Objective:To observe the distribution characteristics of fungi, bacteria and Demodex in the eyelid margin of patients with blepharitis and without blepharitis at different ages. Methods:A cross-sectional study was conducted.A total of 98 patients diagnosed with anterior blepharitis and 99 patients diagnosed with posterior blepharitis in Henan Eye Hospital from March 2021 to June 2022 were enrolled as anterior blepharitis group and posterior blepharitis, respectively.Additionally, 100 patients with an initial diagnosis of refractive error and 200 patients with vitreous opacity were enrolled during the same period as a non-blepharitis group.All patients underwent examinations for lid margin fungi, bacteria and eyelash Demodex, as well as fungal spores and ciliary Demodex count.The differences in the positive rate and load of palpebral fungi, bacteria and eyelash Demodex were compared between anterior and posterior blepharitis groups, as well as across different ages in non-blepharitis group.This study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[18]).All patients were informed about the purpose and methods of the study.Written informed consent was obtained from each patient. Results:There were significant differences in the positive rates of bacteria, fungi and Demodex and the load of Demodex in the non-blepharitis group at different ages ( χ2=28.34, 10.36, 51.57, H=35.66; all at P<0.01).The positive rates of palpebral bacteria and ciliary Demodex and the load of Demodex were significantly higher and the palpebral fungi positive rate was significantly lower in the ≥60 years old than in the <60 years old (all at P<0.05).There were significant differences in the positive rates of bacteria and fungi among anterior blepharitis, posterior blepharitis and non-blepharitis groups ( χ2=18.99, 6.36; all at P<0.01).The palpebral bacteria positive rate was significantly higher in anterior blepharitis group than in posterior blepharitis and non-blepharitis groups, and the palpebral fungi positive rate was significantly higher in anterior blepharitis and posterior blepharitis groups than in non-blepharitis group (all at P<0.05).There was no significant difference in the ciliary Demodex detection rate among the three groups ( χ2=0.16, P=0.74).The number of palpebral fungi spores and eyelash Demodex counts were higher in anterior and posterior blepharitis groups than in non-blepharitis group, and the differences were statistically significant (all at P<0.05).The positive rate of palpebral margin bacteria in ciliary Demodex-positive group was 45.7%(156/341), which was significantly higher than 25.6%(40/156) in ciliary Demodex-negative group ( χ2=17.20, P<0.01), and there was no significant difference in the positive rate of palpebral margin fungi between them ( χ2=0.11, P=0.70). Conclusions:In the population with normal eyelid margin, the infection of Demodex and bacteria in lid margin increases and fungal infection decreases in the ≥60 years old.Fungal and bacterial infections are the main sources of palpebral infection in patients with blepharitis, and positive detection of Demodex increases the chance of bacterial infection.

Lipocalin-2 (LCN2) is a secreted glycoprotein originally purified from mouse kidney cells infected with simian virus 40 and plays a key role in the control of cellular homeostasis during inflammation and the response to cellular stress or injury, and it is considered a potential biomarker for rheumatic diseases, cancer, liver diseases, and inflammatory diseases. Studies have shown that LCN2 is expressed in hepatic parenchymal and nonparenchymal cells and is secreted into the bloodstream, and it is closely associated with the development and progression of acute liver injury, liver cirrhosis, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. This article summarizes the animal experiments and clinical studies on the association of LCN2 with the pathogenesis of liver diseases, in order to provide new ideas and therapeutic targets for the prevention and treatment of liver diseases.

