ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

【Objective】 To discuss the effect of adding tranexamic acid(TXA) during surgery on blood loss and security during short segment lumbar spinal stenosis surgery. 【Methods】 One hundred and eight patients with lumbar spinal stenosis who were to undergo lumbar posterior fusion surgery were randomly divided into control group, TXA group and adding TXA group, with 36 patients in each group. In the control group, TXA was not used during surgery.The TXA group received intravenous infusion of 100 mL normal saline mixture containing 1 g of TXA 15 minutes before surgery after anesthesia. In adding TXA group, after the same operation in TXA group, 10 mg/kg(body weight) of TXA was infused 3 hours later. Total perioperative blood loss, dominant blood loss, hidden blood loss, intraoperative blood loss, postoperative drainage volume, and transfusion rate were recorded in the two groups. Hemoglobin (Hb), hematocrit(HCT), prothrombin time international standardized ratio (PT-INR), prothrombin time(PT), activated partial thromboplastin time(APTT), blood platelet count (BPC), D-dimer (D-D), fibringen(FIB), C-reactive protein (CRP), alanine aminotransferase (ALT), blood urea nitrogen (BUN) were measured 3 days before and after the surgery in the three groups. Postoperative adverse events were followed up. 【Results】 The total blood loss(mL) [(968.7±209.6) vs (1 369.8±276.3), (968.7±209.6) vs (1 273.9±250.2)], dominant blood loss(mL) [(590.5±164.3) vs (876.4±235.9), (590.5±164.3) vs (789.3±221.7)], intraoperative blood loss(mL) [(318.7±120.7) vs (457.8±146.6), (318.7±120.7) vs (423.9±162.3)] and postoperative drainage volume(mL) [1 day after surgery: (164.6±25.0) vs (262.3±51.7), (164.6±25.0) vs (219.8±37.1); 3 days after surgery: (107.2±18.6) vs (156.3±37.6), (107.2±18.6) vs (145.3±22.3)] of the adding TXA group were lower than those of the control group and TXA group (P<0.05), and the transfusion rate was lower than that of the control group (P<0.05).The postoperative drainage volume and transfusion rate of TXA group were lower than that of the control group (P<0.05).There was no statistical difference in the amount of hidden blood loss between the three groups (P>0.05). Compared with the preoperative results, Hb, Hct and BPC in the three groups decreased (P<0.05), and D-D, FIB and CRP increased (P<0.05), but the change degree of Hb, Hct, BPC, D-D and CRP in the TXA group and the adding TXA group was less than that in the control group (P<0.05), and the change degree of Hb, Hct, BPC, D-D and CRP in the adding TXA group was less than that in the TXA group (P<0.05).There was no statistically significant difference in PT-INR, PT, APTT, ALT and BUN between and within the three groups before and after surgery (P>0.05), and all of them were within the normal range. No serious adverse events such as deep vein thrombosis, pulmonary embolism, epilepsy, liver and kidney damage were found in all patients after postoperative follow-up. 【Conclusion】 Intraoperative addition of TXA can effectively reduce the amount of blood lost during short segment lumbar spinal stenosis surgery without increasing the risk of complications such as coagulation disorders, thrombosis, liver and kidney function damage.

