Objective To investigate the distributions of vitamin K1 and K2 in infants of different age groups by comparing the serum levels of vitamin K1 and K2 in them.Methods 1177 infants from 0 to 3 months were divided into 6 age groups.Those born/treated in the subject units(pediatrics,neonatology,child health care,obstetrics)were selected as the study subjects and grouped by age:0～3 days(591 cases),4～7 days(255 cases),8～5 days(104 cases),1 month(118 cases),2 months(40 cases),and 3 months(69 cases).General data of the infants were collected,and the serum vitamin K1 and K2 levels were determined by HPLC-mass spectrometry(LC-MS)on a unified platform,and analyzed from the distribution of vitamin K1 and K2 at different ages.Results The distributions of vitamin K1 and K2 levels were statistically significant(P<0.001);newborns were highly vulnerable to vitamin K1 deficiency,and vitamin K2 deficiency was higher than vitamin K1 with age.Conclusion Maintaining the normal growth of vitamin K1 and K2 is crucial for the normal growth and development of infants of all ages,so we should pay close attention to the monitoring and supplement of vitamin K1 and K2.

Cholelithiasis is a common and frequent disease of the digestive system, and its incidence rate tends to increase with the improvement of living standards. Patients suffering from both gallbladder stones and common bile duct stones account for 5%-15%. Choledocholithiasis can cause a series of serious complications such as acute cholangitis and biliary pancreatitis. Choledocholithotomy is the main method for the treatment of choledocholithiasis, but there is still a high recurrence rate after surgery. The recurrence of choledocholithiasis seriously affects the life of patients and increases their economic burden. With reference to the latest published clinical studies, this article summarizes the influencing factors for the recurrence of choledocholithiasis from the aspects of anatomical factors, stone-related factors, biliary factors, and surgical factors, so as to provide a reference for the treatment of choledocholithiasis and the prevention of its recurrence.

ObjectiveTo investigate the effect of Qingre Lidan granules in preventing the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy through a retrospective cohort study. MethodsA total of 337 inpatients with choledocholithiasis （including those with cholecystolithiasis at the same time） who underwent laparoscopy combined with choledochoscopic lithotomy in The First Affiliated Hospital of Dalian Medical University from January 1， 2010 to December 31， 2020 were enrolled， and related clinical data were collected. According to the follow－up results， the patients were divided into exposure group （conventional treatment+Qingre Lidan granules） with 225 patients and non－exposure group （conventional treatment） with 112 patients. The recurrence of choledocholithiasis and the administration of Qingre Lidan granules were recorded in detail for both groups. The recurrence rate of choledocholithiasis and the time to recurrence were observed for both groups， and the risk factors for the recurrence of choledocholithiasis were analyzed. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann－Whitney U test was used for comparison of non－normally distributed continuous data between two groups； the chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan－Meier curve was used to estimate the cumulative probability of choledocholithiasis recurrence in the two groups， and the Log－rank test was used for comparison between two groups. ResultsA total of 26 patients experienced the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy， with 12 patients （5.33%） in the exposure group and 14 （12.5%） in the non－exposure group， and the exposure group had a significantly lower recurrence rate than the non－exposure group （χ²=5.394， P=0.020）. The exposure group had a significantly longer mean time to the recurrence of choledocholithiasis than the non－exposure group （40.1±26.7 months vs 19.2±13.5 months， t=2.383， P=0.017）. The Kaplan－Meier curve analysis showed that the non－exposure group had a significantly higher cumulative recurrence rate than the exposure group in different periods of time （P<0.05）. The multivariate logistic regression analysis showed that common bile duct diameter ≥14 mm （odds ratio 〔OR〕=2.935， P=0.031） and multiple calculi （OR=2.911， P=0.029） were independent risk factors for the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopic lithotomy. ConclusionQingre Lidan granules can effectively reduce the recurrence rate of choledocholithiasis and prolong the time to the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy and has a certain clinical effect in preventing the recurrence of choledocholithiasis after surgery.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

