Objective To investigate the CD44v6 and heparanase in non-small cell lung cancer (NSCLC ) and adjacent normal lung tissues ,and to study the correlation of these two molecular in non-small cell lung cancer invasion and metastasis .Methods The expressing of CD44v6 and heparanase in 117 patients with non-small cell lung cancer tissues and 62 adjacent normal lung tissue was detected by immunohistochemical staining .Results The expression of CD44v6 in NSCLC was 54 .7% (64/117) ,which was sig-nificantly higher than in adjacent tissues of 4 .8% (3/62)(P<0 .05);the expression of heparanase in NSCLC was 86 .3% (101/117) ,which was significantly higher than the normal adjacent tissues 17 .7% (11/62)(P<0 .01);CD44v6 expression in NSCLC ex-pression was positive correlated with heparanase .Conclusion CD44v6 and heparanase are associated with the invasion and metasta-sis of NSCLC ,combined detection of the expression of the two molecular maybe has a certain reference value in determine the prog-nosis of NSCLC .

Objective To evaluate association of plasma levels of homocysteine, folate and vitamin B12 as well as genetic polymorphisms of homocysteine with ulcerative colitis (UC). Methods Three hundred and ten consecutive patients with UC and 936 healthy controls were recruited.Polymorphisms of methylenetetrahyrdofolate reductase (MTHFR, C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G were genotyped using PCR-RELP methods. Eighty eight patients and one hundred healthy controls were randomly selected for determination of plasma levels of homocysteine by enzymatic cycling assay, and concentrations of folate and vitamin B12 were measured by corpuscle immune chemiluminescence assay. Results The variant allele and genotype frequencies of MTHFR 1298C, MTR 2756G and MTRR 66G were significantly higher in UC patients than in the healthy controls (P＜0. 01). Moreover, plasma homocysteine level was obviously higher in UC patients than in controls [(21.73±6.59) mmol/L vs(12.47±5.01)mmol/L,P<0.01).Whereas both folate F(11.25±6.19)nmol/L] and vitamin B12 [(322.81±128.47)pmol/L] concentrations were significantly lower in UC patients than in controls [(15.28±7.72)nmol/L and (422.59±129.36)pmol/L,respectively,P<0.01].Logistic analysis revealed that abnormal levels of homocysteine,folate and vitamin B12 were independent risk factors for UC(P<0.01).Conclusions Plasma levels of homocysteine,folate and vitamin B12 as well as the related genetic polymorphisms of homocystein are correlated with UC,which provides a theoretical basis for supplement of folate and vitamin B12 in treatment of UC patients.

Objective:To investigate the efficacy of therapeutic plasma exchange with continuous renal replacement therapy in patients with early septic shock.Methods:A total of 55 patients with septic shock admitted to ICU of Mindong Hospital Affiliated to Fujian Medical University from December 2017 to December 2020 were retrospectively analyzed. The patients were divided into the therapeutic plasma exchange group ( n=29) and standard-therapy group ( n=26) according to whether plasma exchange combined with hemofiltration was used. Patients in both groups were treated according to the 2016 Surviving Sepsis Campaign guidelines. No hemofiltration or/and plasma exchange therapy was performed in the standard-therapy group. In the therapeutic plasma exchange group, hemofiltration was performed immediately after plasma exchange within 24 h. The inflammatory indexes, hemodynamic indexes, organ function scores and 28-day mortality were monitored before and 24 h after treatment. χ2 test was used for counting data, t-test was used for measurement data, and Kaplan-Meier curve was used to evaluate 28-day survival status. Results:(1) There were no differences in sex, age, underlying diseases, acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score before treatment between the two groups. (2) There were no significant differences in PCT, CRP and IL-6 between the two groups at enrollment. After treatment, PCT, CRP and IL-6 in the therapeutic plasma exchange group were significantly lower than those in the standard-therapy group [PCT (ng/mL): (50.07±14.54) vs. (57.93±13.42), P=0.043; CRP (mg/L): (85.71±46.05) vs. (115.10±44.42), P=0.042; IL-6 (pg/mL): (5 957.45±2 344.48) vs. (7 522.94±3 218.94), P=0.043], but there was no significant difference in WBC between the two groups. (3) There were no significant differences in norepinephrine dose, mean arterial pressure, heart rate, systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI) and Lactate level between the two groups. After treatment, the norepinephrine dose, lactate level and EVLWI in the therapeutic plasma exchange group decreased significantly, while SVRI increased significantly {norepinephrine dose [μg/(kg·min): (0.76±0.39) vs. (0.54±0.39), P=0.044; lactate (μmmol/ L): (7.74±4.22) vs. (4.51±1.62), P<0.001; EVLWI (mL/kg): (10.04±2.77) vs. (8.23±2.23), P=0.008; SVRI (dyn·s/cm 2): (1 103.14±364.94) vs. (1 403.31±264.46), P=0.001}. Compared with the standard-therapy, the 24-h intravenous infusion volume was significantly decreased [(3 852.07±686.43) mL vs. (4 474.81±572.71) mL, P=0.001]. (4) There were no significant differences in APACHEⅡscore and SOFA score between the two groups at enrollment. After treatment, the APACHEⅡscore and SOFA score of the therapeutic plasma exchange group were significantly lower than those of the standard-therapy group [APACHEⅡscore: (14.07±4.30) vs. (19.23±5.44), P<0.001; SOFA score: (9.93±1.16) vs. (11.69±1.81), P<0.001)]. There were no significant differences in ICU mortality and 28-day mortality between the two groups ( P>0.05). Conclusions:Therapeutic plasma exchange with continuous renal replacement therapy can reduce the inflammatory response and improve hemodynamics in patients with septic shock. However, 24 h treatment did not improve the mortality of patients.

