BACKGROUND:Combination of biological and optical technique is used to study the molecular mechanism of cell proliferation and apoptosis, which has become the study hotspot in the filed of bioengineering.OBJECTIVE: The goal of this study was to study the molecular mechanism of XAP-induced apoptosis in single living human lung adenocarcinoma (ASTC-a-1) cells by using confocal fluorescence microscopy imaging and fluorescence resonance energy transfer (FRET) techniques.DESIGN: A controlled observation.SETTING: Institute of Laser Life Science (Key Laboratory of Education Department), South China Normal University.MARERIALS: This experiment was carried out in the Institute of Laser Life Science (Key Laboratory of Education Ministry), South China Normal University between October 2006 and March 2007. Human lung adenocarcinoma (ASTC-a-1) cells were cultured in our laboratory. Xiaoaiping (XAP) parenteral solution was purchased from Tonghua Shenyuan Pharmaceutical Co.,Ltd (No. Z20025869), and G418 was purchased from Huamei Biological Company. SCAT3 was provided by Professor Masayuki Miura. Auto microplate reader (infinite M200, Tecan,Austria)and mitochondrial location fluorescent probe (Mitertracker Red)was purchased from Molecular Probe Company.METHODS: ① The inhibition of XAP at different doses to ASTC-a-1 cell viability was detected by CCK-8. ② Dynamical change of caspase 3-induced by XAP was detected by confocal fluorescence microscopy imaging and fluorescence resonance energy transfer (FRET) techniques. ③The fluorescence emission spectrum of SCAT3 was detected by confocal fluorescence microscopy imaging at different time points after XAP treatment.MAIN OUTCOME MEASURES: ①Cell viability after XAP treatment. ② Dynamic change of fluorescence resonance energy transfer efficiency of SCAT3 detected after XAP treatment. ③ Dynamical change of mitochondrial morphology after XAP treatment.RESULTS: ①XAP inhibited the viability of tumor cells dose-dependently. ② XAP induced the activation of intracellular caspase 3. ③Some mitochondria became dot, and some were cracked after XAP treatment.CONCLUSION: XAP can induce the apoptosis of ASTC-a-1, and caspase 3 is involved in the regulation course.

Objective To investigate the expression of triggering receptor expressed on myeloid cells receptor-1 (TREM-1) in plasma and bronchoalveolar lavage fluid (BALF) and its correlation with Galactomannan,IFN,IL-6 and IL-10 in Aspergillus infected mice.Methods Cyclophosphamide (CTX) was intraperitoneally injected and fumigatus spore suspension was inhaled by nose to establish the immunocompromised invasive pulmonary aspergillosis (IPA) mouse model.Healthy controls,immunocompromised only and IPA only groups were also established.Each group had 6 mice.After inoculation,mice were sacrificed.Lung tissue specimens,BALF,and plasma samples were collected.Plasma and BALF soluble TREM-1 (sTREM-1),Galactomannan,IFNγ,IL-6,and IL-10 were detected by ELISA.Results Positive Aspergillus fumigatus was found by tissue culture in the lung.Infiltration of inflammatory cells,blood congestion and interstitial lung tissue injury were observed in histological sections of both IPA and immunocompromised IPA mice.Compared to IPA group [(453.78 ± 74.18) ng/L,P ＜ 0.001;(10.21±1.46) ng/L,P＜0.001] and control group [(245.16 ±65.85) ng/L,P＜0.001;(6.60 ± 3.74) ng/L,P ＜ 0.001],the plasma and BALF sTREM-1 significantly increased in immunocompromised IPA group [(1 537.64 ± 359.52) ng/L;(20.12-± 2.72) ng/L].Compared to control group,both the BALF sTREM-1 in IPA group (P =0.041) and the plasma and BALF Galactomannan,IFNγ,IL-6,and IL-10 levels in IPA and immunocompromised IPA groups were significantly higher (P ＜0.01).Pearson correlation analysis showed that plasma and BALF sTREM-1 were significantly correlated with Galactomannan (r =0.83,P ＜ 0.001;r =0.82,P ＜ 0.001),IFNγ (r =0.79,P＜0.001;r=0.61,P＜0.01),IL-6 (r=0.81,P＜0.001;r=0.66,P＜0.01),andIL-10 (r=0.70,P =0.001;r =0.54,P =0.02).Conclusions Plasma and BALF sTREM-1 appears highly expressed in Aspergillus infected mice.sTREM-1 in mice plasma and BALF is closely correlated with Galactomannan,IFNγ,IL-6,and IL-10 levels,which suggests that sTREM-1 has great diagnostic value during invasive fungal infection.

