[Relationship between expression of NLRP3 inflammasome and improvement of macular structure in patients with wet age-related macular degeneration after anti-vascular endothelial growth factor therapy].

Objective: To explore the relationship between expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and improvement of macular structure in patients with wet age-related macular degeneration (wAMD) after anti-vascular endothelial growth factor (VEGF) therapy. Methods: A before-after study was carried out. A total of 110 patients (110 eyes) with wAMD who were admitted to Department of Ophthalmology, People's Hospital Affiliated to Shandong First Medical University between August 2019 and December 2021 were enrolled, and all patients were given vitreous injection of anti-VEGF drug (ranibizumab or bevacizumab). The aqueous humor was collected to detect mRNA levels of NLRP3, cysteinyl aspartate specific protease-1 (Caspase-1), apoptosis-associated speck-like protein (ASC) and interleukin (IL) 1ß by fluorescence quantitative PCR. The levels of IL-1ß, IL-18, tumor necrosis factor α (TNF-α) and VEGF in aqueous humor were detected by enzyme-linked immunosorbent assay (ELISA). The correlation between the above indexes and central macular thickness (CMT) in wAMD patients was analyzed by multivariate linear regression analysis. Results: In the 110 wAMD patients, there were 68 males and 42 females, with a mean age of (68.7±7.6) years. Compared with those before treatment, mRNA levels of NLRP3 (1.65±0.27, 1.34±0.19 vs 1.97±0.23, both P<0.017), Caspase-1 (1.47±0.15, 1.29±0.17 vs 1.53±0.18, both P<0.017), ASC (1.33±0.14, 1.21±0.18 vs 1.47±0.12, both P<0.017) and IL-1ß (1.78±0.21, 1.46±0.17 vs 2.21±0.24, both P<0.017), and levels of IL-1ß [(26.9±5.7), (20.3±4.6) vs (33.6±8.3) ng/L, both P<0.017], IL-18 [(32.7±7.6), (23.3±6.9) vs (46.4±9.4) ng/L, both P<0.017], TNF-α [(39.4±6.6), (21.7±6.3) vs (52.9±9.1) ng/L, both P<0.017] and VEGF [(35.7±10.2), (23.4±6.7) vs (65.4±19.3) ng/L, both P<0.017] were decreased after the first and second injection. Moreover, the above-mentioned indexes after second injection were lower than those after the first injection (all P<0.017). The results of multivariate linear regression analysis showed that NLRP3 mRNA (the first injection: ß=53.750, P<0.001; the second injection: ß=94.648, P<0.001), IL-1ß (the first injection: ß=1.356, P=0.021; the second injection: ß=2.008, P=0.003), IL-18 (the first injection: ß=1.984, P<0.001; the second injection: ß=1.251, P=0.003) and VEGF (the first injection: ß=1.875, P<0.001; the second injection: ß=2.119, P<0.001) had linear relationships with CMT. Conclusion: The decrease of NLRP3 inflammasome and its products in aqueous humor may be related to the improvement of macular structure in wAMD patients after anti-VEGF therapy.

[Expression of cartilage oligomeric matrix protein in the synovial chondromatosis of the temporomandibular joint].