Objective:To explore the application value of ventricular intracranial pressure monitoring (V-ICPM) in the treatment of unilateral temporal lobe cerebral contusion.Methods:A retrospective cohort study was conducted to analyze the clinical data of 295 patients with unilateral temporal lobe cerebral contusion admitted to 904th Hospital of PLA Joint Support Force from January 2014 to August 2021, including 172 males and 123 females; aged 14-78 years [(46.3±14.7)years]. V-ICPM was used in 136 patients (V-ICPM group), who received surgical or non-surgical treatment according to the monitoring, while not in 159 patients (non-V-ICPM group), who received routine surgery or non-surgical treatment. The two groups were compared in terms of the rates of intracranial hematoma clearance by craniotomy, decompressive craniectomy (DC) and dehydration and osmotic therapy during hospitalization, use time of 20% mass fraction of mannitol and 30 g/L hypertonic salt, displacement rate of brain midline structure of head CT≥10 mm after discharge, rate of intracranial infection, hydrocephalus and epilepsy, and Glasgow Outcome Scale (GOS) at 6 months after discharge.Results:All patients were followed up for 6-12 months [(8.9±2.1)months]. During hospitalization, the rate of intracranial hematoma clearance by craniotomy and the rate of DC in V-ICPM group were 35.3% (48/136) and 8.1% (11/136), lower than 47.2% (75/159) and 22.0% (35/159) in non-V-ICPM group ( P<0.05 or 0.01). There was no significant difference between the two groups in the rate of dehydration and osmotic therapy or the use time of mannitol (all P>0.05). The use time of hypertonic salt in V-ICPM group was (7.2±2.5)days, more than (4.1±1.8)days in non-V-ICPM group ( P<0.05). After discharge, the displacement rate of brain midline structure of head CT in V-ICPM group was 29.4% (40/136), lower than 42.8% (68/159) in non-V-ICPM group ( P<0.05). There was no significant difference between the two groups in the rate of intracranial infection, hydrocephalus and epilepsy (all P>0.05). Six months after discharge, the good rate of GOS in V-ICPM group was 91.2% (124/136), significantly better than 81.8% (130/159) in non-V-ICPM group ( P<0.05). Conclusion:For unilateral temporal lobe cerebral contusion, V-ICPM is associated with reduced rate of craniotomy exploration and DC, decreased incidence of complications and improved prognosis of the patients in spite of longer use time of hypertonic salt.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Objective:To investigate the feasibility of coronary CT angiography(CCTA)-feature tracking(FT) for assessing global and regional myocardial strain in patients with heart failure(HF).Methods:From July 2019 to December 2020, twenty-five patients diagnosed with HF from Peking Union Medical College Hospital were prospectively enrolled into the study. All patients underwent retrospective electrocardiogram-gated CCTA and cardiac MR (CMR) imaging within 7 days. CCTA-FT and CMR-FT were undertaken using cvi 42 dedicated commercial software to measure global and regional strain parameters, including global peak radial strain (GPRS), global peak circumferential strain (GPCS) and global peak longitudinal strain (GPLS), as well as peak radial strain (PRS), peak circumferential strain (PCS) and peak longitudinal strain (PLS) of left ventricular basal segment, middle segment and apical segment. Conventional left ventricular functional parameters were also calculated, including left ventricular ejection fraction (LVEF), left ventricular stroke volume (LVSV) and left ventricular mass index (LVMI). Paired t test or Wilcoxon signed-rank test was used to compare the differences of measurements between CCTA group and CMR group. Pearson or Spearman correlation analysis was used to analyze the correlation between the two groups. Inter-and intra-observer consistence in CCTA group was evaluated by intraclass correlation coefficient (ICC) analysis. Results:The effective radiation dose of CCTA examination was 6.00 (4.86,7.63) mSv. Inter-and intra-observer consistence in CCTA group was excellent, and the ICC value was 0.85-0.98. In the overall strain parameters, GPCS in CCTA group[-8.10%(-10.32%, -5.20%)] was significantly lower than that of CMR group[-8.49%(-13.79%, -5.95%)] ( Z=-2.15, P=0.031). There was no significant difference in GPRS and GPRS between the two measurement methods ( P>0.05). Strong correlations were observed between GPRS, GPCS and GPLS ( r=0.65, 0.63, 0.71,all P<0.001). For local strain parameters, PCS in the middle segment and apical segment of CCTA group were lower than those of CMR group ( Z=-2.17, -2.62, all P<0.05). There were no significant differences in PCS of basal segment, PRS and PLS of all segments between groups (all P>0.05). The PCS and PLS of basal segment, PRS of middle segment and PRS of apical segment were moderately correlated ( r=0.46, 0.52, 0.58, 0.53, P<0.05); The other local strain parameters were strongly correlated, the range of r value was from 0.64 to 0.70 (all P<0.001). For left ventricular functional parameters, LVEF, LVSV and LVMI showed no significant differences between groups ( P>0.05), and the correlation was extremely strong ( r=0.90, 0.89, 0.96, all P<0.001). Conclusions:The repeatability of CCTA-FT technique in measuring myocardial strain was good, and the correlation of parameters measured by CCTA-FT technique and CMR-FT technique was excellent. Therefore, CCTA-FT technique can be used as a new noninvasive and simple method to evaluate myocardial motor function.