Objective To study the correlation between the changes of matrix metalloproteinase-9(MMP-9)and neutrophil/lymphocyte ratio(NLR)before and after the revascularization of acute ischemic stroke(AIS),so as to find biomarkers to predict the bleeding transformation risk of AIS patients.Methods From February 2022 to December 2022,161 patients admitted to the Stroke Center of Qujing Hospital Affiliated to Kunming Medical University with AIS werre divided in to the hemorrhagic transformation group and the non-hemorrhagic transfor-mation groupand treated with revascularization(intravenous thrombolysis,endovascular treatment,combined the intravenous thrombolysis with endovascular treatment).Among them,there were 46 cases in the hemorrhagic transformation group and 115 cases in the non hemorrhagic transformation group.And the general data,NLR value and MMP-9 before and after the revascularization were compared between the two groups.Results There was no statistical difference in general data between the two groups(all P>0.05)except for C-reactive protein in hemorrhagic transformation group and in non-hemorrhagic transformation group(P<0.001).The white blood cells,neutrophils,neutrophil percentage,neutrophil absolute value,lymphocyte absolute value,NLR and MMP-9 value in hemorrhagic transformation group were significantly higher than those in non-hemorrhagic transformation group before the treatment and there was a statistical significance(P<0.05).After revascularization,the indexes of blood routine and MMP-9 were significantly higher than those before the revascularization,and the increase in hemorrhagic transformation group was more obvious than that in non-hemorrhagic transformation group and there was a statistical significance(P<0.001),The ROC curve showed that the area under the curve(AUC)of NLR and MMP-9 predicting bleeding transformation after AIS revascularization were 0.74 and 0.90.Conclusion NLR,MMP-9 are associated with the risk of bleeding transformation in AIS patients after the revascularization and can they can be used as the predictive factors for bleeding transformation risk.

BACKGROUND: Adenocarcinoma is the most common type of lung cancer. It has been clinically evaluated that therapiestargeting against the epidermal growth factor receptor (EGFR) as the clinical standard first-line treatment. The response and outcome of EGFR-tyrosine kinase inhibitors (TKIs) in patients harboring common mutations in EGFR kinase domain (deletion in exon19 and L858R in exon 21) has been well demonstrated, but not in rare or complex mutations. METHODS: A total of 150 patients that harbored rare or complex mutations in EGFR diagnosed by histopathology were included in this retrospective study. The clinical-pathological characteristics of all 150 patients as well as the response and progression-free survival (PFS) in 48 patients that received EGFR-TKIs in first/second/third line treatments weredescribed and analyzed. RESULTS: Patients were divided into four groups based on the mutation types: single G719X point mutation in exon 18 (n=46, 30.7%), single L861Q point mutation in exon 21 (n=45, 30.0%), other single rare mutation (n=14, 9.3%) and complex mutations (n=45, 30.0%). The result indicated thatthere was no correlation of EGFR mutation typeswith other parameters such as gender, age, clinical stage, pathology and smoking history. For the 48 patients that received EGFR-TKIs treatment, there were no significant differencesamong 4 groups in terms of objective response rate (ORR) and disease control rate (DCR) (54.5% vs 30.0% vs 0.0% vs 35.7%, χ²=3.200, P=0.34; 90.9% vs 85.0% vs 66.7% vs 92.9%, χ²=2.162, P=0.59). The median progress-free survival (mPFS) was 11.0 months (95%CI: 4.4-17.6), and in each group of different EGFR mutation types are 15.8 months (95%CI: 9.5-22.2), 8.0 months (95%CI: 5.1-11.0), 4.9 months (95%CI: 1.4-8.4) and 23.1 months (95%CI: 15.8-30.4)(χ²=7.876, P=0.049). CONCLUSIONS The efficiency of targeting EGFR-TKIs on different types of rare or complex mutations was heterogeneous. The PFS may be better in patients that harbored complex mutations than those with single rare mutations. Further studies with larger sample size are necessary. Moreover, to discover novel therapeutic targets and develop new drugs are imminentfor those patientswith no response to the existing treatments.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Disease-Free Survival ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Exons ; genetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Retrospective Studies ; Treatment Outcome

