Independent association between prostate-specific antigen nadir and PSA progression-free survival in first-line abiraterone acetate treatment in castration-resistant prostate cancer patients: a pilot study.

Background: There is limited evidence regarding the correlation between prostate-specific antigen (PSA) kinetics and clinical outcomes. Therefore, after regulating other covariates, we studied patients with castration-resistant prostate cancer who received abiraterone acetate as the first-line treatment. In this study, we investigated whether time to PSA nadir was independently associated with PSA progression-free survival (PFS). Methods: As a retrospective cohort study, this study contained a total of 77 castration-resistant prostate cancer patients who received abiraterone acetate from October 2015 to April 2021 in a Chinese hospital. The dependent variable was PSA-PFS. The objective independent variable was time to PSA nadir (TTPN). Covariates involved in this study included age, duration of androgen deprivation therapy (ADT), PSA level at baseline, time of 50% PSA decline, time of PSA decline to nadir, Gleason score, bone metastasis, previous treatment, PSA decline <50% in 3 months, PSA to nadir in 3 months, PSA decline <90%, PSA decline <0.2 ng/mL, and PSA flare. Results: For the 77 subjects, their mean age was 72.70 ± 8.08 years. Fully calibrated linear regression findings indicated that PSA decline and kinetics were positively associated with PFS (months) after adjusting confounders (ß = 0.77, 95% CI: 0.11-1.44). A non-linear relationship was not detected between PSA decline or PSA kinetics and progression-free survival. Conclusion: According to the data of this study, there was a correlation between early PSA changes and patients treated with abiraterone acetate.

Effect of sodium fluorescein strip application on cornea parameters commonly used in laser-assisted in-situ keratomileusis.

To assess the effect of sodium fluorescein (NaF) strip on corneal parameters commonly used in Laser-assisted in-situ keratomileusis (LASIK). Eighty-six subjects (172 eyes) scheduled for LASIK were recruited between January and March 2022. The study and statistical analysis test were conducted in April 2022. Topographic measurements of corneal parameters, including central corneal thickness (CCT), anterior keratometric (K) readings (K1, flat keratometry; K2, steep keratometry), horizontal corneal diameter (white to white, WTW), and corneal asphericity (Q value), were obtained using a Scheimpflug device (Pentacam) before and 10 min after NaF strip treatmentThe Pentacam recorded a small significant increase in CCT (mean 538.88 ± 28.78 µm to 547.90 ± 29.94 µm; p < .001), with no differences in K1 and K2 (mean 42.24 ± 1.35D to 42.24 ± 1.35D, and mean 43.34 ± 1.50D to 43.32 ± 1.51D; P > .05, for all) as well as WTW(mean 11.58 ± 0.32 mm to 11.58 ± 0.32 mm, P > .05) before and after NaF strip intervention. Furthermore, there was no significant difference was observed in Q value (mean - 0.30 ± 0.13 to - 0.30 ± 0.14, P > .05). These results indicate that clinicians should avoid NaF strip application before obtaining precise topographic measurements of cornea parameters using the Pentacam.

Effects of Uremic Clearance Granules on p38 MAPK/NF-κB Signaling Pathway, Microbial and Metabolic Profiles in End-Stage Renal Disease Rats Receiving Peritoneal Dialysis.

