[Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages].

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

[Research advances on size selection and vault prediction of posterior chamber phakic intraocular lens].

Posterior chamber phakic intraocular lens (pIOL) implantation has been widely adopted for the correction of refractive errors. Among pIOLs, the Implantable Collamer Lens is the most common choice. The selection of the appropriate pIOL size and achieving the desired postoperative vault to minimize complications has consistently been a focal point in academic research. With the advancement of ophthalmic biometric measurement technology and the application of artificial intelligence in the field of medicine, numerous new technologies and methods for pIOL size selection and vault prediction have emerged in recent years. This paper provides a comprehensive review on the topic of how to choose the pIOL size and predict the vault.

[Advances of tight junction damage in the corneal epithelial barrier in the pathogenesis of corneal diseases].

The cornea is a transparent tissue with significant refractive and barrier functions. Corneal epithelium constitutes the first line of defense against foreign pathogens. Corneal epithelial cells interact to form a functionally selective permeability barrier. Dysfunction of this barrier leads to corneal impairment followed by a series of ocular surface diseases and even blindness. Tight junctions (TJ), located at the top of the intercellular space of corneal epithelial superficial cells, play a critical role in establishing and maintaining the barrier function. Previous studies have shown that destruction of the TJ acts as a crucial step of the occurrence and progression of multiple ocular surface diseases. Understanding the fundamental features and functions of the TJ, noticing the risk factors of TJ disruption, and clarifying the key role of TJ in the pathogenesis of various ocular surface diseases will help to better understand and treat ocular surface diseases.

[Research advances of morphological changes of the choroid in high myopia].

Choroidal thinning is an important feature of high myopia and has a negative correlation with the degree of myopia. However, due to the limitations of choroidal imaging, specific changes in choroidal thickness and vasculature are unclear. In recent years, the development of optical coherence tomography technology and optical coherence tomography angiography technology has made it possible to solve the problem. Emergence of biomarkers that objectively quantify choroidal thickness and vascular changes will help us understand the pathogenesis of high myopia and provide new ideas for the prognosis and treatment of myopia. In this review, in order to provide reference for clinical work, we summarize recent advances in the application of the two technologies in observing morphological changes of the choroid in high myopia and discuss the problems and prospects when they are combined with artificial intelligence for choroidal imaging. (Chin J Ophthalmol, 2021, 57: 459-464).

Analysis on the relationship and mechanism of high blood pressure and vascular aging on the condition that the gender and age matches.

OBJECTIVE: The relationship between hypertension and the mechanism of the expression of T-lymphocyte Kv1.3 channels in vascular aging has been analyzed in this study based on the gender and age matches' principle. PATIENTS AND METHODS: Thirty patients have been consecutively chosen with vascular aging caused by hypertension (group A), while 30 cases of high blood pressure not merged with vascular aging (group B) were chosen, and 30 cases of healthy volunteers (group C), conforming to gender and age 1:1 and the closest matching principle, were studied. The aim of this study was to separate the peripheral blood mononuclear cells and give intervention of 0.2 nmol/L ANGII to CD4 + T-lymphocytes, and store them in the incubator 48 h. The difference of Kv1.3 channel current of CD4 + T-lymphocyte, mRNA, angiotensin receptor (AT1R) protein mRNA, and IFN-γ density has also been compared. RESULTS: The membrane capacitance, peak current, and current density of group A, are higher than those of the other two groups, and the differences have statistical significance (p<0.05). After adding ANGII intervention to group A, the expression levels of T-lymphocyte Kv1.3 potassium channels mRNA, AT1R mRNA, and IFN-γ are significantly increased, so that the difference has statistical significance p<0.05, while the other two groups have no significant change (p>0.05). The levels of Kv1.3 potassium channels, AT1R mRNA, and IFN-γ of group A before and after the intervention are significantly higher than those of the other two groups, and the differences are statistically significant (p<0.05). CONCLUSIONS: Vascular aging caused by hypertension may be linked to the increase of Kv1.3 potassium channel activity of T-lymphocyte, while ANGII can improve the high expression of Kv1.3 potassium channel and AT1R, to stimulate lymph cells to secrete IFN-γ.