Objective:To investigate the infarct size and its related factors in patients with anterior choroidal artery (AchA) territory infarction.Methods:From April 2016 to April 2018, consecutive patients with acute AchA territory infarction hospitalized in the Department of Neurology, the Affiliated Shuyang Hospital of Xuzhou Medical University were enrolled retrospectively. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of the disease at baseline, and the Diffusion-Weighted Imaging (DWI) was used to determine the side, location, size, and morphology of the infarct lesions. The patients were divided into small infarction group (<20 mm) and large infarction group (≥20 mm). Multivariate logistic regression analysis was used to determine the independent risk factors for infarct size. Results:A total of 100 consecutive patients with acute AchA territory infarction were enrolled, including 86 (86.0%) in small infarction group, 14 (14.0%) in large infarction group. Based on the NIHSS score, there were 89 patients with mild stroke, 9 with moderate stroke, and 2 with severe stroke. According to DWI, 69 patients (69.0%) had long cord-like infarcts and 31 (31.0%) had other shapes of infarcts. The baseline NIHSS score (7.0 [2.0-10.5] vs. 3.0 [2.0-4.0]; Z=2.353, P=0.019) and the proportion of patients with severe stroke (14.3% vs. 0%; P=0.018), the infarcts in posterior part of periventricular area (85.7% vs. 57.0%; χ2=4.180, P=0.041) and medial globus pallidus (21.4% vs. 4.7%; χ2=5.206, P=0.023), and cord-like infarction (92.9% vs. 65.1%; χ2=4.332, P=0.037) in patients of the large infarction group were significantly higher than those of the small infarction group; leukocyte count (7.7±1.7×10 9/L vs. 6.6±1.8×10 9/L; t=2.214, P=0.036) and platelet count (234.5±39.5×10 9/L vs. 198.0±49.4×10 9/L; t=2.618, P=0.010) were significantly higher than those of the small infarction group; the proportion of patients with sensory impairment was significantly higher than that of the small infarction group (50.0% vs. 24.4%; χ2=3.908, P=0.048). Multivariate logistic regression analysis showed that platelet count (odds ratio 1.018, 95% confidence interval 1.000-1.621; P=0.044) and stroke severity (odds ratio 18.245, 95% confidence interval 1.534-217.052; P=0.022) were significantly and positively correlated with the infarct size. Conclusion:The related factors of the infarct size in patients with AchA territory infarction included sensory impairment, baseline NIHSS score, stroke severity, morphology and location of infarct lesions, and leukocyte and platelet counts, of which platelet count and stroke severity were independently positively correlated with the infarct size.

Objective:To explore the clinical features and pathogenic causes of a Chinese Han family with Wagner syndrome, and to analyze the relationship between VCAN gene mutation and patient phenotype. Methods:The method of family pedigree investigation was adopted.A Chinese Han family with Wagner syndrome in 3 generations including 13 family members was collected in Xiamen Eye Center of Xiamen University in January 2020, and 5 patients from 3 generations were diagnosed.All members underwent a comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, intraocular pressure, slit lamp microscopy, and ophthalmoscopy to analyze the condition of anterior segment and fundus.Anterior segment photography, fundus photography, optical coherence tomography and ultrasound biological microscopy were carried out in the proband and some patients to analyze the condition of anterior segment, fundus and anterior chamber angle.The peripheral venous blood of all family members was collected for genomic DNA extraction, and pathogenic gene variation analysis for verification was through high-throughput target region capture sequencing and Sanger sequencing.Variants were scored using the American College of Medical Genetics and Genomics (ACMG) guidelines, and the structure and function of variants were predicted through PredictProtein.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.MR-35-22-002800).Written informed consent was obtained from each subject.Results:The Chinese pedigree with Wagner syndrome was in accordance with autosomal dominant inheritance pattern, and all patients had no history of systemic disease or other abnormal manifestations.The common ophthalmic features of the patients were abnormal suspensory ligament, premature cataract, vitreous cavity, vitreous condensation, veil-like proliferative membrane in the vitreous cavity, retinal choroid atrophy and thinning, tractional retinal detachment, and retinal pigmentation.The proband had binocular cataract surgery, and binocular intraocular lens dislocation occurred after the operation.Genetic analysis revealed that a heterozygous splice site variation c.9265+ 1G>A in the VCAN gene in this family was co-segregated with the disease phenotype and graded as a likely pathogenic variant by the ACMG guidelines.This variant base pair substitution could cause the formation of a protein product with 1 754 amino acids shorter, resulting in insufficient haploid dosage and severe reduction of glycosaminoglycan attachment sites, making the versican protein dysfunctional. Conclusions:It is the first time to report a Chinese family with Wagner syndrome in China, and it is confirmed that the family has a heterozygous variation in the VCAN gene c.9265+ 1G>A by molecular genetic analysis.