ObjectiveTo observe the effect of Tongxie Yaofang on the function of tumor-related natural killer （NK） cells under chronic stress and explore the possible molecular mechanism. MethodFifty SPF-grade BABL/C male mice were randomized into normal， model， and low-， medium-， and high-dose （6.825， 13.65， and 27.3 g·kg^-1， respectively） Tongxie Yaofang groups， with 10 mice in each group. Other groups except the blank group were subjected to 7 days of chronic restraint stress， and then forced swimming and tail suspension tests were carried out to evaluate the modeling performance. After the successful modeling， rats in Tongxie Yaofang groups were administrated with low-， medium-， and high-doses of Tongxie Yaofang by gavage， while those in the other groups were administrated with normal saline by gavage. After 14 days， each group of mice was inoculated with subcutaneous colon cancer to establish the model of colon cancer under chronic stress. The pathological changes of the tumor tissue in each group of mice were observed using hematoxylin-eosin （HE） staining. The content of CD49b-positive cells in the peripheral blood and tumor tissue of mice was measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the content of molecules associated with NK cell activation in the peripheral blood. Western blot was employed to determine the protein levels of major histocompatibility complex class Ⅰ polypeptide-related sequences A and B （MICA+MICB） and UL-16-binding protein 1 （ULBP1） in the tumor tissue. ResultCompared with the normal group， the model group showed a decrease in 5-hydroxytryptamine （5-HT） content and an increase in corticosterone （CORT） content in the serum （P<0.05）. Compared with the model group， Tongxie Yaofang increased the 5-HT content and decreased the CORT content （P<0.05， P<0.01）. Compared with the normal group， the modeling increased the tumor volume and weight （P<0.05）， while Tongxie Yaofang inhibited such increases with no statistical significance. The tumor cells in the model group presented neat arrangement， irregular shape， uneven size， obvious atypia， common nuclear division， and small necrotic area， and blood vessels were abundant surrounding the tumor cells. Compared with the model group， Tongxie Yaofang groups showed sparse arrangement of tumor cells， different degrees of patchy necrosis areas in the tumor， and karyorrhexis， dissolution， and nuclear debris in the necrotic part. Compared with the normal group， the model group showed reduced CD49b-positive cells in the peripheral blood and tumor tissue （P<0.01）. Compared with the model group， Tongxie Yaofang increased CD49b-positive cells （medium dose P<0.01， high dose P<0.05， P<0.01）. Compared with the normal group， the modeling lowered the serum levels of granzymes-B （Gzms-B）， perforin （PF）， interferon （IFN）-γ， and tumor necrosis factor （TNF）-α （P<0.05， P<0.01）. Compared with the model group， low-dose Tongxie Yaofang elevated the serum levels of PF， Gzms-B， and TNF-α （P<0.05， P<0.01）， and medium-dose Tongxie Yaofang elevated the serum levels of Gzms-B， PF， IFN-γ， and TNF-α （P<0.05， P<0.01）. In addition， high-dose Tongxie Yaofang elevated the serum levels of PF， IFN-γ， and TNF-α （P<0.01）. Compared with the normal group， the model group presented down-regulated protein level of ULBP1 （P<0.05）. Compared with the model group， low-， medium-， and high-dose Tongxie Yaofang up-regulated the protein level of ULBP1 （P<0.05， P<0.01）， and medium- and high-dose Tongxie Yaofang up-regulated the protein level of MICA+MICB （P<0.05， P<0.01）. ConclusionTongxie Yaofang may promote NK cell activation by up-regulating the expression of MICA+MICB and ULBP1， thereby delaying the progression of colon cancer under chronic stress.