At present, acellular matrix is an effective replacement material for the treatment of skin damage, but there are few systematic evaluation studies on its performance. The experimental group of this study used two decellularization methods to prepare the matrix: one was the acellular matrix which sterilized with peracetic acid first (0.2% PAA/4% ethanol solution) and then treated with hypertonic saline (group A), the other was 0.05% trypsin/EDTA decellularization after γ irradiation (group B); and the control group was soaked in PBS (Group C). Then physical properties and chemical composition of the three groups were detected. Hematoxylin eosin (HE) staining showed that the acellular effect of group B was good. The porosity of group A and B were both above 84.9%. In group A, the compressive modulus of elasticity was (9.94 ± 3.81) MPa, and the compressive modulus of elasticity was (12.59 ± 5.50) MPa in group B. There was no significant difference between group A or B and group C. The total content of collagen in acellular matrix of group A and B was significantly lower than that of group C (1. 662 ± 0.229) mg/g, but there was no significant difference in the ratio of collagen Ⅰ/Ⅲ between group B and group C. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that there was no significant difference in microstructure. Qualitative detection of fibronectin and elastin in each group was basically consistent with that in group C. Therefore, acellular matrix of group B had better performance as scaffold material. The experimental results show that the acellular matrix prepared by γ-ray sterilization and decellularization of 0.05% Trypsin enzyme/EDTA could be used for the construction of tissue-engineered skin. It could also provide reference for the preparation and mounting of heterogeneous dermal acellular matrix. It was also could be used for electrostatic spinning or three-dimensional printed tissue engineered skin scaffold which could provide physical and chemical parameters for it.
Acellular Dermis ; Cells, Cultured ; Extracellular Matrix ; Porosity ; Tissue Engineering ; Tissue Scaffolds

Objective:To analyze the long-term prognosis of undergoing drug-eluting stent implantation (DES) or coronary artery bypass grafting (CABG) in patients with unprotected left main (ULM) coronary artery disease complicated with chronic renal failure (CRF).Methods:Patients with UML coronary artery disease complicated with CRF admitted to the department of cardiology intensive care unit (ICU) and cardiac surgery ICU of Beijing Anzhen Hospital Affiliated to Capital Medical University were enrolled. According to the estimated glomerular filtration rate (eGFR), the patients were divided into two layers, and the clinical characteristics of DES patients and CABG patients were analyzed. Log-Rank method and Cox regression were used to analyze the coronary artery disease and long-term clinical prognosis of patients with two surgical strategies.Results:A total of 353 patients were enrolled, including 150 patients with eGFR < 45 mL·min -1·1.73 m -2 (DES 67 cases, CABG 83 cases), eGFR 45-59 mL·min -1·1.73 m -2 in 203 cases (DES 80 cases, CABG 123 cases). In terms of demography and clinical history, compared with CABG group, DES group had lower proportion of complete revascularization and lower proportion of chronic totalocclusion (CTO) and multi vessel disease in each eGFR level. All patients were followed up for an average of (30.74±15.05) months. Log-Rank analysis showed that there was no significant difference in the incidence of major cardiovascular and cerebrovascular adverse events (MACCE), all-cause death, cardiogenic death and stroke between DES group and CABG group in each eGFR level. In eGFR 45-59 mL·min -1·1.73 m -2, the proportion of target vessel revascularization (TVR) in DES group was higher than that in CABG group (18.8% vs. 0.8%, P < 0.01); in eGFR < 45 mL·min -1·1.73 m -2, the incidence of myocardial infarction in DES group was higher than that in CABG group (10.4% vs. 1.2%, P < 0.05). Cox analysis showed that after adjusting for age, gender, history of hypertension, diabetes, left ventricular ejection fraction, smoking history, previous cerebrovascular disease, complete revascularization, multiple vessel disease and CTO, TVR proportion in DES group was still higher than that in CABG group in eGFR 45-59 mL·min -1·1.73 m -2 [hazard ratio ( HR) = 46.463, 95% confidence interval (95% CI) was 4.558-473.693, P = 0.001]; in eGFR < 45 mL·min -1·1.73 m -2, the incidence of myocardial infarction in DES group was still higher than that in CABG group ( HR = 14.098, 95% CI was 1.123-176.988, P = 0.040), there was no difference in TVR proportion between the two methods. Conclusions:eGFR < 45 mL·min -1·1.73 m -2 is an independent risk factor for DES in ULM patients. DES is safe and effective for ULM patients with CRF, but for patients with more severe CRF (eGFR < 45 mL·min -1·1.73 m -2), there was more myocardial infarction in DES group than that in CABG group, which should be carefully selected.

Objective To obtain methamphetamine concentration profiles in saliva and urine samples of drug addicts and to screen the colloidal gold strip. Methods Methamphetamine concentration in saliva and urine samples of drug addicts was determined by liquid chromatography tandem mass spectrometry. The initial screening was obtained by colloidal gold strip test. The results were compared and analyzed. Results using the method of protein and fluid MRM scan method to detect direct precipitation, saliva is linear in the range of 1~100ng/mL, the linear correlation coefficient is 0.9987, the detection limit is 0.1ng/mL, the limit of quantification was 1ng/mL, the urine is linear in the range of 1~100ng/mL, the linear correlation coefficient is 0.9943, the detection limit is 0.5ng/mL, the limit of quantification was 1ng/mL. Saliva and urine samples diluted, the concentration in the linear range. Saliva and urine samples of four types of methamphetamine colloidal gold reagent strip were screened directly, and the results were judged visually. Conclusion the detection rate of colloidal gold strip is about 79%, the detection rate of saliva is about 81%, and the detection rate can be increased to more than 93% by using two reagent strips. Combined with the initial screening results and the instrument confirmation concentration, it can be found that the gray zone setting and sensitivity setting have certain influence on the detection rate, and it is suggested to improve the sensitivity to meet the needs of screening.

