[Research progress on the correlation between cirrhosis and frailty].

Frailty, which predicts high dependency and mortality, is a major challenge for healthcare systems in nations that are rapidly aging and is receiving increasing attention. Cirrhosis is often combined with frailty, which has a significant impact on patient health outcomes. Understanding the risk factors for frailty, elucidating the mechanism of cirrhosis combined with frailty, and early recognition and slowing down the occurrence and development of frailty are of great significance for the prognosis of cirrhotic patients. This article reviews the current research status of cirrhosis combined with frailty, including the definition and risk factors, mechanism, correlation, and intervention measures, in order to improve understanding and provide assistance for strengthening early identification, management, and intervention.

[Research progress on the relationship between liver cirrhosis and thyroid hormones].

There exists a complex relationship between liver and thyroid hormones. Liver plays an important role in the activation, inactivation, transportation, and metabolism of thyroid hormones. At the same time, thyroid hormones also affect hepatocytes activity and liver metabolism, such as lipid and bilirubin metabolism. Importantly, thyroid hormone levels often change abnormally in patients with liver cirrhosis. Therefore, studying the change of thyroid hormone levels in patients with liver cirrhosis has a certain clinical value for assessing the severity, prognosis, diagnosis and treatment. This paper reviews the research progress on the relationship between liver cirrhosis and thyroid hormone.

[Association between pulse pressure and new-onset diabetes in hypertensive patients].

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q1-Q4), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q1 group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q2 group(41-<51 mmHg) (n=8 196); Q3 group (51-<61 mmHg) (n= 8 270); Q4 group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.

[The rotational stability of Toric intraocular lenses and influencing factors in cataract patients with different axial length].

Objective: To evaluate the rotational stability of the Toric intraocular lens (TIOL) and influencing factors in cataract patients with different axial length. Methods: This retrospective cohort study consecutively enrolled patients who had phacoemulsification and AcrySof TIOL implantation in Peking University Third Hospital from May 2018 to January 2019. Based on axial length, patients were divided into two groups. Group A consisted of patients whose axial length was ≤ 24 mm. Patients whose axial length was >24 mm were included in group B. Data at three months postoperatively were used to evaluate the rotational stability of TIOL and its correlation with axial length, corneal white to white distance, lens thickness and TIOL spherical power. And t test, nonparametric test, chi-square test and Spearman test were used for statistical analysis. Results: Group A enrolled 39 patients (17 males and 22 females), with a median age of 74 years (range, 36-86 years). Group B enrolled 26 patients (11 males and 15 females), with a median age of 68 years (range, 36-86 years). For the efficacy of TIOL, in group A, the best corrected distance visual acuity (BCDVA, logarithm of the minimum angle of resolution) was 0.30 (0.10, 1.00) preoperatively and 0.10 (0.00, 0.60) postoperatively, and the astigmatism was 2.11 (0.95, 5.10) D preoperatively and 1.00 (0.00, 1.75) D postoperatively. In group B, the BCDVA was 0.36 (0.05, 1.00) preoperatively and 0.05 (0.00, 0.40) postoperatively, and the astigmatism was 2.00 (0.78, 3.76) D preoperatively and 0.75 (0.00, 2.25) D postoperatively. Between group A and group B, there were no significant differences in BCDVA (P=0.604) and astigmatism (P=0.789) preoperatively.In these two groups, postoperative BCDVA and astigmatism both significantly improved compared to preoperative parameters (both P<0.01). Between group A and group B, there were no significant differences in BCDVA (P=0.536) and astigmatism (P=0.076) postoperatively. In terms of rotational stability, the rotation in group A was 5.15°±3.62°, and that in group B was 6.50°±4.66°. There was no statistical difference between two groups (P=0.195). As for predictability, the percentage of eyes with rotation ≤5° was 59.0% (23 eyes) in group A and 50.0% (13 eyes) in group B. There was no statistical difference between the two groups (P=0.647). There was no significant correlation between the rotational stability of TIOL and axial length, corneal white to white distance, lens thickness or TIOL spherical power (P=0.836, 0.568, 0.170, 0.365). Conclusions: The rotational stability of TIOL at three months postoperatively in patients whose axial length >24 mm is of no difference with patients whose axial length ≤ 24 mm. It has no correlation with axial length, corneal white to white distance, lens thickness and TIOL spherical power. (Chin J Ophthalmol, 2020, 56: 41-46).

