Objective:To discuss the effect of KIAA1522 on the proliferation,migration,and invasion of lung cancer cells,and to clarify its signaling mechanism.Methods:Bioinformatics analysis was used to detect the expression levels of KIAA1522 mRNA and protein in 75 cases of human non-small cell lung cancer(NSCLC)tissues and adjacent normal lung tissues;immunohistochemical staining was used to detect the expression of KIAA1522 protein in NSCLC tissue and adjacent normal lung tissues;Western blotting method was used to detect the expression level of KIAA1522 protein in various lung cancer cell lines.KIAA1522-small interfering(siRNA)and over-expression plasmids were transfected into the lung cancer H1299 and A549 cells,respectively.The KIAA1522-siRNA experiment was divided into blank group,negative control group(si-NC group),KIAA1522-siRNA#1 group,and KIAA1522-siRNA#2 group.The KIAA1522 over-expression experiment was divided into control group,empty vector control group(OE-NC group,transfected with KIAA1522 over-expression empty vector plasmid),KIAA1522 overexpression group(OE-KIAA1522 group,transfected with KIAA1522 over-expression plasmid),KIAA1522 over-expression+MK2206 group[OE-KIAA1522+MK2206 group,co-transfected with KIAA1522 over-expression plasmid and protein kinase B(AKT)signaling pathway inhibitor MK2206],and MK2206 group(transfected with MK2206).Western blotting method was used to verify the transfection efficiencies of the cells in various groups;MTT assay was used to detect the proliferation activities of the lung cancer cells in various groups;cell scratch assay was used to detect the migration rates of lung cancer cells in various groups;Transwell chamber assay was used to detect the numbers of invasion lung cancer cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated AKT(p-AKT),total AKT(t-AKT),cyclin D1(Cyclin D1),vascular endothelial growth factor(VEGF),and epithelial-mesenchymal transition(EMT)-related proteins[vimentin(Vimentin),N-cadherin(N-cadherin),and E-cadherin(E-cadherin)]proteins in the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal lung tissue,the expression levels of KIAA1522 mRNA and protein in NSCLC tissue were significantly increased(P<0.05 or P<0.01).The immunohistochemistry staining results showed that compared with adjacent normal lung tissue,the positive expression rate of KIAA1522 protein in NSCLC tissue was significantly increased(P<0.05)and was associated with TNM stage(P<0.01).The Western blotting results showed that compared with normal lung epithelial cells BEAS-2B,the expression levels of KIAA1522 protein in lung cancer cell lines PC9,H1299,H460,A549,H1975,and H226 were significantly increased(P<0.05 or P<0.01).Compared with si-NC group,the expression levels of KIAA1522 protein in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the expression level of KIAA1522 protein in the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01).The MTT results showed that at 24,48,and 72 h of cell culture,compared with si-NC group,the proliferation activities of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the proliferation activity of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.05);compared with OE-KIAA1522 group,the proliferation activity of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the proliferation activity of the A549 cells in MK2206 group was significantly decreased(P<0.05).The cell scratch assay results showed that compared with si-NC group,the migration rates of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the migration rate of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the migration rate of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.05);compared with OE-KIAA1522+MK2206 group,the migration rate of the A549 cells in MK2206 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with si-NC group,the numbers of invasion H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the number of invasion A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the number of invasion A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the number of invasion A549 cells in MK2206 group was significantly decreased(P<0.01).The Western blotting results showed that compared with si-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.01);compared with OE-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522 group were significantly increased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly decreased(P<0.05);compared with OE-KIAA1522 group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522+MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05);compared with OE-KIAA1522+MK2206 group,the expression levels of Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05).Conclusion:The KIAA1522 protein upregulates the expression of Cyclin D1,EMT-related proteins,and VEGF protein in lung cancer cells,promoting the proliferation,migration,and invasion of lung cancer cells,and its mechanism is related to the activation of the AKT signaling pathway.