Background: End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). In the clinic, Uremic Clearance Granules (UCG) are mainly used in the treatment of early CKD and stabilized renal function. However, the benefits and mechanisms of UCG on ESRD remain unclear. Methods: Rats were randomly divided into four groups: sham group, model group, peritoneal dialysis (PD) group and UCG group. Except for the sham-operated group, ESRD was induced by 5/6 nephrectomy in the other three groups. The PD group and UCG group were then subjected to PD. In addition, the UCG group was given UCG by gavage when PD. Changes in body weight and final kidney weight of rats in each group were monitored. HE and Masson staining were performed to confirm the extent of renal fibrosis. Biochemical kits were used to detect blood urea nitrogen (BUN), serum and urine creatinine (Scr, Cre), and urine protein (UPr) levels. ELISA was used to detect the rats' inflammatory responses. qRT-PCR, WB, and IHC were probed to determine the expression levels of NF-κB and MAPK. 16S rDNA sequencing was performed to analyze the composition of gut microbiota in rats. A liquid chromatograph-mass spectrometer was performed to reveal serum metabolomics changes. Results: UCG increased renal volume and body weight, improved renal fibrosis. It enhanced renal function and decreased the levels of BUN, Scr, Upr, Cre, inflammatory responses, as well as NF-κB and MAPK expressions in renal and colon tissues of ESRD rats. The relative abundances of Bacteroidetes and Firmicutes changed in ESRD rats in response to UCG. Serum metabolomics was utilized to identify 70 differentiated metabolites, which were associated with D-glutamine and D-glutamate metabolism, and Phenylalanine metabolism. Conclusion: Our study confirmed that UCG alleviated ESRD by regulating p38 MAPK/NF-κB signaling pathway, microbial and metabolic profiles.

Mixed Vaginitis in the Third Trimester of Pregnancy Is Associated With Adverse Pregnancy Outcomes: A Cross-Sectional Study.

Mixed vaginitis is a complex vaginal dysbiosis that differs from single vaginitis. Vaginitis in the third trimester may lead to adverse maternal and neonatal outcomes. The clinical characteristics, microbiological characteristics, and adverse pregnancy outcomes of mixed vaginitis in late pregnancy are worth studying. Therefore, this study investigated the clinical and microbiological characteristics of vaginitis and adverse pregnancy outcomes of patients with mixed vaginitis. We studied 1,674 women in late pregnancy who attended the Tianjin Medical University General Hospital from November, 2019 to October, 2021. We administered standardized questionnaires, performed vaginal examination and sampling plus microscope examinations, and assessed follow-up pregnancy outcomes. We cultured the vaginal discharge of the patients with mixed vaginitis to isolate pathogens and performed antimicrobial susceptibility tests of the isolated pathogens. For the patients with peripartum infection, we collected a sample to isolate pathogens. Among the 1,674 women, 66 (3.9%) had mixed vaginitis. The independent risk factor for mixed vaginitis in late pregnancy was a history of vaginitis during early and middle pregnancy (OR = 5.637, 95% CI: 3.314-9.580). The signs of vaginal erythema (63.6% vs. 42.0%), yellow discharge (81.8% vs. 59.6%), and malodor (31.8% vs. 18.8%) (P <0.05) were significantly higher in patients with mixed vaginitis than in patients with single vaginitis. Bacterial isolates of the vaginal secretions of patients with mixed bacterial vaginitis were mainly the pathogens of aerobic vaginitis and bacterial vaginosis, such as Gardnerella vaginalis, Streptococcus anginosus, and Staphylococcus epidermidis. Pathogen isolation of the vaginal secretions of patients with mixed fungus and bacteria vaginitis mainly included Candida albicans, followed by S. anginosus, Enterococcus faecalis, Staphylococcus hemolyticus, Staphylococcus aureus, Streptococcus agalactiae and Staphylococcus simulans. Women with mixed vaginitis had an increased incidence and risk of peripartum infections (6.1% vs. 1.4%, P <0.05; OR = 3.985, 95% CI:1.214-13.079). Escherichia coli is the main pathogen that causes peripartum infection. Mixed vaginitis in late pregnancy is characterized by a severe and complex phenotype, complex vaginal dysbiosis, and a long course of vaginal dysbiosis. This can lead to an increased incidence and risk of peripartum infection. Therefore, more attention should be paid to patients with mixed vaginitis in the third trimester of pregnancy.

Anesthetic management of precise radiotherapy under apnea-like condition.