[Intracranial mixed germ cell tumor].

Objective: To study intracranial mixed germ cell tumor diagnosis and reasonable treatment strategy. Methods: Clinical data of 17 patients with intracranial mixed germ cell tumor in Tsinghua university Yuquan hospital from October 2012 to October 2016 were retrospective analysed, including the characteristics of the general, the serum tumor markers of AFP, ß-HCG, and CEA, imaging findings, pathological results, treatment methods and prognosis. Results: There were 10 cases of male, 7 cases of female. The average age was (11.1±5.2) years old. Nine cases were gross total resection of lesions and 8 cases were subtotal resection of lesions. Eight cases (47.1%) were without recurrence and had more than four courses of chemotherapy after surgery, of which, 7 cases belonged to the gross total resection, and 1 case belonged to the subtotal resection. Nine (52.9%) patients relapsed, including 2 cases of the gross total resection and 7 cases of the subtotal resection. Among them, 4 cases were given second operations and 6 cases obtained satisfactory therapeutic effect by chemotherapy combined radiotherapy. There were 12 of 17 patients with pathological types contain teratoma (including mature, immature or malignant teratoma) ingredients, accounting for 70.6%. The average follow-up time was (17.5±12.1) months, 4 cases (23.5%) patients died. Conclusion: The diagnosis of intracranial mixed germ cell tumors needs comprehensive consideration of tumor markers in serum or cerebrospinal fluid, chemotherapy and radiotherapy before operation and pathological results. The gross total resection helps to reduce the chances of tumor recurrence. Rational chemotherapy and radiotherapy is helpful to prognosis.

[Allogeneic cultured limbal epithelial transplantation: a clinical observation of its treatment effects on large conjunctival lesions].

Objective: To introduce the surgical methods and investigate the treatment effects of conjunctival lesion resection combined with transplantation of allogeneic limbal epithelia cultured in vitro for treatment of varied large conjunctival lesions. Methods: A retrospective analysis of case data of the patients receiving transplantation of allogeneic limbal epithelia cultured in vitro for large conjunctival lesions at Qingdao Eye Hospital from January 2013 to December 2015 was conducted. Fresh donor corneal limbal epithelial tissues were obtained for cellular digestion and isolation. The cells were cultured on de-epithelized amniotic membrane to form a stratified cell sheet with 3 to 5 layers of cells for reservation. Conjunctival lesions were removed, and corneal limbal epithelial cell sheets corresponding to the size of the conjunctival defects were covered on the scleral flaps, before the conjunctivae were para sutured with corneal limbal epithelial cell sheets. The stitches were removed 7 days after surgery. The treatment effects were evaluated. Results: There were 11 cases (12 eyes) in this study, including 6 cases (6 eyes) of recurrent pterygium combined with symblepharon, 3 cases (3 eyes) of conjunctival compound nevus, 1 case (1 eye) of conjunctival primary acquired melanosis, and 1 case (2 eyes) of dermoid lipoma. The patients were 6 to 69 years old, with an average age of (46±23) years old. There were 5 male patients and 6 female patients. The follow-up time was 6 to 39 months, with an average time of (24.8±12.4) months. The conjunctival lesions in all patients were more than 2 quadrants. No patients had intraoperative and postoperative complications. No obvious irritation symptoms were observed after surgery. There were a few small pieces of epithelial defects on the limbal epithelial cell sheets at the end of the operation due to operative injury. With postoperative cellular proliferation and repair, the epithelium gradually healed and tended to become firm, and the boundaries with original conjunctival epithelium gradually disappeared. The healing time of the epithelium after surgery was 3 to 7 days, with an average time of (4.5±1.2) days. No immunological rejection occurred after surgery. No recurrence of original diseases was observed among all the patients at the last follow-up. Conclusions: Transplantation of allogeneic cultured limbal epithelial cells, which was carried out for the treatment of large conjunctival lesions, witnessed rapid epithelization at the areas of lesion resection. It could reduce the risk of recurrence of original diseases and effectively avoid the occurrence of postoperative symblepharon. The postoperative inflammatory reaction was also minor. (Chin J Ophthalmol, 2017, 53:172-176).