OBJECTIVE: To detect the expression of cartilage oligomeric matrix protein (COMP) in the synovial chondromatosis of the temporomandibular joint (TMJSC), and to discuss the possible interactions between COMP, transforming growth factor (TGF)-ß3, TGF-ß1 and bone morphogenetic protein-2 (BMP-2) in the development of this neoplastic disease. METHODS: Patients in Peking University School and Hospital of Stomatology from January 2011 to February 2020 were selected, who had complete medical records, TMJSC was verified histologically after operation. The expressions of COMP, TGF-ß3, TGF-ß1 and BMP-2 in the TMJSC of the temporomandibular joint were detected by immunohistochemistry and quantitative real-time PCR (RT-PCR) at the protein level and mRNA level respectively, compared with the normal synovial tissue of temporomandibular joint. The histological morphology, protein expression and distribution of TMJSC tissues were observed microscopically, and the positive staining proteins were counted and scored. SPSS 22.0 statistical software was used to analyze the expression differences between the related proteins in TMJSC tissue and the normal synovial tissue of temporomandibular joint and to compare their differences. P < 0.05 indicated that the difference was statistically significant. RESULTS: Immunohistochemical results showed that the positive expression of COMP in TMJSC tissues was mostly found in synovial tissues and chondrocytes adjacent to synovial tissues, and the difference was statistically significant, compared with the normal temporomandibular joint synovial tissues. The positive expression of COMP was significantly different between recurrent TMJSC and non-recurrent ones. The positive expressions of TGF-ß3, TGF-ß1 and BMP-2 were higher than the normal synovial tissue, and were also mostly found in the synovial cells and adjacent chondrocytes, which was further confirmed by Western blot. According to the RT-PCR results, the expressions of COMP, TGF-ß3, TGF-ß1 and BMP-2 in TMJSC were higher than those in the normal synovial tissue. CONCLUSION: The expression of COMP in TMJSC of temporomandibular joint increased significantly, compared with the normal synovial tissue. There may be interactions between COMP and cytokines related to the proliferation and differentiation, like TGF-ß3, TGF-ß1 and BMP-2, which may play a potential role in the pathogenesis of TMJSC.

Superconducting Open-Framework Allotrope of Silicon at Ambient Pressure.

Diamond Si is a semiconductor with an indirect band gap that is the basis of modern semiconductor technology. Although many metastable forms of Si were observed using diamond anvil cells for compression and chemical precursors for synthesis, no metallic phase at ambient conditions has been reported thus far. Here we report the prediction of pure metallic Si allotropes with open channels at ambient pressure, unlike a cubic diamond structure in covalent bonding networks. The metallic phase termed P6/m-Si_{6} can be obtained by removing Na after pressure release from a novel Na-Si clathrate called P6/m-NaSi_{6}, which is predicted through first-principles study at high pressure. We identify that both P6/m-NaSi_{6} and P6/m-Si_{6} are stable and superconducting with the critical temperatures of about 13 and 12 K at ambient pressure, respectively. The prediction of new Na-Si and Si clathrate structures presents the possibility of exploring new exotic allotropes useful for Si-based devices.

Role of COL9A1 genetic polymorphisms in development of congenital talipes equinovarus in a Chinese population.

Talipes equinovarus is a common congenital deformity. COL9A1 polymorphisms are associated with the development of articular cartilage-related diseases. In the current study, we evaluated the relationship between COL9A1 rs1135056, rs35470562, and rs592121 genetic polymorphisms and risk of congenital talipes equinovarus. Between January 2013 and July 2015, 87 children with congenital talipes equinovarus and 174 control subjects were recruited from the Fourth People's Hospital of Shaanxi and the First Hospital of Yulin. Genotyping of COL9A1 rs1135056, rs35470562, and rs592121 was performed using polymerase chain reaction-restriction fragment length polymorphism. Using conditional regression analysis, the AA genotype of COL9A1 rs35470562 was found to be significantly associated with increased risk of congenital talipes equinovarus compared to the GG genotype [odds ratio (OR) = 2.60, 95% confidence interval (CI) = 1.06-6.32]. In addition, under a recessive model, rs35470562 AA carriers were observed to be at higher risk for this condition in comparison to individuals with GG or GA genotypes (OR = 2.23, 95%CI = 1.03-5.04). However, no significant relationship was established between the COL9A1 rs1135056 and rs592121 polymorphisms and congenital talipes equinovarus in any of the genetic models tested. In conclusion, our results indicate that the COL9A1 rs35470562 variant may contribute to congenital talipes equinovarus susceptibility in the Chinese population examined.