OBJECTIVE: To study the safety and feasibility of implementation of precise radiotherapy with inducement of an apnea-like condition. METHODS: Two patients with lung tumors underwent precise radiotherapy under an apnea-like condition. The apnea-like condition was induced 11 times between the two patients for tumor localization and treatment. The changes in the blood oxygen saturation, blood pressure, heart rate, and end-tidal carbon dioxide during the apnea-like periods were observed, and the incidence of adverse reactions was recorded. RESULTS: The average apnea-like time was 6.2 minutes (range, 3-9 minutes), and the average radiotherapy time was 4.6 minutes (range, 1-7 minutes). The lowest blood oxygen saturation level was 97%, with a change of <1%. The heart rate and average arterial blood pressure increased during the apnea-like periods. Contact sores appeared on the patients' posterior pharyngeal wall after the first apnea-like period; no other adverse events occurred. CONCLUSION: Precise radiotherapy under an apnea-like condition is safe and feasible for patients with lung tumors.

Binocular integration and stereopsis in children with television torticollis.

BACKGROUND: To observe the characteristics of binocular integration and stereopsis in children with television torticollis. METHODS: A retrospective study was carried out, where data were collected from 25 children with television torticollis as the disease group after refractive error correction and 25 normal children as the control group. A virtual reality system was used to assess and analyze the characteristics of binocular integration by a contrast balance test and binocular stereopsis. RESULTS: The 25 children in the disease group included 17 males and 8 females with an average age of 7.5 ± 1.9 years old and an average binocular spherical equivalent of - 0.35 ± 1.46D. The 25 children in the control group were also 17 males and 8 females with an average age of 7.3 ± 2.2 years old and the average binocular spherical equivalent of - 0.48 ± 0.93D. No significant differences were found in the horizontal bar contrast balance test between the 2 groups at near and far distances. Near-distance vertical bar contrast balance test was normal in 23 subjects and suppressed in 2 subjects in the control group, while it was normal in 13 subjects and suppressed in 12 subjects in the disease group, which showed a statistically significant difference (P = 0.002). Far distance vertical bar contrast balance test was normal in 24 subjects and suppressed in 1 subject in the control group, normal in 7 subjects and suppressed in 18 subjects in the disease group, showing a statistically significant difference (P = 0.000). All subjects in the 2 groups showed 100〞 as near distance stereoacuity. At far distance, the mean stereoacuity was 176.00〞 ± 92.56〞 in the control group, and 352.00〞 ± 270.99〞 in the disease group, with a statistically significant difference (P = 0.011). CONCLUSION: By using virtual reality technology, defects in binocular visual function were found in children whose television torticollis persisted after regular refractive error correction. Television torticollis may be associated with the deficit of binocular integration for vertical bars and far distance stereopsis.

Interplay between orphan nuclear receptors and androgen receptor-dependent or-independent growth signalings in prostate cancer.

It is well-established that both the initial and advanced growth of prostate cancer depends critically on androgens and thus on the activated androgen receptor (AR) -mediated signaling pathway. The unique hormone-dependent feature of prostate cancer forms the biological basis of hormone or androgen-deprivation therapy (ADT) that aims to suppress the AR signaling by androgen depletion or AR antagonists. ADT still remains the mainstay treatment option for locally advanced or metastatic prostate cancer. However, most patients upon ADT will inevitably develop therapy-resistance and progress to relapse in the form of castration-resistant disease (castration-resistant prostate cancer or CRPC) or even a more aggressive androgen-independent subtype (therapy-related neuroendocrine prostate cancer or NEPC). Recent advances show that besides AR, some ligand-independent members of nuclear receptor superfamily-designated as orphan nuclear receptors (ONRs), as their endogenous physiological ligands are either absent or not yet identified to date, also play significant roles in the growth regulation of prostate cancer via multiple AR-dependent or -independent (AR-bypass) pathways or mechanisms. In this review, we summarize the recent progress in the newly elucidated roles of ONRs in prostate cancer, with a focus on their interplay in the AR-dependent pathways (intratumoral androgen biosynthesis and suppression of AR signaling) and AR-independent pathways or cellular processes (hypoxia, oncogene- or tumor suppressor-induced senescence, apoptosis and regulation of prostate cancer stem cells). These ONRs with their newly characterized roles not only can serve as novel biomarkers but also as potential therapeutic targets for management of advanced prostate cancer.

