperative period after shoulder surgery is residual stiffness due to a delay in rehabilitation and a prolonged hospital stay.Early physiotherapy and range-of-motion exercises do not adversely affect the prognosis of PE and are highly recommended to preserve shoulder mobility and function.

Assessing the impact of concurrent high-fructose and highsaturated fat diets on pediatric metabolic syndrome:A review

High-saturated fat(HF)or high-fructose(HFr)consumption in children predispose them to metabolic syndrome(MetS).In rodent models of MetS,diets containing individually HF or HFr lead to a variable degree of MetS.Nevertheless,simultaneous intake of HF plus HFr have synergistic effects,worsening MetS outcomes.In children,the effects of HF or HFr intake usually have been addressed individually.Therefore,we have reviewed the outcomes of HF or HFr diets in children,and we compare them with the effects reported in rodents.In humans,HFr intake causes increased lipogenesis,hypertriglyceridemia,obesity and insulin resistance.On the other hand,HF diets promote low grade-inflammation,obesity,insulin resistance.Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents,there is little information about the combined effects of HF plus HFr intake in children.The aim of this review is to warn about this issue,as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population.We consider that this is an alarming issue that needs to be assessed,as the simultaneous intake of HF plus HFr is common on fast food menus.

肺腺癌中FAT1的表达及其与免疫细胞浸润关系的研究

背景与目的肺癌是癌症相关死亡的主要原因。非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌最常见的病理分型,其中又以肺腺癌占比最高。非典型性钙黏蛋白1(FAT atypical cadherin 1,FAT1)是一种受体样蛋白,在肺腺癌中存在高频率突变,其编码的蛋白在细胞黏附、细胞增殖、分化等过程中发挥着重要的作用。本研究旨在研究FAT1在肺腺癌中的表达及与免疫浸润的关系。方法通过下载癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因型-组织表达(Genotype-Tissue Expression,GTEx)相关数据,获得513例肺腺癌样本、397例癌旁样本的基因表达水平及相关临床信息。分析肺腺癌组织中FAT1基因mRNA表达水平以及FAT1基因的表达与肺腺癌患者的预后关系,通过通路富集分析探索FAT1基因调控的相关信号通路。利用免疫蛋白印迹检测FAT1在肺上皮细胞和不同肺癌细胞系中的表达差异,免疫组织化学染色法被用于检测FAT1在肺癌和癌旁组织中的表达。结果14%的肺腺癌患者中存在FAT1基因突变;TCGA数据库数据显示肺腺癌组织中FAT1 mRNA表达显著高于癌旁组织。Kaplan-Meier分析显示FAT1基因表达较高的肺腺癌患者预后较差。通路富集分析表明FAT1与肿瘤发生发展通路相关,且FAT1的表达和免疫细胞浸润密切相关,免疫组化实验证明FAT1在癌组织的表达显著高于癌旁组织。结论肺腺癌组织中FAT1 mRNA呈高表达,高表达的FAT1 mRNA与肺腺癌患者的不良预后相关。FAT1有可能成为潜在的肺癌诊治靶点。

Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.