Granzyme B-truncated VEGF fusion protein represses angiogenesis and tumor growth of OSCC.

OBJECTIVE: To evaluate the antitumor effects of fusion protein hGrB-TV of human granzyme B (hGrB) and truncated vascular endothelial growth factor (tVEGF) on human oral squamous cell carcinoma (OSCC) in vitro and in vivo. METHODS: The fusion protein hGrB-TV was expressed and purified from E. coli bacteria by affinity chromatography. The cytotoxcity of hGrB-TV on VEGFR-2 (Flk-1)(+) OSCC cells was analyzed in vitro. The antitumor therapeutic study was conducted on OSCC xenografts in vivo. RESULTS: The purified hGrB-TV fusion protein was selectively internalized into VEGFR-2 (Flk-1)(+) OSCC cells and endothelial cells. It can cleave inactive caspase 3 into its active p20 form. The hGrB-TV showed dose-dependent cytotoxicity on VEGFR-2(+) SCC-9 cells. The morphological changes and cytolysis were appeared within dozen minutes. However, no cytotoxicity was observed on VEGFR-2(-) cells. The hGrB alone or tVEGF alone did not have any toxicity on SCC-9 cells. In addition, hGrB-TV treatment completely destroyed the vasculature of the chick chorioallantoic membrane (CAM) in vivo and consequently led to chick embryo development arrest. Most importantly, the fusion protein hGrB-TV inhibited tumor angiogenesis and growth of human OSCC xenografts in nude mice without any apparent toxicity. CONCLUSIONS: The fusion protein hGrB-TV specifically inhibits angiogenesis and tumor growth of OSCC; hGrB-TV is a powerful and safe therapeutic molecule for tumor therapy.

[Target cells of cytotoxic T cells in severe aplastic anemia in vitro].

OBJECTIVE: To clarify the specific target of severe aplastic anemia (SAA) immune attack via identifying the target cells of cytotoxic T cell attacks and the expression of apoptosis ligand on each department and each stage of bone marrow hematopoietic cells. METHODS: A total of 15 SAA patients and 15 normal controls were recruited in the Department of Hematology, Tianjin Medical University General Hospital between March 2011 and March 2012. Factor associated suicide(Fas) protein expression of CD34(+) , CD14(+) , CD33(+) , and GlycoA(+) cells in bone marrow was detected by flow cytometry. The CD8(+) T cells of SAA patients and CD3(-) bone marrow mononuclear cells (BMMNC) of controls were sorted by immunomagnetic separation and co-cultured for 72 hours. The apoptosis rate of CD34(+) , CD14(+) , CD33(+) , and GlycoA(+) cells were measured with flow cytometry. RESULTS: The expression of Fas protein in CD34(+) cells in SAA patients (46.59%± 27.60%) was significantly higher than that in control group (8.89%±7.28%, P<0.01). The expressions of Fas protein in CD14(+) , CD33(+) and GlycoA(+) cells in SAA group(29.29%±9.23%, 46.88%±14.30%, 15.15%±9.26%) were lower than those in control group(51.25%±38.36%, 72.06%±39.88%, 50.38%±39.88%, all P<0.05). The apoptosis rates of CD34(+) , CD33(+) and CD14(+) cells in the experimental group (CD8(+) T cells of SAA patients co-cultured with CD3(-) BMMNC of controls: 55.43%±20.50%, 38.13%±20.10%, 61.87%±21.65%)were significantly higher than those of the control group (CD8(+) T cells of controls co-cultured with CD3(-) BMMNC of controls: 35.02%±13.95%, 23.44%±10.33%, 37.04%±22.41%, all P<0.05). CONCLUSIONS: Cytotoxic T cells in SAA patients may have a killing effect on hematopoietic stem/progenitor cells, and granulocytic and macrophagocytic cells from normal bone marrow. Moreover, Fas/Fas ligand-mediated apoptosis may play an important role in the immune pathogenesis of SAA. CD34(+) cells show markedly increased Fas protein expression, which may be the main target cells in the process of immune injury in SAA patients.