[Analysis of clinical features and related factor of syncope and head-up tilt test results in children].

OBJECTIVE: To analyze the relationship between clinical features of vasovagal syncope (VVS) and results of head-up tilt test (HUTT). METHOD: The study enrolled 146 children who were suspected with VVS from January 2014 to January 2015 in West China Second University Hospital, while other organic diseases were excluded, including 54 males and 92 females, aged from 5-17 years, whose average age was from (11.5±3.2) years old. Specified staff was assigned to inquire clinical histories, perform physical exam and HUTT composed of baseline HUTT (BHUTT) and sublingual nitroglycerin HUTT (SNHUTT). According to HUTT results, the patients were divided into two groups: HUTT positive group confirmed with VVS and HUTT negative group. The distributions of hemodynamic types and most common clinical manifestations were analyzed. The factors which were statistically significant in single factor analysis were selected to perform the Logistic regression for screening independent risk factors for HUTT positivity. RESULT: Of the 146 patients suspected with VVS, 86 cases were positive for HUTT, while 60 cases were negative. (1)HUTT hemodynamic types: In the total of 86 positive cases, 22 cases were positive at baseline for BHUTT (11 mixed response, 8 vasodepressor and 3 cardiodepressor), while 64 were positive in SNHUTT (34 mixed response, 21 vasodepressor and 9 cardiodepressor). (2)CLINICAL FEATURES: The most common manifestations in HUTT-positive group were, in order, headache or dizziness (66.3%), syncope (65.1%), chest tightness or fatigue (41.9%), nausea, vomiting or abdominal pain (25.6%), palpitation (10.5%). (3)The single factor analysis demonstrated that female (χ(2)=7.402, P=0.007), age>12 years (χ(2)=14.649, P<0.001), with family history (χ(2)=11.431, P=0.001) or flare-up of syncope (χ(2)=11.496, P=0.001) and headache or dizziness (χ(2)=5.589, P=0.018) were risk factors for positive HUTT. (4)Logistic regression analysis indicated that female (OR=2.396, P=0.006), age>12 years (OR=3.765, P=0.020), with family history (OR=1.998, P=0.023) or flare-up of syncope(OR=2.298, P=0.022) were independent risk factors for positive HUTT. CONCLUSION: Female, age>12 years, with family history or flare-up of syncope are related factors for positive HUTT.

Effect of atorvastatin on plasma NT-proBNP and inflammatory cytokine expression in patients with heart failure.

The aim of this study was to explore the effect of atorvastatin intervention on plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and inflammatory cytokine levels in patients with heart failure (HF). One hundred and twenty-three HF patients were selected from our hospital and randomly divided into control (N = 61) and observation (N = 62) groups; the former received conventional treatment, while the latter were given conventional treatment combined with atorvastatin. Plasma NT-proBNP, inflammatory cytokines [high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10] and cardiac function [left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), end-diastolic maximum flow rate ratio (E/A)] were compared among groups. The effective rate of treating HF significantly increased after atorvastatin treatment. The plasma NT-proBNP, IL-6, IL-10, hs-CRP, and LVEDD levels significantly decreased (P < 0.05), while the LVEF and E/A levels significantly increased (P < 0.05) in the observation group compared to the control group and before intervention. The NT-proBNP and cytokine levels significantly differed among patients with different classes of heart function (P < 0.05); the NT-proBNP and cytokine levels increased with the severity of heart function. Pearson's correlation analysis revealed a negative correlation between the NT-proBNP and inflammatory cytokine levels and LVEF and E/A values, and a positive correlation between these factors and LVEDD (P < 0.05). In conclusion, atorvastatin significantly improves cardiac function; the mechanism atorvastatin action was related to the decrease in plasma NT-proBNP and inflammatory cytokine levels.