[Association and interaction of pre-pregnant body mass index and gestational weight gain of women on neonatal birthweight].

Objective: To investigate the association between maternal pre-pregnant body mass index and gestational weight gain, as well as their interaction on neonatal birthweight. Methods: We built a cohort in Anqing Municipal Hospital from January 2014 to March 2015, enrolling pregnant women who decided to give birth in this hospital. All women were asked to fill a questionnaire for basic information collection. Medical information of both pregnant women and their newborns were obtained through electronic medical record. Chi-square analysis, multinomial logistic regression, multiplicative and additive interaction methods were used to analyze the association between pre-pregnant body mass index and gestational weight gain as well as their interactions on birth weight of the neonates. Results: A total of 2 881 pregnant women were included in this study. Of the 2 881 newborns, 359 (12.46%) were small for gestational age (SGA) and 273 (9.48%) were large for gestational age (LGA). After adjusting the possible confounding factors, results from the multinomial logistic regression showed that pre-pregnancy underweight women were more possible to deliver SGA (aRR=1.33, 95%CI: 1.02-1.73). If the gestational weight gain was below the recommended criteria, the risk of SGA (aRR=1.64, 95%CI: 1.23-2.19) might increase. Pre-pregnancy overweight/obese could increase the risk of being LGA (aRR=1.86, 95%CI: 1.33-2.60). Maternal gestational weight gain above the recommendation level was associated with higher rates of LGA (aRR=2.03, 95%CI: 1.49-2.78). Results from the interaction analysis showed that there appeared no significant interaction between pre-pregnancy BMI and gestational weight on birthweight. Conclusion: Pre-pregnancy body mass index and gestational weight gain were independently associated with neonatal birthweight while pre-pregnancy BMI and gestational weight gain did not present interaction on birthweight.

Boron Triangular Kagome Lattice with Half-Metallic Ferromagnetism.

Based on the first-principles evolutionary materials design, we report a stable boron Kagome lattice composed of triangles in triangles on a two-dimensional sheet. The Kagome lattice can be synthesized on a silver substrate, with selecting Mg atoms as guest atoms. While the isolated Kagome lattice is slightly twisted without strain, it turns into an ideal triangular Kagome lattice under tensile strain. In the triangular Kagome lattice, we find the exotic electronic properties, such as topologically non-trivial flat band near the Fermi energy and half-metallic ferromagnetism, and predict the quantum anomalous Hall effect in the presence of spin-orbit coupling.

[Influence of intrahepatic cholestasis during pregnancy on the incidence of preterm birth].

Objective: Intrahepatic cholestasis during pregnancy (ICP) and its relation to incidence of preterm birth (PTB) were under study. Methods: A prospective cohort study was carried out that including all the hospitalized pregnant women with live singleton births, from January 2014 to March 2015 in Anqing Municipal Hospitals. Informed consent was followed in every pregnant woman with related demographic information collected through questionnaire and hospital electronic medical record system. Both univariate and multi-variate statistical methods were used to analyze the relations between ICP and incidence of PTB. Results: A total of 2 758 pregnant women were included in this study. The incidence proportions of ICP and PTB appeared as 7.25% and 16.28% respectively. Results from the logistic regression analysis showed that ICP increased the risk of both overall PTB (RR=2.33, 95%CI: 1.67-3.25) and medically indicated PTB (RR=8.46, 95%CI: 5.45-13.12), but not the spontaneous PTB (RR=0.94, 95%CI: 0.57-1.54). Conclusion: ICP seemed to have increased the risk on medically indicated PTB but not the spontaneous PTB.

[Comparison of results of two immunoassays for detection of hepatitis B surface antigen in pregnant women].