Comparisons of Ocular Anatomic Differences of Lens-Subluxated Eye with or without Acute Angle Closure: A Retrospective Study.

PURPOSE: To compare ocular anatomy differences of lens subluxation between eyes with or without acute angle closure (AAC). METHODS: This is a retrospective and case-control study. Sixty cases with mild lens subluxation were recruited. Among them, 30 eyes with acute angle closure were assigned to the AAC group and 30 eyes without AAC were assigned to the non-AAC group. The anterior segment was quantitatively evaluated by ultrasound biomicroscopy (UBM). The axial length (AL) was measured with IOL Master. All patients underwent lens extraction surgery and were followed up for six months. RESULTS: The history of blunt trauma accounted for 22 (73.3%) cases in the AAC group and 21 (70%) cases in the non-AAC group. Fifteen (50%) patients in the AAC group had iridotomy history, and high intraocular pressure recurred. The UBM analysis showed that the average central chamber depth of the affected eyes in the AAC group was 1.82 mm, which was significantly shallower than that in the fellow eyes (2.58 mm, P < 0.05) or both eyes in the non-AAC group.Both eyes in the AAC group presented a shorter AL and shallower anterior chamber than the eyes in the non-AAC group. CONCLUSIONS: An asymmetrical anterior chamber between bilateral eyes is an important feature in lens subluxation-induced AAC. The crowded anterior chamber and shorter AL might be the anatomic basis for the eye with lens subluxation-induced AAC.

Microvascular changes in macula and optic nerve head after femtosecond laser-assisted LASIK: an optical coherence tomography angiography study.

BACKGROUND: To measure the microcirculation change of macula and optic nerve head before and after femtosecond laser assisted laser in situ keratomileusis. METHODS: In total 45 eyes from 45 subjects, who underwent FS-LASIK during June 2017 to December 2017 in Guangdong Provincial People's Hospital, were recruited in this study. Vessel density in macula and optic nerve head were measured by optical coherence tomography angiography before and after transient elevation in intraocular pressure caused by application of suction ring during surgery. RESULTS: Vessel density (VD) at superficial (SCP) plexus of macular region did not differ after surgery (F(3,132) = 1.41, P = 0.24), while the deep (DCP) plexus of macular region significantly decreased 1 day after surgery (P = 0.001) but returned to its baseline value 1 month postoperatively (P = 0.1). Vessel density of optic nerve head region had no significant changes after surgery (F(2.51,95.18) = 0.6, P = 0.59). CONCLUSIONS: A short-term temporary decrease of vessel density at deep layer of macular region was observed in eyes undergoing FS-LASIK. However, the retinal capillary density went back to preoperative level 1 month after surgery. Therefore, transient IOP spike during FS-LASIK did not cause long-term decline of retinal microcirculation.

Metabolic engineering of Saccharomyces cerevisiae using the CRISPR/Cas9 system to minimize ethyl carbamate accumulation during Chinese rice wine fermentation.