Objective To discuss the application of gelatin sponge-hemocoagulase plugging agent in patients with pulmonary puncture bleeding.Methods The clinical data of 43 patients with hemorrhage caused by DSA-guided lung puncture biopsy,who received gelatin sponge-hemocoagulase plugging agent treatment at the Jining Municipal First People's Hospital of China between September 2021 and May 2023,were collected,and the hemostatic effect of gelatin sponge-hemocoagulase plugging agent was analyzed.Results Successful lung puncture needle biopsy was achieved in all the 43 patients.The puncture needle channel occlusion was accomplished by using gelatin sponge-hemocoagulase plugging agent.Five minutes after occlusion treatment,in one patient,whose moderate hemoptysis with moderate bleeding shadow before puncture needle biopsy changed to bloody sputum,the intrapulmonary bleeding shadow displayed on image became slightly enlarged when compared the size five minutes ago,while in all the remaining patients successful hemostasis was achieved,the hemoptysis disappeared and the pulmonary hemorrhage shadow was similar to that five minutes ago.No occlusion-related complications occurred in all patients.Conclusion For the treatment of pulmonary hemorrhage caused by DSA-guided lung puncture biopsy,gelatin sponge-hemocoagulase plugging agent is clinically safe and effective.

Objective To discuss the application value of XperCT combined with needle-guided Glubran-2 glue for small pulmonary nodule localization in thoracoscopic pulmonary nodule resection.Methods The clinical data of 67 patients,who received XperCT combined with needle-guided Glubran-2 glue for small pulmonary nodule localization before thoracoscopic resection of a single small pulmonary nodule at the Jining Municipal First People's Hospital of China between June 2018 and February 2023,were retrospectively analyzed.The size of the pulmonary nodule,the maximum vertical distance from the visceral pleura to the lesion,the technical success rate of localization,the number of puncturing times,the complications,the time spent for operation,and the postoperative pathological diagnosis were recorded.Results The average size of the small pulmonary nodules in the 67 patients was 8.7 mm,and the average vertical distance from the visceral pleura to the lesion was 19.4 mm.Successful preoperative localization of nodule was accomplished in all patients.The average number of puncturing times was 1.1,and no serious complications occurred.The average time spent for operation was 12.7 min.Definite pathological results were obtained in all 67 patients.Conclusion XperCT combined with needle-guided Glubran-2 glue for small pulmonary nodule localization carries advantage of accurate localization with fewer complications.Therefore,this technique is a highly-efficient and quickly-accomplished positioning method,and it is highly valuable in clinical practice.(J Intervent Radiol,2024,33:623-626)

Objective To observe the effect of transcatheter arterial embolization(TAE)with Glubran-2 glue for treating hemorrhage after percutaneous transhepatic cholangial drainage(PTCD).Methods Data of 17 patients with hemorrhage after PTCD who underwent TAE with Glubran-2 glue were retrospectively analyzed.The technical success rate,clinical success rate and complications were observed.The red blood cell(RBC)and hemoglobin(Hb)on the day of TAE and the next day of TAE were compared,also the glutamic-pyruvic transaminase(GPT)level before TAE,on the next day of TAE,on the second and the fourth day after TAE,respectively.Results The offending vessel of bleeding was successfully embolized in all 17 cases,both technical success rate of TAE and clinical success rate of hemostasis were 100%.There was no serious complication such as liver abscess,septicemia nor pulmonary embolism.No significant difference of RBC nor Hb was found between the day of TAE and the next day of TAE(both P＞0.05).GPT before TAE was lower than the next day of TAE and the second day after TAE(P＜0.05),while no significant difference of GPT was found before TAE and 4 days after TAE(P＞0.05).Conclusion TAE with Glubran-2 glue for treating hemorrhage after PTCD was safe and effective.