Objective:To investigate the clinicopathological features of missed synchronous multiple early gastric cancer (SMEGC).Methods:Clinical and pathological data of 10 missed SMEGC patients in Beijing Friendship Hospital collected from January 2015 to December 2019 were reviewed for the clinicopathological and endoscopic features.Results:Ten missed SMEGC patients were all over 60 years old, and 6 of them were males. Six patients had family history of tumor and 6 had comorbidity (hypertension, diabetes, dyslipidemia, cardiovascular or cerebrovascular diseases). In terms of endoscopic and pathological manifestations, missed lesions of 6 cases were not smaller than the initial lesions, and more than half of the missed lesions had the same vertical location in the stomach (6/10), infiltration depth (8/10), histological classification (9/10), atrophic (8/10) and intestinal metaplasia (8/10) as the initial lesions.Conclusion:Physicians should be aware of the possibility of missed lesions during the first endoscopic treatment and the follow-up, especially at the same vertical location of the initial lesions in elderly males with family history of tumor and comorbidity.

Objective:To compare the early and late predictive values of critical illness score (CIS) and procalcitonin (PCT) in septic patients with blood stream infection (BSI) induced by intra-abdominal infection (IAI), and to identify the value of PCT in etiological diagnosis.Methods:The clinical data of patients with at least one positive blood culture within 24 hours admission to the emergency department of China-Japan Friendship Hospital from January 2014 to December 2019 and with final diagnosis of IAI induced sepsis were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) scores were calculated based on the parameters on the day of admission. Differences in various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28 days or 60 days were compared. Receiver operator characteristic curve (ROC curve) was used to analyze the value of PCT in differential etiological diagnosis of IAI induced sepsis caused by single bacterial infection, and the predictive value of CIS and PCT on 28-day and 60-day death of septic patients with BSI induced by IAI.Results:A total of 221 septic patients with IAI caused by single bacterial infection were enrolled. The 28-day mortality was 19.9% (44/221), and the 60-day mortality was 25.8% (57/221). Mortality caused by Gram-positive (G +) bacterial infection of patients was significantly higher than that caused by Gram-negative (G -) bacterial infection (28 days: 34.6% vs. 11.4%, 60 days: 42.0% vs. 16.4%, both P < 0.01). Compared with patients with G + bacterial infection, the PCT value of patients with G - bacterial infection was higher [μg/L: 4.31 (0.71, 25.71) vs. 1.29 (0.32, 10.83), P < 0.05]. Compared with survival group, the values of CIS and PCT in death group were higher, either in 28 days or in 60 days [death group vs. survival group in 28 days: SOFA score was 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 11 (9, 14) vs. 6 (6, 9), LODS score: 4.0 (2.0, 6.0) vs. 1.0 (0, 2.0), APACHEⅡ score: 17.0 (15.0, 24.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 3.48 (1.01, 26.70) vs. 2.45 (0.32, 15.65); death group vs. survival group in 60 days: SOFA score: 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 9 (6, 14) vs. 6 (6, 9), LODS score: 4.0 (1.0, 5.0) vs. 1.0 (0, 2.0), APACHEⅡ score: 16.5 (12.0, 20.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 2.67 (0.98, 17.73) vs. 2.22 (0.31, 16.75); all P < 0.05]. ROC curve showed that: ① the area under ROC curve (AUC) of PCT in the diagnosis of IAI induced sepsis with single bacterial infection was 0.740 [95% confidence interval (95% CI) was 0.648-0.833]. When the optimal cut-off value of PCT was 1.82 μg/L, the sensitivity of diagnosis of G - bacterial infection was 74.0%, and the specificity was 68.2%. When PCT value was higher than 10.92 μg/L, the specificity of diagnosis of G - bacterial infection could reach 81.8%. ② In the prediction of 28-day and 60-day mortality for septic patients with BSI induced by IAI, the APACHEⅡ score achieved the highest AUC [28 days: 0.791 (95% CI was 0.680-0.902), 60 days: 0.748 (95% CI was 0.645-0.851)]. APACHEⅡ score higher than 14.5 could help to predict 28-day and 60-day mortality for IAI patients with negative predictive values of 94.9% and 88.5%. However, the predictive value of PCT for septic patients with BSI induced by IAI was relatively lower [28-day AUC: 0.610 (95% CI was 0.495-0.725), 60-day AUC: 0.558 (95% CI was 0.450-0.667)]. Conclusion:PCT is more reliable in the identification of pathogen type among IAI induced sepsis with BSI, while APACHEⅡ score may perform better in predicting early and late mortality.