The mechanism of PDX in regulating cervical cancer HeLa cell proliferation and tumor formation.

OBJECTIVE: As a gynecological malignant tumor, cervical cancer tends to occur in younger patients. Furin is an important member of precursor protein convertase that may affect malignant tumor metastasis and neovascularization. Pancreatic duodenal homeobox (PDX), as a transcription factor, can inhibit Furin. This study intends to explore the impact of PDX on cervical cancer HeLa cell proliferation and mechanism. PATIENTS AND METHODS: PDX plasmid was transfected to cervical cancer HeLa cells. Cell proliferation, invasion, and migration were tested. HeLa cells were injected to Balb/c nude mice to observe the change of general status, tumor formation rate, tumor weight, and volume. RESULTS: PDX expression was gradually increased after PDX transfection following time extension. Cell proliferation, invasion, and migration in experimental group were significantly lower than those in normal control (p < 0.05). The nude mice injected with PDX transfected HeLa cells showed markedly better general status, with reducing rate of tumor formation, tumor weight and volume compared with control. CONCLUSIONS: PDX can suppress cervical cancer HeLa cell proliferation, cell invasion and migration, improve general status of tumor-bearing nude mice and reduce tumor weight and volume. Our data highlight the clinical benefits of PDX in inhibiting cervical cancer proliferation, invasion, and metastasis.

Ageing behavior of extruded Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr (wt.%) alloy containing LPSO phase and γ' precipitates.

The effect of long period stacking ordered (LPSO) phase and γ' precipitates on the ageing behavior and mechanical properties of the extruded Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr (wt.%) alloy was investigated. The results show that more ß' phases precipitate during ageing treatment in the LPSO phase containing alloy so that the LPSO phase containing alloy exhibits a higher age-hardening response than the γ' precipitates containing alloy. The precipitation strengthening induced by ß' precipitates is the greatest contributor to the strength of the peak-aged LPSO-containing alloys. Higher strength is achieved in γ' precipitates containing alloy due to the more effective strengthening induced by dense nanoscale γ' precipitates than LPSO phases as well as the higher volume fraction of coarse unrecrystallized grains with strong basal texture. The extruded alloy containing γ' precipitates after T5 peak-ageing treatment shows ultra-high tensile yield strength of 462 MPa, high ultimate tensile strength of 520 MPa, and superior elongation to failure of 10.6%.

Effect of 2,4-dichlorophenoxyacetic acid on callus induction and plant regeneration in anther culture of wheat (Triticum aestivum L.).

Anthers from a doubled-haploid line of spring wheat (Triticum aestivum L.) cv. Pavon 76 were plated in liquid P-4 medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D) at four concentrations (0.5, 1.0, 2.0, 4.0 mg/l) for 5, 10, 15, and 25 days before being transferred to another medium with the same or reduced 2,4-D concentrations for the remainder of the induction phase for a total of 45 days. Incubation with 0.5 mg/l 2,4-D for 45 days produced lower callus yield and plant regeneration, indicative of insufficient auxin for callus induction. Callus yield and regeneration frequencies were higher with 1.0 mg/l 2,4-D. With 2.0 or 4.0 mg/l 2,4-D, an induction period of 10 or 15 days was sufficient for initiation of callus development. The extended presence of 2-4 mg/l 2,4-D in the medium beyond the initiation phase was detrimental to plant regeneration. Thus optimal callus induction and plant regeneration could be obtained through manipulating the 2,4-D concentration and the duration of its presence in the induction medium.

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats.

For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.