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective To evaluate the early efficacy and safety of the regimens containing delamanid and linezolid in the treatment of rifampicin resistant tuberculosis(RR-TB).Methods A total of 47 patients diagnosed with RR-TB at Public Health Clinical Center of Chengdu from August 2020 to December 2021 were enrolled,including 22 cases(46.8％)of multidrug-resistant tuberculosis(MDR-TB),8 cases(17.0％)of RR-TB,and 17 cases(36.2％)of pre-extensively drug-resistant tuberculosis(pre-XDR-TB).All patients were treated with a regimen based on delamanid and linezolid.The efficacy and safety were evaluated at 24 weeks of treatment.Results Among the 47 patients,46(97.9％)completed 24 weeks of treatment and 1(2.1％)was lost to follow-up.At 24 weeks,the sputum culture conversion rate was 100％in the 43 patients with positive baseline sputum culture.The median conversion time was 2(2,8)weeks.Imaging examination showed absorption in 46 patients(97.9％).Overall,40 patients(85.1％)experienced varying degrees of adverse events(AEs)within 24 weeks.Eleven patients(23.4％)experienced AEs possibly related to delamanid,mainly including QTcF interval prolongation(12.8％),gastrointestinal reactions(8.5％),dizziness(2.1％),headache(2.1％),and allergy(2.1％).Six patients permanently discontinued delamanid due to AEs including gastrointestinal reactions(6.4％),prolonged QTcF interval(2.1％),severe dizziness(2.1％),and drug allergy(2.1％).Patients with low baseline CD4+T lymphocyte counts(OR=0.991,95％CI:0.984-0.999)were more likely to experience delamanid-related AEs.Thirty patients(63.8％)experienced AEs possibly related to linezolid,including myelosuppression(55.3％),peripheral neuropathy(6.4％),optic neuritis occurred(2.1％),and allergy(2.1％).Three patients(6.4％)discontinued linezolid permanently due to severe anemia,peripheral neuropathy,and allergy.Conclusions The treatment regimens containing delamanid and linezolid for RR-TB showed a high sputum culture conversion rate and good tolerance at 24 weeks.Attention should be paid to gastrointestinal reactions and cellular immunity during treatment.

Objective To evaluate the early efficacy and safety of the regimens containing delamanid and linezolid in the treatment of rifampicin resistant tuberculosis(RR-TB).Methods A total of 47 patients diagnosed with RR-TB at Public Health Clinical Center of Chengdu from August 2020 to December 2021 were enrolled,including 22 cases(46.8％)of multidrug-resistant tuberculosis(MDR-TB),8 cases(17.0％)of RR-TB,and 17 cases(36.2％)of pre-extensively drug-resistant tuberculosis(pre-XDR-TB).All patients were treated with a regimen based on delamanid and linezolid.The efficacy and safety were evaluated at 24 weeks of treatment.Results Among the 47 patients,46(97.9％)completed 24 weeks of treatment and 1(2.1％)was lost to follow-up.At 24 weeks,the sputum culture conversion rate was 100％in the 43 patients with positive baseline sputum culture.The median conversion time was 2(2,8)weeks.Imaging examination showed absorption in 46 patients(97.9％).Overall,40 patients(85.1％)experienced varying degrees of adverse events(AEs)within 24 weeks.Eleven patients(23.4％)experienced AEs possibly related to delamanid,mainly including QTcF interval prolongation(12.8％),gastrointestinal reactions(8.5％),dizziness(2.1％),headache(2.1％),and allergy(2.1％).Six patients permanently discontinued delamanid due to AEs including gastrointestinal reactions(6.4％),prolonged QTcF interval(2.1％),severe dizziness(2.1％),and drug allergy(2.1％).Patients with low baseline CD4+T lymphocyte counts(OR=0.991,95％CI:0.984-0.999)were more likely to experience delamanid-related AEs.Thirty patients(63.8％)experienced AEs possibly related to linezolid,including myelosuppression(55.3％),peripheral neuropathy(6.4％),optic neuritis occurred(2.1％),and allergy(2.1％).Three patients(6.4％)discontinued linezolid permanently due to severe anemia,peripheral neuropathy,and allergy.Conclusions The treatment regimens containing delamanid and linezolid for RR-TB showed a high sputum culture conversion rate and good tolerance at 24 weeks.Attention should be paid to gastrointestinal reactions and cellular immunity during treatment.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To discuss the effects of monocyte chemoattractant protein-1(MCP-1)on the migration and invasion of lung cancer A549 cells,and to clarify the mechanisms.Methods:Immunohistochemistry method was used to detect the expression of MCP-1 protein in 80 cases of non-small cell lung cancer(NSCLC)and adjacent normal lung tissues.The human lung cancer A549 cells were cultured in vitro.The MCP-1-small interfering RNA(siRNA)experiment was divided into blank group,negative control group(si-NC group),MCP-1-siRNA-1 group,and MCP-1-siRNA-2 group.The MCP-1 over-expression experiment was divided into control group,empty vector control group(OE-NC,transfected with MCP-1 over-expression empty vector),over-expression MCP-1 group(OE-MCP-1 group,transfected with MCP-1 over-expression plasmid),over-expression MCP-1+extracellular regulated protein kinase(ERK)pathway inhibitor PD98059 group(OE-MCP-1+PD98059 group,co-transfected with MCP-1 over-expression plasmid and PD98059),and PD98059 group(transfected with PD98059).The MCP-1 siRNA and plasmids were transfected into the lung