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Objective:To evaluate the accuracy of serum concentration of procalcitonin (PCT) in differential diagnosis of the etiology of bloodstream infections (BSI).Methods:Patients hospitalized in ICU of China-Japan Friendship Hospital from January 2015 to June 2020 with BSI and with PCT test simultaneously when blood drawing for blood culture were enrolled. Sequential Organ Failure Assessment (SOFA) were calculated based on parameters on the day of blood culture. Difference of various indicators among different pathogen infections were compared. Receiver Operating Characteristic (ROC) Curve was used to analyze the value of PCT in differential diagnosis of BSI by different pathogens.Results:Among 1 456 patients with BSI,1 261 (86.6%) patients with monobacterial infection, 80 (5.5%) patients with candidiasis and 115 (7.9%) patients with mixed infection. The 28-day mortality was 24.5% (356/1 456) and the 60-day mortality was 30.6% (446/1456). Mortality of both 28-day and 60-day in the mixed group was significantly higher than that in the bacteriacemia group and candidemia group. PCT levels was significantly higher in patients with bacteremia caused by gram-negative bacteria (GNB) than that in gram-positive bacteria (GPB) infected bacteremia and candidemia {3.4 μg/L[95% confidence interval (95% CI) 0.7-17.0 μg/L] vs 1.3 μg/L (95% CI 0.4-7.3 μg/L); 3.4μg/L (95% CI was 0.7-17.0 μg/L) vs 1.1 μg/L (95% CI was 0.4-3.4 μg/L); P<0.01} . ROC curve analysis showed that: ① the optimal cut-off value of PCT in differential diagnosis of monobacterial bacteremia and candidemia was 7.25 μg/L, with specificity of 90.0% and the area under the ROC curve (AUROC) was 0.612 (95% CI 0.533-0.691). When PCT value was greater than 0.51 μg/L, the sensitivity of diagnostic of bacteremia could reach 73.3%. ② the optimal cut-off value of PCT in differential diagnosis of bacteremia caused by GNB infection and candidemia was 7.32 μg/L, with specificity of 90.0% and AUROC was 0.695 (95% CI 0.614-0.776). When PCT value was greater than 0.51 μg/L, the sensitivity of diagnostic of bacteremia caused by GNB infection was 84.9%.③ the optimal cut-off value of PCT in differential diagnosis of bacteremia caused by GNB and GPB infection was 0.52 μg/L, with sensitivity of 84.9% and AUROC was 0.713 (95% CI 0.672-0.755). When PCT value was greater than 7.36 μg/L, the specificity of diagnostic of bacteremia caused by GNB infection could reach 80.1%. Conclusions:PCT can provide additional information about the possible etiology of patients with BSI, especially as high levels often indicate the possibility of GNB bacteremia.

Objective:To study the antimicrobial activity of diacerein on common pathogens of the ocular surface in vitro.Methods:Pathogens were collected from patients with ocular surface infections in Henan Eye Hospital, including Gram-positive cocci and bacilli, Gram-negative bacilli, filamentous fungi, and Candida.The antimicrobial activity of diacerein was determined by the K-B agar diffusion method, and its minimum inhibitory concentration (MIC) was determined by the micro-liquid method.Levofloxacin and voriconazole were used as the control of antibacterial and antifungal drug, respectirely.Results:Diacerein showed antibacterial activity against 42 strains of Gram-positive cocci and 10 strains of Gram-positive bacilli, its inhibition zone diameters for Staphylococcus epidermidis, S.aureus, S.intermedius and Gram-positive Corynebacterium were not significantly different from those of levofloxacin (all at P>0.05). Its MIC range of diacetate against Staphylococcus epidermidis, S. aureus, S. intermedius and other Staphylococci was 1-32 μg/ml, and its respective MIC 90 was 16, 8, 16, and 32 μg/ml.Diacerein had no bacteriostatic effect on 23 strains of Gram-negative bacilli, 10 strains of filamentous fungi and 3 strains of candida. Conclusions:Diacerein has antibacterial effects against Gram-positive Staphylococcus and Corynebacterium isolated from the ocular surface, but shows no antimicrobial activity against Gram-negative bacilli and fungi.Diacerein offers a new drug option and method for the treatment of bacterial keratitis.