Ethyl carbamate (EC) is a potential carcinogen to humans that is mainly produced through the spontaneous reaction between urea and ethanol during Chinese rice wine brewing. We metabolically engineered a strain by over-expressing the DUR3 gene in a previously modified strain using an improved CRISPR/Cas9 system to further decrease the EC level. Homologous recombination of the DUR3 over-expression cassette was performed at the HO locus by individual transformation of the constructed plasmid CRISPR-DUR3-gBlock-HO, generating the engineered strain N85DUR1,2/DUR3-c. Consequently, the DUR3 expression level was significantly enhanced in the modified strain, resulting in increased utilization of urea. The brewing test showed that N85DUR1,2/DUR3-c reduced urea and EC concentrations by 92.0% and 58.5%, respectively, compared with those of the original N85 strain. Moreover, the engineered strain showed good genetic stability in reducing urea content during the repeated brewing experiments. Importantly, the genetic manipulation had a negligible effect on the growth and fermentation characteristics of the yeast strain. Therefore, the constructed strain is potentially suitable for application to reduce urea and EC contents during production of Chinese rice wine. KEY POINTS: • An efficient CRISPR vector was constructed and applied for DUR3 over-expression. • Multi-modification of urea cycle had synergistic effect on reducing EC level. • Fermentation performance of engineered strain was similar with the parental strain. • No residual heterologous genes were left in the genome after genetic manipulation. • An efficient CRISPR vector was constructed and applied for DUR3 over-expression. • Multi-modification of urea cycle had synergistic effect on reducing EC level. • Fermentation performance of engineered strain was similar with the parental strain. • No residual heterologous genes were left in the genome after genetic manipulation.

Virtual Reality Assessment Reveals Myopic Regression After ICL Implantation in High Myopia.

PURPOSE: To investigate the correlative factors of vision regression after Implantable Collamer Lens (ICL) surgery from the perspective of binocular vision and to develop a predictive model for the refractive change over the long term. METHODS: This was a prospective study of 30 subjects (60 implants), who underwent ICL surgery at Guangdong General Hospital. Corrected distance visual acuity, uncorrected distance visual acuity, spherical equivalent (SE), axial length and binocular examination using virtual reality were analyzed before, 1 month and 1 year after the surgery. RESULTS: Mean SE was (-12.01 ± 0.86) D preoperatively, (-0.44 ± 0.13)D 1 month postoperatively and (-0.97 ± 0.15)D 1 year postoperatively. The average regression 1 year postoperatively (-0.53 ± 0.25D of SE) was significant (P = 0.01). Mean axial length at the base line and 1 year after the surgery was (28.35 ± 0.39) mm and (28.91 ± 0.57) mm. The regression was correlated with the binocular equilibrium difference (r = 0.553, P = 0.002), and the degree of perceptual eye position shift, especially the horizontal shift (r = -0.620, P = 0.000). The important variables relevant to myopic regression were preoperative horizontal perceptual eye position shift (B = -0.007, P = 0.001) and binocular equilibrium difference (B = 0.146, P = 0.012). CONCLUSION: Perceptual eye position deviation and the binocular equilibrium difference could cause binocular gazing instability, and the unstable retinal image created a 'micro retinal-defocus phenomena', leading to an elongation of the axial length and resulting in myopic regression after ICL surgery.

Complete chloroplast genomes of two Siraitia Merrill species: Comparative analysis, positive selection and novel molecular marker development.

Siraitia grosvenorii fruit, known as Luo-Han-Guo, has been used as a traditional Chinese medicine for many years, and mogrosides are its primary active ingredients. Unfortunately, Siraitia siamensis, its wild relative, might be misused due to its indistinguishable appearance, not only threatening the reliability of the medication but also partly exacerbating wild resource scarcity. Therefore, high-resolution genetic markers must be developed to discriminate between these species. Here, the complete chloroplast genomes of S. grosvenorii and S. siamensis were assembled and analyzed for the first time; they were 158,757 and 159,190 bp in length, respectively, and possessed conserved quadripartite circular structures. Both contained 134 annotated genes, including 8 rRNA, 37 tRNA and 89 protein-coding genes. Twenty divergences (Pi > 0.03) were found in the intergenic regions. Nine protein-coding genes, accD, atpA, atpE, atpF, clpP, ndhF, psbH, rbcL, and rpoC2, underwent selection within Cucurbitaceae. Phylogenetic relationship analysis indicated that these two species originated from the same ancestor. Finally, four pairs of molecular markers were developed to distinguish the two species. The results of this study will be beneficial for taxonomic research, identification and conservation of Siraitia Merrill wild resources in the future.

BRMS1 participates in regulating cell sensitivity to DNA interstrand crosslink damage by interacting with FANCI.