Association of interleukin gene polymorphisms with the risk of coronary artery disease.

We conducted a case-control study to investigate the genetic variants Interleukin-1ß(IL-1ß) +3953 C/T (rs1143634), IL-6 -174G/C (rs1800795), IL-8 -251T/A (rs4073), and IL-10 -1082A/G (rs1800896) and -819C/T (rs1800871) in the development of coronary artery disease (CAD). A total of 410 individuals with CAD were enrolled between January 2012 and December 2014. Genotyping of the five gene polymorphisms was performed using the polymerase chain reaction combined with restriction fragment length polymorphism methodology. By multivariate logistic regression analysis, we found that the frequencies of the CC genotype and the C allele of IL-6 -174G/C were significantly correlated with a higher risk of CAD; the adjusted ORs (95%CIs) were 2.37 (1.37-4.14) and 1.49 (1.19-1.86), respectively. In addition, the AG and GG genotypes and the G allele of IL-10 -1082A/G were also significantly associated with a higher risk of CAD, and the ORs (95%CIs) were 1.42 (1.04-1.95), 2.16 (1.42-3.30), and 1.56 (1.27-1.93), respectively. However, IL-1ß+3953 C/T, IL-8 -251T/A, and IL-10 -819C/T did not significantly correlate with CAD risk. Our study suggests that the IL-6 -174G/C (rs1800795) and IL-10 -1082A/G (rs1800896) polymorphisms might be involved in the pathogenesis of CAD, and likely contribute to the genetic susceptibility for CAD.

Therapeutic effects of dengue 2 virus capsid protein and staphylococcal nuclease fusion protein on dengue-infected cell cultures.

Dengue infection poses a serious public health problem in most tropical and subtropical areas. No effective antiviral drugs or vaccines are currently available against dengue infection. To explore the feasibility of using capsid-targeted viral inactivation (CTVI) as an antiviral strategy against dengue infection, we constructed a plasmid expressing a fusion protein consisting of staphylococcal nuclease (SN) fused to dengue 2 virus capsid protein (D2C), and investigated its effects on the production of infectious virions when introduced into BHK cells infected with dengue virus. The results indicated that D2C-SN can be expressed and tolerated in this mammalian cell culture. The enzymatically active SN moiety was incorporated into nascent virions during the process of viral assembly. By comparing the effects of incorporated SN and SN*, an enzymatically inactive missense mutant form of wild-type SN, on the infectivity of progeny virions, we clearly demonstrated that nucleolytic activity was the major antiviral mechanism. Expression of D2C-SN fusion protein as a therapeutic agent resulted in a reduction in infectious titers of 12- to 60-fold. Therefore, dengue virus may be particularly vulnerable to a CTVI therapeutic approach.

An atlas of renography with Tc-99m sestamibi: comparison with Tc-99m DTPA.

Tc-99m sestamibil demonstrates considerable renal uptake followed by net urinary clearance similar to that of creatinine. The authors have previously shown that renograms could be obtained in cardiac patients by imaging during the rest injection of the perfusion agent. The present study shows correlating Tc-99m sestamibi and Tc-99m DTPA studies in hypertensive patients with a spectrum of findings, including aortic aneurysms, asymmetry due to renovascular disease, cysts, bilateral renal dysfunction, and horseshoe kidney. Tc-99m sestamibi images have persisting background activity in the liver and spleen, but show renal structure and function in adequate detail. Quantitative analysis confirms that Tc-99m sestamibi has higher renal uptake, but less excretion than Tc-99m DTPA. Review of these correlating studies suggests straightforward transfer of diagnostic expertise with standard renography to this new application.