cancer A549 cells;Western blotting method was used to verify the transfection efficiencies of the cells in various groups;the migration rate and the number of invasion cells in various groups were observed by wound healing assay and Transwell chamber assay,respectively;Western blotting method was also used to detect the expression levels of phosphorylated ERK(p-ERK),total ERK(t-ERK),and epithelial-mesenchymal transition(EMT)-related proteins in the A549 cells in various groups.Results:Compared with adjacent tissue,the positive expression rate of MCP-1 protein in NSCLC tissue was significantly increased(P<0.05),and the expression level of MCP-1 protein was related to TNM stage and lymph node metastasis(P<0.05).Compared with si-NC group,the expression level of MCP-1 protein in the cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups was significantly decreased(P<0.01).Compared with control group and OE-NC group,the expression level of MCP-1 protein in the cells in OE-MCP-1 group was significantly increased(P<0.01).The wound healing assay results showed that compared with si-NC group,the migration rate of the cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups were significantly decreased(P<0.01).Compared with OE-NC group,the migration rate of the cells in OE-MCP-1 group was significantly increased(P<0.01);compared with OE-MCP-1 group,the migration rate of the cells in OE-MCP-1+PD98059 group was significantly decreased(P<0.01).Compared with OE-MCP-1+PD98059 group,the migration rate of the cells in PD98059 group was significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with si-NC group,the number of invasion cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups was significantly decreased(P<0.01).Compared with OE-NC group,the number of invasion cells in OE-MCP-1 group was significantly increased(P<0.01);compared with OE-MCP-1 group,the number of invasion cells in OE-MCP-1+PD98059 group was significantly decreased(P<0.01);compared with OE-MCP-1+PD98059 group,the number of invasion cells in PD98059 group was significantly decreased(P<0.01).The Western blotting results showed that compared with si-NC group,the expression levels of p-ERK,Vimentin,and N-cadherin protein in the cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups were significantly decreased(P<0.05 or P<0.01),and the expression level of E-cadherin proteins was significantly increased(P<0.01).Compared with OE-NC group,the expression levels of p-ERK,Vimentin,and N-cadherin proteins in the cells in OE-MCP-1 group were significantly increased(P<0.01),and the expression level of E-cadherin protein was significantly decreased(P<0.01).Compared with OE-MCP-1 group,the expression levels of p-ERK,Vimentin,and N-cadherins proteins in the OE-MCP-1+PD98059 group were significantly decreased(P<0.01),and the expression level of E-cadherin protein was significantly increased(P<0.05).Compared with OE-MCP-1+PD98059 group,the expression levels of p-ERK,Vimentin,and N-cadherin proteins in the cells in PD98059 group were significantly decreased(P<0.05 or P<0.01),and the expression level of E-cadherin protein was increased(P<0.01).Conclusion:MCP-1 protein can upregulate the expression of EMT-related proteins in the lung cancer A549 cells,and promote the migration and invasion of the lung cancer A549 cells;its mechanism may be related to the activation of the ERK signaling pathway.

Objective To explore the influence of gender on the prognosis of patients with atrial fibrillation(AF)undergoing left atrial appendage occlusion(LAAO).Methods All non-valvular AF patients who were admitted in our hospital and underwent LAAO from August 2014 to August 2021 were enrolled and grouped according to gender.Their general information,including gender,age,comorbid underlying diseases,and results of transthoracic echocardiography and transesophageal echocardiography(TEE)were collected.The incidences of device-related thrombosis(DRT),pericardial tamponade,stroke,bleeding,hospitalization for heart failure,and cardiac death were recorded during follow-up.The influence of gender on the prognosis of these patients was analyzed.Results There were totally 673 patients with non-valvular AF were enrolled,including 366 males and 307 females,at a mean age of 68.2±9.4 years.When compared with the male patients,the female ones had a higher CHA2DS2-VASc score(P＜0.01),but smaller proportions of history of stroke,average compression ratio of occluders,and incidence of residual shunt(＜3 mm)after occlusion(P＜0.05).In 45～60 d after surgery,TEE revealed that there were 17 cases of DRT,including 8 males(2.2％)and 9 females(2.9％),though without statistical difference between the groups.Among the 17 DRT cases,1 experienced stroke,and the incidence of stroke was 5.9％in those with DRT and 0.5％without.There were 4 cases of postoperative pericardial tamponade,including 1 in the male group and 3 in the female group(no significant difference),and all of them were improved after pericardial puncture and fluid extraction.During the follow-up period of 40.2±20.5 months,no obvious differences were observed between the 2 groups in terms of stroke,bleeding,hospitalization for heart failure,and cardiogenic death.Conclusion Gender shows no significant effect on the prognosis of patients with non-valvular AF after LAAO.