Objective:To explore the efficacy and safety of neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients.Methods:Six patients with NSCLC who were diagnosed as ⅢA and received two cycles of neoadjuvant chemoimmunotherapy and surgery between September 2019 and January 2020 were described in this study.Results:Five of them experienced AEs during neoadjuvant therapy. All of them received surgery and achieved an MPR of 50%. No viable tumor cells were found in the tissues of one patient. One patient with a small bronchopleural fistula after lobectomy.Conclusion:Neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients is safe and efficient. Long-term outcomes of neoadjuvant chemoimmunotherapy combined with surgery should be further validated.

Objective    To compare the clinical effects of segmentectomy and lobectomy for ≤2 cm lung adenocarcinoma with micropapillary and solid subtype negative by intraoperative frozen sections. Methods    The patients with adenocarcinoma who received segmentectomy or lobectomy in multicenter from June 2020 to March 2021 were included. They were divided into two groups according to a random number table, including a segmentectomy group (n=119, 44 males and 75 females with an average age of 56.6±8.9 years) and a lobectomy group (n=115, 43 males and 72 females with an average of 56.2±9.5 years). The clinical data of the patients were analyzed. Results    There was no significant difference in the baseline data between the two groups (P>0.05). No perioperative death was found. There was no statistical difference in the operation time (111.2±30.0 min vs. 107.3±34.3 min), blood loss (54.2±83.5 mL vs. 40.0±16.4 mL), drainage duration (2.8±0.6 d vs. 2.6±0.6 d), hospital stay time (3.9±2.3 d vs. 3.7±1.1 d) or pathology staging (P>0.05) between the two groups. The postoperative pulmonary function analysis revealed that the mean decreased values of forced vital capacity and forced expiratory volume in one second percent predicted in the segmentectomy group were significantly better than those in the lobectomy group (0.2±0.3 L vs. 0.4±0.3 L, P=0.005; 0.3%±8.1% vs. 2.9%±7.4%, P=0.041). Conclusion    Segmentectomy is effective in protecting lungs function, which is expected to improve life quality of patients.

Objective:To observe the efficacy of free transplantation of latissimus dorsi musculocutaneous flap and anterolateral femoral skin flap in repairing the wound after the resection of the scalp squamous cell carcinoma, and to explore the indications of these two skin flaps.Methods:The clinical data of patients with scalp squamous cell carcinoma admitted to the Plastic Surgery Department of the Second Affiliated Hospital of Kunming Medical University from June 2013 to May 2019 were analyzed retrospectively. All patients showed no cancer metastasis examined with CT. None of the patients had systemic diseases such as hypertension, diabetes, vascular disease. The wounds were repaired with free transplantation of latissimus dorsi myocutaneous flaps and anterolateral thigh flaps after extensive tumor resection. The intraoperative vascular variation, the diameter of the anastomosed blood vessel, the length of the vascular pedicle, the flap size, the time of harvesting the flap, the time for anastomosis, the operation time, and the incidences of complications at the donor site and recipient site were measured or recorded in both groups.Results:A total of 21 cases were included, including 14 males and 7 females, aged from 12 to 61 years. Eleven cases were repaired with the latissimus dorsi musculocutaneous flap, and 10 cases with the anterolateral thigh flap. All the 21 flaps survived during the 1 to 2 years follow-up. No vascular variation was found in the latissimus dorsi myocutaneous flap group, whereas 2 cases of vascular variation were found in the anterolateral thigh flap. In the latissimus dorsi myocutaneous flap group, the anastomotic vessel diameter was (2.14±0.09) mm for the artery and (2.49±0.10) mm for the vein. The vascular pedicle length was (6.14±0.28) cm, and the size of the flap was (135.0±20.8) cm 2, the harvesting time was (114.8±3.0) min, the vascular anastomosis time was (20.8±0.8) min, and the operation time was (6.5±0.2) h. In the anterolateral thigh flap group, the anastomotic vessel diameter was (2.15±0.14) mm for the artery and (2.45±0.15) mm for the vein. The vascular pedicle length was (6.80±0.31) cm, and the size of the flap was (159.9±16.4) cm 2, the harvesting time was (119.8±3.6) min, the vascular anastomosis time was (21.5±0.9) min, and the operation time was (6.9±0.2) h. There was no significant difference between the two kinds of flaps in the above parameter. The incidence of total complications at the donor site was higher in the latissimus dorsi myocutaneous flap group (7 cases) than that in the anterolateral thigh flap group (4 cases). The incidence of overall complications at the recipient was lower in the latissimus dorsi myocutaneous flap group (1 case) than that in the anterolateral thigh flap group (2 cases). Conclusions:Both the latissimus dorsi myocutaneous flap and the anterolateral femoral skin flap can achieve good results in repairing the wound after the resection of the scalp squamous cell carcinoma. The latissimus dorsi myocutaneous flap has a constant blood supply, and the operative technique is relatively easy and with low risk, which is more suitable for novices. The anterolateral thigh flap is thin and with fewer complications at the donor site. It is easy to be accepted by patients and can be performed in the supine position, which is more suitable for elderly patients.