Objective:To compare the early and late predictive value of several critical illness scores (CISs) and biomarkers in patients with bloodstream infection (BSI)-associated pneumonia, and to identify the value of procalcitonin (PCT) in etiological diagnosis.Methods:Patients with at least one positive blood culture within 24 hours admission to department of emergency of China-Japan Friendship Hospital from January 2014 to December 2018 and with final diagnosis of pneumonia were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluationⅡ (APACHEⅡ) scores were calculated based on the first parameters on the day of admission. Differences of various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28-day or 60-day were compared. Receiver operating characteristic (ROC) curve was used to analyze the value of biomarkers in differential diagnosis of pneumonia caused by single bacterial infection, and the predictive value of several CISs and biomarkers on 28-day and 60-day death of patients with pneumonia.Results:Among 540 patients with pneumonia caused by single bacterial infection, 256 (47.4%) patients with Gram-positive bacteria (GPB) infection and 284 (52.6%) with Gram-negative bacteria (GNB) infection. The 28-day mortality was 29.4% (159/540) and the 60-day mortality was 36.3% (196/540). PCT level was significantly higher in patients with GNB infection than that in GPB infected patients [μg/L: 1.99 (0.32, 13.19) vs. 0.45 (0.13, 3.53), P < 0.01]. There were significant differences of CISs and biomarkers between death group and survival group in predicting 28-day and 60-day mortality in BSI-associated pneumonia. ROC curve analysis showed that: ① the optimal cut-off value of PCT in the diagnosis of single bacterial infection was 0.48 μg/L, with the area under ROC curve (AUC) was 0.739 [95% confidence interval (95% CI) was 0.686-0.793]. When PCT value was greater than 4.49 μg/L, the specificity of diagnostic of GNB infection could reach 81.8%, and the positive predictive value (PPV) was 75.0%. When PCT value was greater than 10.16 μg/L, the diagnostic specificity could reach 91.2%. ② In the prediction of 28-day and 60-day mortality, the SOFA score showed highest AUC [28-day: 0.818 (95% CI was 0.768-0.867), 60-day: 0.800 (95% CI was 0.751-0.849)]. SOFA score greater than 8.5 points could help to predict 28-day and 60-day mortality for pneumonia patients with specificity of 90.5% and 91.6%, respectively. AUC of PCT for predicting 28-day and 60-day mortality in patients with BSI associated with pneumonia was 0.637 (95% CI was 0.575-0.700) and 0.628 (95% CI was 0.569-0.688), respectively. When PCT value was greater than 8.15 μg/L, the specificity and negative predictive value (NPV) were 80.2% and 75.1% respectively, and they could reach 80.2% and 68.7% when PCT value was greater than 7.46 μg/L. Conclusion:PCT is more reliable in the identification of pathogen type in BSI-associated pneumonia, while CISs may be more advantageous in the assessment of early and late prognosis.