Objective To evaluate the prognostic value of arterial blood lactate clearance based on central venous oxygen saturation and perfusion index in patients with septic shock related myocardial injury after early goal-directed therapy.Methods One hundred and fifty-seven patients with septic shock after early resuscitation were enrolled from August 2013 to July 2016 in ICU at Peking Union Medical College Hospital.Parameters indicating early resuscitation included central venous pressure (CVP) 8-12 mmHg (1 mmHg=0.133 kPa),mean arterial pressure (MAP)＞65 mmHg,central venous oxygen saturation(ScvO2)＞70％ and urine volume (UO) ＞0.Sml · kg-1 · h-1 and arterial blood lactatc (Lac) ＞2 mmoL/L.Patients were divided into group A [ScvO2＞80％ and perfusion index (PI)＞1.4],group B(ScvO2＞80％ and PI＜1.4),group C (ScvO2＜80％ and PI＞1.4),group D(ScvO2＜80％ and Pl＜l.4).Hemodynamic parameters and tissue perfusion indexes at 2 hours(T2),4 hours(T4) and 6 hours(T6) after early resuscitation and troponin Ⅰ which indicated myocardial damage,on day 1 2 3 in ICU were recorded.Results (1)Lac clearance in group C was the quickest,which was 34.57％ (21.44％,44.20％),58.33％ (30.19％,70.79％),71.43％ (53.75％,82.79％) at T2,T4,T6 respectively.(2)The maximal incidence of myocardial damage was in group B(85.0％) and the lowest in group A (45.7％) on day 1 in ICU.Whereas on day 2,group C showed the lowest incidence of myocardial damage (29.3％) and group B the highest(70.0％).On day 3,the proportion of elevated troponin Ⅰ in group B was 70.0％,which was significantly higher than that of group B (29.3％,P＜0.008).(3)Logistic regression analysis suggested that the rate of Lac clearance at T4 in group B was related to the incidence of myocardial damage on day 2 and 3 in ICU.Conclusions The combination of PI and ScvO2 as a resuscitation target in patients with septic shock facilitates Lac clearance as the goal of resuscitation.The rate of arterial Lac clearance based on ScvO2 and PI is correlated with myocardial injury in patients with septic shock after early goal-directed therapy.

Objective:To investigate the clinical characteristics of first-episode and recurrent acute hypertriglyceridemic pancreatitis (HTGP).Methods:The retrospective cohort study was con-ducted. The clinical data of 313 patients with HTGP admitted to 26 medical centers in China in the Chinese Acute Pancreatitis Clinical Research Group (CAPCTG)-PERFORM database from November 2020 to December 2021 were collected. There were 219 males and 94 females, aged 38(32,44)years. Of the 313 patients, 193 patients with first-episode HTGP were allocated into the first-episode group and 120 patients with recurrent HTGP were allocated into the recurrent group. Observation indica-tors: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of severity and prognosis in the course of disease within 14 days between the two groups; (3) the association between recurrent HTGP and the risk of persistent organ failure (POF); (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve and Log-Rank test was used for survival analysis. The Logistic regression model was used for multivariate analysis, and continuous variables were converted into categorical variables according to the mean value or common criteria. Propensity score matching was performed by 1∶1 nearest neighbor matching method, with caliper value of 0.02. Paired t test or Wilcoxon rank sum test and McNemar′s test were used for comparison between matched groups. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 313 patients,208 cases were successfully matched, including 104 cases in the first-episode group and 104 cases in the recurrent group. After propensity score matching, there was no significant difference in demographic characteristics, severity of illness scores and laboratory test between the two groups ( P>0.05). The elimination of gender, acute physiology and chornic health evaluation (APACHE) Ⅱ score, computed tomography severity index score, systemic inflammatory response syndrome score, sequential organ failure assessment score, apolipoprotein E, C-reactive protein, creatinine, lactic acid dehydrogenase, procal-citonin confounding bias ensured comparability between the two groups. (2) Comparison of severity and prognosis in the course of disease within 14 days between the two groups. There were signifi-cant differences in POF and local complications between the first-episode group and the recurrent group ( P<0.05). (3) The association between recurrent HTGP and the risk of POF. Results of uncor-rected univariate analysis showed that there was no association between recurrent HTGP and the risk of POF ( odds ratio=0.78, 95% confidence interval as 0.46-1.30, P>0.05). Results of multivariate analysis after adjusting for covariates such as gender, age, APACHE Ⅱ score, C-reactive protein, triglyceride and total cholesterol showed that compared with first-episode HTGP, recurrent HTGP was associated with a higher risk of POF ( odds ratio=2.22, 95% confidence interval as 1.05-4.71, P<0.05). Results of subgroup analysis showed that age<40 years was associated with an increased risk of POF ( odds ratio=3.31, 95% confidence interval as 1.09-10.08, P<0.05). (4) Follow-up. Twelve of the 313 patients died during hospitalization, including 9 cases in the first-episode group and 3 cases in the recurrent group. The rest of 301 surviving patients, including 184 cases in the first-episode group and 117 cases in the recurrent group, were followed up for 19.2(15.5, 21.9)months. Results of follow-up showed that for 184 survived patients of the first-episode group, 164 cases were followed up and 24 cases experienced recurrence, for 117 survived patients of the recurrent group,29 cases experienced recurrence, showing a significant difference between the two groups ( χ2=4.67, P<0.05). Conclusion:Compared with first-episode HTGP, patients with recurrent HTGP are more prone to POF and local complications, and are more prone to recurrence after discharge. The risk of POF in recurrent HTGP patients is 2.22 times that of those with first-episode, and the risk is higher in patients with age <40 years.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.