Breast cancer metastasis suppressor 1 (BRMS1) is a tumor metastasis suppressor implicated in multiple steps during the metastatic cascade. Many proteins interacting with BRMS1 have been identified to unravel the intracellular signaling mechanisms. In the present study, we report that FANCI is a novel interacting protein of BRMS1 as determined by co­immunoprecipitation assay. The linker region between two coiled­coil motifs of BRMS1 is required for BRMS1­FANCI interaction. FANCI is an essential protein in the Fanconi anemia (FA) pathway responsible for the repair of DNA interstrand crosslinks (ICLs). We demonstrated that knockdown or knockout of BRMS1 significantly diminished the monoubiquitination of FANCI and FANCD2 in response to DNA ICL damage. BRMS1­deficient cells exhibited suppressed FANCD2 foci formation and hypersensitivity to ICLs. Moreover, rescue assays by utilizing different BRMS1 constructs suggested that BRMS1­FANCI interaction is necessary for the regulatory role of BRMS1 in the FA pathway. Overall, our findings characterize BRMS1 as a novel regulatory protein functioning in the DNA repair pathway via protein interaction.

Intermittent Exotropia Treatment with Dichoptic Visual Training Using a Unique Virtual Reality Platform.

We evaluated the effect of dichoptic visual training based on a unique virtual reality (VR) platform mounted display in patients with intermittent exotropia (IXT). A total of 25 IXT patients (8 men, 17 women) with a mean age of 12.3 years (range, 5-39 year) were recruited. The Hirschberg test, prism and alternate cover testing (with accommodative targets for fixation at 33 cm in all patients), perceptual eye position (PEP), and stereopsis were evaluated after 1, 3, and 6 months of dichoptic visual neuroplasticity training with a computer-controlled perceptual examination evaluation system. Data collected before and after training were evaluated using SPSS software. After 6 months of perceptual training, a new order stereopsis was established, and eye positions were improved in all 25 patients. After training for 1 and 6 months, the horizontal PEP pixels were much lower than those pretraining, respectively (Δ1-0 = -0.53, p = 0.028; Δ6-0 = -0.80, p = 0.018). There was no statistically significant difference between pretraining and 3 months after training in horizontal PEP (Δ3-0 = -0.29, p = 0.370). There was no significant difference between pretraining and post-training in vertical PEP (p > 0.05). There were significant differences between pretraining and post-training in the cornea's optical reflection and prism diopters (p < 0.01). Dichoptic visual neuroplasticity training based on a VR platform is an effective nonsurgical treatment in patients with IXT. With the VR treatment, the degree of strabismus and stereopsis was improved in IXT patients. Perceptual training with VR can remove obstacles in the visual processing channel and repair defects in visual function. The clinical manifestations of improvement were the decrease in the degree of strabismus and the re-establishment of stereopsis.

Knockdown of ZNF233 suppresses hepatocellular carcinoma cell proliferation and tumorigenesis.

Zinc finger proteins (ZNFs) are one of the most abundant proteins in eukaryotic genomes with extraordinarily diverse functions. ZNF233 is located on 19q13.31 and encodes a 670-amino acid protein belonging to the Krüppel C2H2-type ZNF family. However, little is known about the role of ZNF233 in cancer progression. In this study, we reported for the first time that ZNF233 mRNA was remarkably up-regulated in hepatocellular carcinoma (HCC) tissues in comparison with corresponding non-tumorous normal liver tissues. ZNF233 expression level was correlated with tumor grade, tumor stage and prognosis of HCC patients. We further investigated the effect of ZNF233 on HCC cell growth. It is found that overexpression of ZNF233 in SMMC-7721 could promote G1/S transition and thus accelerate cell growth ratio. Consistently, knockdown of ZNF233 in QGY-7701 cells successfully suppressed cell proliferation in vitro and in vivo. Further immunohistochemical staining revealed a reduced Ki-67-positive cell percentage in xenografted tumor derived from ZNF233-knocking down cells. Taken together, these results demonstrate a positive role of ZNF233 in regulating HCC cell growth. ZNF233 might be developed as a novel biomarker and a potential therapeutic target for HCC.