Objective To analyze the possible influencing factors of postoperative bleeding after endoscopic submucosal dissection and endoscopic mucosal resection ( ESD/EMR) for early gastric cancer. Methods Clinical data of patients receiving ESD/EMR for the diagnosis of early gastric cancer at the Endoscopy Center of Beijing Friendship Hospital from January 2013 to May 2018, including demographic information ( age, gender and history ) , endoscopic lesion characteristics ( tumor size, location and morphology) and postoperative pathological features ( differentiated types and invasive depth) were collected to analyze the effects of these factors on bleeding after ESD/EMR. Results A total of 195 patients with early gastric cancer were included in the study and 9 cases ( 4. 6％) had postoperative bleeding. The medication history of clopidogrel and main lesion sizes were statistically different between postoperative bleeding group and non-bleeding group ( P=0. 018 and P=0. 034 ) . Multivariate analysis showed a history of clopidogrel ( OR=10. 223, 95％CI:1. 143-91. 468, P= 0. 038 ) , multiple lesions ( OR= 6. 412, 95％CI:1. 123-36. 616, P=0. 037) and lesions sizes of larger than 2 cm ( OR=6. 718, 95％CI:1. 130-39. 935, P=0. 036) were possible risk factors for postoperative bleeding. Survival analysis showed of higher postoperative bleeding risks in patients with the history of clopidogrel ( P<0. 001) and lesions sizes of more than 2 cm ( P=0. 022) . Conclusion More attention should be paid to the risk of ESD/EMR postoperative bleeding in early gastric cancer patients with medication history of clopidogrel and multiple large lesions.

Objective To investigate the imaging manifestations of different filamentous fungal strains under the confocal laser scanning microscope and slit-lamp microscope,and evaluate the feasibility of rapid diagnosis and therapeutic efficacy judgment for fungal culture negative patients.Methods A diagnosis trail was performed.Nine hundred and ninety-three patients with fungal keratitis (FK) which were varified by fungal culture were included in Henan Eye Hospital from September 2013 to January 2014.Distribution of fungi strains and positive rate of fungal strains by fungal culture and corneal confocal laser scanning microscopy were compared.The imaging characteristics of different filamentous fungi and different stages of one filamentous fungi under the slit-lamp microscope and confocal laser scanning microscopy were summarized.Results In the 993 FK patients,the diagnostic positive rate of fungal culture and confocal laser scanning microscopy was 43.20％ and 82.07％,respectively,showing a significant difference between them (x2 =45.323,P =0.000).In 429 culture-positive patients,the diagnostic positive rate of confocal laser scanning microscopy was 92.31％;while in 564 culture-negative patients,the diagnostic positive rate of confocal laser scanning microscopy was 74.29％.In 429 culture-positive patients,Aspergillus was the most common genus,accounting for 50.12％,and followed by Fusarium sp.and Altemaria sp.(18.18％ and 10.49％).There were no significant differences in fungal species distributions between fungal culture and confocal laser scanning microscopy examination in 429 cases (all at P＞0.05).The imaging characteristics under the slit-lamp microscope and confocal laser scanning microscope were different in different fungi stains.Aspergillus infection showed a plume-like corneal ulcer,and the Aspergillus sp.hyphae were thin and line-shaped with high reflective light and less branched under the confocal laser scanning microscope.Toothpaste-like corneal infiltration was seen in Fusarium sp.-infectious lesions under the slit lamp microscope,and mycelium showed a high-reflective long rod-like image with less branch in the image of confocal laser scanning microscope.Alternaria alternate sp.corneal infection showed nevus lesions,and hyphae characterized by high-reflective long rod or string beads in shape with less branches in the image of confocal laser scanning microscope.The mycelium was ruptured,shorter,thinner with weak reflective light following drug therapy.The differential diagnosis could be easily obtained between hyphae and corneal nerve fibers by confocal laser scanning microscope.Hyphae intertwined,or had branches with diffuse distribution,which surrounded by highreflective inflammatory cells and destructed matrix fiber and were located in stroma.The corneal nerve fibers located between epithelium layer and stroma layer,surrounded by normal epithelium or stroma structure.The diameter of the thicker nerve fibers in the stroma layer was obviously thicker than that of the hyphae.Conclusions The diagnosis rate of confocal laser scanning microscope combined with slit-lamp microscope for filamentous fungi-infectious FK is higher than that of fungal culture.The combination procedure of confocal laser scanning microscope and slit lamp microscope examination provides a rapid evaluation for fungi strains and therapeutic efficacy in the FK patients with negative results by fungal culture.