Objective:To observe the efficacy of free transplantation of latissimus dorsi musculocutaneous flap and anterolateral femoral skin flap in repairing the wound after the resection of the scalp squamous cell carcinoma, and to explore the indications of these two skin flaps.Methods:The clinical data of patients with scalp squamous cell carcinoma admitted to the Plastic Surgery Department of the Second Affiliated Hospital of Kunming Medical University from June 2013 to May 2019 were analyzed retrospectively. All patients showed no cancer metastasis examined with CT. None of the patients had systemic diseases such as hypertension, diabetes, vascular disease. The wounds were repaired with free transplantation of latissimus dorsi myocutaneous flaps and anterolateral thigh flaps after extensive tumor resection. The intraoperative vascular variation, the diameter of the anastomosed blood vessel, the length of the vascular pedicle, the flap size, the time of harvesting the flap, the time for anastomosis, the operation time, and the incidences of complications at the donor site and recipient site were measured or recorded in both groups.Results:A total of 21 cases were included, including 14 males and 7 females, aged from 12 to 61 years. Eleven cases were repaired with the latissimus dorsi musculocutaneous flap, and 10 cases with the anterolateral thigh flap. All the 21 flaps survived during the 1 to 2 years follow-up. No vascular variation was found in the latissimus dorsi myocutaneous flap group, whereas 2 cases of vascular variation were found in the anterolateral thigh flap. In the latissimus dorsi myocutaneous flap group, the anastomotic vessel diameter was (2.14±0.09) mm for the artery and (2.49±0.10) mm for the vein. The vascular pedicle length was (6.14±0.28) cm, and the size of the flap was (135.0±20.8) cm 2, the harvesting time was (114.8±3.0) min, the vascular anastomosis time was (20.8±0.8) min, and the operation time was (6.5±0.2) h. In the anterolateral thigh flap group, the anastomotic vessel diameter was (2.15±0.14) mm for the artery and (2.45±0.15) mm for the vein. The vascular pedicle length was (6.80±0.31) cm, and the size of the flap was (159.9±16.4) cm 2, the harvesting time was (119.8±3.6) min, the vascular anastomosis time was (21.5±0.9) min, and the operation time was (6.9±0.2) h. There was no significant difference between the two kinds of flaps in the above parameter. The incidence of total complications at the donor site was higher in the latissimus dorsi myocutaneous flap group (7 cases) than that in the anterolateral thigh flap group (4 cases). The incidence of overall complications at the recipient was lower in the latissimus dorsi myocutaneous flap group (1 case) than that in the anterolateral thigh flap group (2 cases). Conclusions:Both the latissimus dorsi myocutaneous flap and the anterolateral femoral skin flap can achieve good results in repairing the wound after the resection of the scalp squamous cell carcinoma. The latissimus dorsi myocutaneous flap has a constant blood supply, and the operative technique is relatively easy and with low risk, which is more suitable for novices. The anterolateral thigh flap is thin and with fewer complications at the donor site. It is easy to be accepted by patients and can be performed in the supine position, which is more suitable for elderly patients.