Scinderin is a novel transcriptional target of BRMS1 involved in regulation of hepatocellular carcinoma cell apoptosis.

Tumor metastasis suppressor factor BRMS1 can regulate the metastasis of breast cancer and other tumors. Here we report scinderin (SCIN) as a novel transcriptional target of BRMS1. SCIN protein belongs to the cytoskeletal gelsolin protein superfamily and its involvement in tumorigenesis remains largely illusive. An inverse correlation between the expression levels of BRMS1 and SCIN was observed in hepatocellular carcinoma (HCC) cells and tissues. On the molecular level, BRMS1 binds to SCIN promoter and exerts a suppressive role in regulating SCIN transcription. FACS analysis and caspase 9 immunoblot reveal that knockdown of SCIN expression can sensitize HCC cells to chemotherapeutic drugs, leading to suppression of tumor growth in vivo. Consistently, overexpression of SCIN protects cells from apoptotic death, contributing to increased xenografted HCC cell growth. In summary, our study reveals SCIN as a functional apoptosis regulator as well as a novel target of BRMS1 during HCC tumorigenesis. Inhibition of SCIN might bring a potential cancer therapy approach.

[Effects of Electroacupuncture and Moxibustion Pretreatment on Expressions of HSP 27, HSP 70, HSP 90 at Different Time-points in Rabbits with Myocardial Ischemia-reperfusion Injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) and moxibustion (Moxi) pretreatment on expression of myocardial heat shock protein (HSP) in acute myocardial ischemia-reperfusion injury (MIRI) rabbits. METHODS: A total of 72 New Zealand rabbits were randomly divided into 4 groups:sham operation, MIRI model, EA pretreatment and Moxi pretreatment (n=18 rabbits in each group) which were further divided into 0, 24 and 48 h (time-point) subgroups (n=6 in each). The MIRI model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 40 min and reperfusion for 60 min. EA and Moxi stimulation was respectively applied to bilateral "Neiguan"(PC 6) for 20 min, once daily for 5 days before ADB occlusion. The expressions of myocardial HSP 27, HSP 70 and HSP 90 were detected by immunohistochemistry. The pathological and ultrastructural changes of left ventricular ischemia tissue were observed under light and transmission electronic microscope (TEM), respectively. RESULTS: Outcomes of H.E. staining and ultrastructure showed that MIRI-induced changes of disordered arrangement of cardiomyocytes, vague myocardial transverse striation, inflammatory infiltration, cardiac myofibre necrosis and fibrolysis (light microscope), and myofiber atrophy, vague and disorder in the arrangement of myofiber, myofilament necrosis, interstitial edema, mitochondrial swelling, microvessel expansion, etc. (TEM) were relatively milder in both EA and Moxi pretreatment groups (48 h). In comparison with the sham group, the expression levels of myocardial HSP 27, HSP 70 and HSP 90 had no significant changes after MIRI at the 3 time-points (P>0.05). In the pretreatment groups, the expression levels of HSP 27 at 24 and 48 h in both EA and Moxi groups, HSP 70 at 48 h in both groups, HSP 70 at 0 and 24 h in the Moxi group were significantly up-regulated compared with the model group (P<0.05, P<0.01). No significant changes were found in the expression of HSP 90 at the 3 time-points in the EA and Moxi pretreatment groups (P>0.05). No significant differences were found between EA and Moxi in up-regulating expressions of myocardial HSP 27, HSP 70 and HSP 90 proteins at the 3 time-points (P>0.05) except HSP 70 at 24 h (Moxi being stronger relative to EA, P<0.05). CONCLUSIONS: EA and Moxi pretreatment has a protective effect on ischemic myocardium in MIRI rabbits, which Feb be associated with their actions in up-regulating myocardial HSP 27 and HSP 70 expression.