ObjectiveTo explore the effect and mechanism of Sishenwan-containing serum on aerobic glycolysis in human colon cancer HCT116 cells. MethodCell counting kit-8 （CCK-8） was used to detect the cell viability of colon cancer HCT116 cells after treatment with Sishenwan-containing serum （2.5%， 5%， and 10%） for 24， 48， 72 h. The concentration of lactic acid， the content of intracellular glucose， and the activity of hexokinase （HK） and fructose-6-phosphate kinase （PFK） in the cell culture medium were detected by the micro-method. The content of glucose transporter 1 （GluT1） mRNA was detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of GluT1 and methyltransferase-like 3 （MettL3） was detected by Western blot. The expression of GluT1 in cells was detected by immunofluorescence and the level of N6-methyladenosine （m⁶A） RNA methylation was detected by colorimetry. ResultCompared with the normal serum， 2.5%， 5%， and 10% Sishenwan-containing serum had no significant effect on the viability of HCT116 cells at 24 h， while 10% Sishenwan-containing serum showed a significant inhibitory effect on the viability of HCT116 cells at 48 h （P<0.05）. Hence， 10% Sishenwan-containing serum was used in subsequent experiments， and the intervention time was 48 h. Compared with the normal serum， 10% Sishenwan-containing serum could reduce lactate production （P<0.05）， down-regulate glucose uptake （P<0.05）， and blunt the activities of HK and PFK， the key rate-limiting enzymes of glycolysis （P<0.05）. Meanwhile， 10% Sishenwan-containing serum could decrease the expression of GluT1 protein （P<0.01） and mRNA （P<0.05） and reduce the proportion of cells expressing GluT1 （P<0.01）. Compared with the normal serum， Sishenwan-containing serum also decreased the protein content of MettL3 （P<0.05） and the methylation level of m⁶A RNA （P<0.01）. ConclusionSishenwan can inhibit glycolysis in colon cancer cells， and its inhibitory mechanism may be related to reducing MettL3 overexpression， inhibiting m⁶A RNA methylation， and down-regulating GluT1 and the activities of intracellular aerobic glycolysis-related enzymes such as HK and PFK.

Objective: To evaluate the application of artery first, combined vascular resection and reconstruction in the treatment of pancreatic head carcinoma. Methods: The clinical data of 13 patients with pancreatic head cancer were retrospectively analyzed from February 2014 to March 2016 in the Affiliated Hospital of Xiamen University. Preoperative computed tomography of high resolution layer or magnetic resonance imaging examination demonstrated pancreatic head carcinoma, as well as close adhesion, stenosis, compression or displacement of superior mesenteric vein or portal vein wall. In the operation, the artery first approach was used and the whole arterial blood supply in the head of the pancreas was fully exposed and interdicted. Finally, en block resection and vascular resection and reconstruction was adopted. Results: 12 of 13 patients had pancreatoduodenectomy synchronously with vascular resection and reconstruction; the other patient had these two surgery sequentially. Four patients received blood vessel wedge resection, five had segmental resection combined with end to end suture, and four had segmental resection combined with artificial vascular graft reconstruction. Operation time was (327.2±65.5) minutes, and the amount of blood loss was (472.6±226.4) millilitres. One patient suffered from delayed gastric emptying, and two patients had pancreatic fistula. All patients recovered from postoperative complications by conservative treatment. No patients developed biliary fistula, gastrointestinal fistula, abdominal infection, pulmonary infection, diarrhea, hypoglycemia or other complications, and none died in perioperative period. Postoperative pathological findings confirmed the diagnosis of pancreatic ductal adenocarcinoma. Mean tumor diameter was (4.2±1.5)cm, and (3.8±1.5) metastasis were found in (13.6±2.5) resected lymph nodes. In 11 cases, the tumor cells were found in the outer membrane of blood vessels, 2 cases were found to have tumor invasion in the inner membrane, and all the resection margins were negative. All patients were followed up, and 2 patients died of liver metastasis 11 months and 18 months after operation, respectively. One patient survived with local recurrence of tumor 13 months after surgery. Other patients had no tumor recurrence and metastasis. Conclusions The artery first approch combined vascular resection and reconstruction is safe effective and feasible in the treatment of pancreatic head carcinoma. It can improve the ablation rate of pancreatoduodenectomy.