Objective: To explore the inhibitory effect of icotinib combined with cytokine induced killer (CIK) on various human lung adenocarcinoma cell lines in vitro. Methods: The inhibitory effect of icotinib alone or icotinib combined with CIK on HCC827 and A549 cells was detected by cell counting kit-8(CCK-8). The apoptosis was detected by flow cytometry via Annexin V/PI staining. The effect of icotinib on CIK phenotype was detected by flow cytometry. Results: The inhibitory rates of HCC827 cells treated with 1.5, 3, 6, 12 μmol/L icotinib were (5.64±0.05)%, (8.62±0.45)%, (14.57±0.65)% and (18.52±0.91)%, respectively. The inhibitory rates of A549 cells were (1.64±0.48)%, (2.09±0.28)%, (3.69±0.45)%, (4.41±0.58)%, respectively. At the same concentration, the inhibitory rate of HCC827 cells with icotinib treatment was significantly higher than that of A549 cells (P<0.05). When the effector/target ratio was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells co-cultured with CIK were (15.17±2.33)%, (42.59±7.18)%, (62.59±8.95)%, respectively, and the inhibitory rates of A549 were(16.99±2.81)%, (46.31±1.89)%, (58.24±4.23)%, respectively. The inhibitory rate of HCC827 cells co-cultured with CIK was not significantly different from that of A549 cells at the same effector/target ratio (P_10∶1=0.299, P_20∶1=0.318, P_40∶1=0.366). When the effector/target ratio of CIK combined with 6 μmol/L icotinib was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells were (37.07±3.50)%, (76.03±6.55)%, (80.34±10.69)%, respectively, and the inhibitory rates of A549 cells were(25.72±1.41)%, (52.76±3.82)%, (62.26±1.94)%, respectively. The inhibitory rates of 6 μmol/L icotinib combined with CIK were significantly higher than those of icotinib group and CIK group alone at the same effector/target ratio (P<0.05), except for the effector/target ratio at 40︰1 on A549 cells (P=0.089). Moreover, all of the combination index (CI) of combined group were <1 (P<0.05). The apoptotic rates of HCC827 and A549 cells induced by icotinib combined with CIK were significantly higher than those of icotinib group and blank control group (P<0.05), especially the proportion of late apoptotic or necrotic cells.Increasing effector/target ratio of CIK contributed to stronger inhibition(P<0.05). The expressional rate of CIK phenotype with or without icotinib treatment was not significantly different from each other(P>0.05). Conclusions EGFR mutant lung adenocarcinoma cells are more sensitive to icotinib, while the EGFR mutation status has no effect on the killing effect of CIK cells. icotinib combined with CIK has a synergistic effect on the inhibition of tumor growth, and icotinib has no any impact on the phenotype of CIK cells.

Objective: To observe the predictive value of serial platelet function testing (PFT) on outcome in patients undergoing complex percutaneous coronary intervention (PCI). Methods: Six hundred and two consecutive patients undergoing complex PCI in Anzhen hospital were enrolled during October 2011 to June 2012.Adenosine diphosphate(ADP)-induced platelet aggregation was measured by light transmission aggregometry on the first, sixth and twelfth month after PCI and the mean value was calculated.The cut-off value of high on-treatment platelet reactivity (HTPR) was defined as 40%.The primary endpoint was major adverse cardiovascular and cerebral event (MACCE). Clinical outcomes were analyzed by the Kaplan-Meier method and differences were compared using the log-rank test.Multivariate analyses by Cox proportion hazards regression were applied to identify variables independently associated with the adverse outcomes. Results: Five hundred and eighty-five patients (HTPR, n=285; non-HTPR, n=280) finished the follow-up ((28.47±7.45) months). A total of 33 cases of MACCE were observed during the follow-up, among which 29 cases(8.42%) were in HTPR group and 9 cases (3.21%) in the non-HTPR group.Kaplan-Meier analysis suggested that HTPR was associated with an increased incidence of MACCE (log-rank test, P=0.01). The Cox multivariate analysis indicated that HTPR was an independent risk factor of MACCE (HR=2.69, 95%CI 1.23-5.85, P=0.01) in patients undergoing complex PCI.Incidence of MACCE was similar between HTRP patients receiving standard dual antiplatelet therapy (DAPT) or prolonged DAPT (>12 months). Conclusion Serial PFT could predict the long-term prognosis of patients underwent complex PCI.