Comparison of perceptual eye positions among patients with different degrees of anisometropia.

The aim of this study is to compare the perceptual eye positions (PEPs) among patients with different degrees of anisometropia.A total of 157 patients were recruited into this retrospective study. A detailed ophthalmic examination was conducted on each patient. The degree of refractive errors in the presence of astigmatism was converted into the degree of spherical equivalent (SE). Patients were divided into 3 groups according to the interocular SE difference: severe anisometropia group with interocular SE difference ≥2.50D, mild anisometropia group with interocular SE difference ≥1.00D and <2.50D, and non-anisometropia group with interocular SE difference <1.00D. The vertical and horizontal PEP were measured by a computer-controlled perceptual examination evaluation system. The results obtained from the 3 groups were compared and analyzed.A total of 157 patients were enrolled including 32 patients in the severe anisometropia group, 37 patients in the mild anisometropia group, and 88 patients in the non-anisometropia group. The quartiles of vertical PEP pixels were as follows: 7.50 (5.00, 16.75) in the severe anisometropia group, 5.00 (2.00, 7.50) in the mild anisometropia group, and 5.00 (3.00, 9.00) in the non-anisometropia group, respectively. The vertical PEP pixel was much higher in the severe anisometropia group than that in the other two groups (P < .05). The quartiles of horizontal PEP pixels were as follows: 27.50 (10.75, 67.50) in the severe anisometropia group, 17.00 (7.00, 54.50) in the mild anisometropia group, and 21.50 (11.00, 60.75) in the non-anisometropia group. There were no statistically significant differences among the 3 groups (P > .05).There was an obvious deviation of vertical PEP in patients with anisometropia ≥2.50D, indicating that the instability of vertical PEP might be associated with the development of severe anisometropia.

Development of a highly reliable assay for ubiquitin-specific protease 2 inhibitors.

The dynamic modification of proteins with ubiquitin plays crucial roles in major celluar functions, and is associated with a number of pathological conditions. Ubiquitin-specific proteases (USPs) cleave ubiquitin from substrate proteins, and rescue them from proteasomal degradation. Among them, USP2 is overexpressed and plays important roles in various cancers including prostate cancer. Thus, it represents an attractive target for drug discovery. In order to develop potent and selective USP2 inhibitors, a highly reliable assay is needed for in-depth structure-activity relationship study. We report the cloning, expression, and purification of USP2 and UBA52, and the development of a highly reliable assay based on readily available SDS-PAGE-Coomassie systeme using UBA52 as the substrate protein. A number of effective USP2 inhibitors were also identified using this assay.

Knockdown of calponin 2 suppressed cell growth in gastric cancer cells.

Calponin family members are actin filament-associated regulatory proteins with distinct expression patterns. Previous studies on CNN2 (calponin 2) have demonstrated that CNN2 is expressed in a broad range of tissues and cell types, exhibiting potential regulatory roles in a number of cellular activities, including cell proliferation, cell migration, and platelet adhesion. In this work, we found that both messenger RNA and protein expression levels of CNN2 were remarkably upregulated in 60%-70% of gastric cancer tissues by comparison with those of neighboring non-tumorous mucosa. By utilizing specific shCNN2 (small hairpin RNA targeting CNN2), the potential role of CNN2 in regulating AGS gastric cancer cell growth was then further investigated. AGS cells infected with shCNN2 exhibited significantly decreased cell growth ability by comparison with control cells in vitro. Moreover, while there was no obvious difference in cell cycle distribution between two groups, enhanced cell apoptosis was detected in cells with reduced CNN2 expression. Consistently, caspase 3/7 activity was also remarkably activated upon shCNN2 lentivirus infection. Taken together, our results demonstrated that knockdown of endogenous CNN2 in AGS cells could significantly activate cell apoptosis pathway and therefore suppress cell growth in vitro. The deletion of CNN2 might be a potential therapeutic approach to inhibit aggressive growth of gastric cancer.