Objective: To evaluate and compare the detection consistency of hepatitis B surface antigen (HBsAg) by two immunoassays: enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescent immunoassay (ECLIA). Methods: A prospective study was conducted among 2 296 pregnant women recruited consecutively from January 1, 2014 to January 31, 2015 in a hospital. Blood samples were collected from them for the detection of HBsAg by using ELISA and ECLIA, Kappa test was performed on the results. Nested polymerase chain reaction and sequencing of HBV S gene were also performed in all samples. Phylogenetic analysis was performed using Mega 6.0 software. Results: The two methods had high detection consistence of HBsAg (Kappa=0.71). There were significant differences in detection result of B genotype and adw2 serotype HBV strains between two methods. Among 123 identified HBV strains, 113 belonged to genotype B and available for further analysis. The difference in detection of substitution rates between two methods or different positive groups were not significant. Compared with ELISA single positive group, the ECLIA single positive group had completely different substitution sites. Conclusion: The two methods had high detection consistence of HBsAg, but there were still 32.4% HBV DNA positive cases in ELISA/ECLIA single positive group, and complete complementary substitution sites between ELISA single positive group and ECLIA single positive group. Our results suggested that more effective detection procedure should be considered for the possible impact of the HBV silent transmission and infection.

Are medical students adequately trained to prescribe at the point of graduation? Views of first year foundation doctors.

BACKGROUND: Drugs are the major therapeutic intervention provided by most doctors throughout their careers. The General Medical Council expects all medical students to be competent to prescribe at the point of graduation. AIMS: The aim of this study was to assess the views of Foundation Year 1 (FY1) doctors who had recently graduated from the University of Edinburgh about their training and competence in relation to the use of drugs based on their early clinical experience. METHOD: A questionnaire was constructed based on Tomorrow's Doctors 2002 and distributed to FY1 doctors who graduated in August 2005. RESULTS: Responses were received from 100 (39.8%) of the doctors who graduated in 2005. Only 32% respondents considered themselves 'competent to prescribe' at the point of graduation. Less than 50% of respondents felt comfortable in providing information about possible treatments to allow patients to make informed decisions about their care. The majority of respondents complained about a lack of formal teaching and practice at basic clinical skills relating to drug therapy. CONCLUSION: Many graduates feel under-prepared to take on prescribing responsibilities after graduation. These findings emphasise the need to ensure that all medical curricula are able to provide sufficient learning opportunities and robust assessment in this important area of clinical practice.

Effect of zinc supplementation on plasma high-density lipoprotein cholesterol and zinc.

The recent report by Hooper PL, et al. (JAMA 1980;244:1960-1) that pharmacological doses (160 mg) of zinc lowered high-density lipoprotein (HDL)-cholesterol in men and that zinc might be an atherogenic agent prompted this report of the effect of zinc supplementation on HDL-cholesterol in women. Four levels of zinc supplements (0, 15, 50, or 100 mg/day) were given to 32 women for 8 wk. Fasting plasma HDL-cholesterol and zinc were measured at biweekly intervals. Plasma zinc increased in the supplemented groups, peaked at wk 4, then decreased toward initial values. The decline in plasma zinc regardless of continuing zinc administration may reflect a homeostatic response. No significant differences were seen in HDL-cholesterol over the 8 wk except in the 100 mg group at wk 4 when a transient decrease, -8.4% (57 to 48 mg/dl, p less than 0.04) was observed. Thus we conclude that in women the reduction in HDL-cholesterol in response to the pharmacological doses of zinc used in this study was transient and not dose-related.

Role of endogenous endothelin and nitric oxide in tubuloglomerular feedback.

To elucidate the roles of endogenous endothelin (ET) and nitric oxide (NO) in tubuloglomerular feedback (TGF), the effects of FR139317, a specific ET-A receptor antagonist, and NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor on TGF were studied in Sprague-Dawley rats. FR139317 (1.5 mg/kg/hr i.v.) reversed the systemic pressor and renal vasoconstrictor responses induced by ET-1 (2 nmol/kg/hr i.v.), but did not alter the early proximal flow rate (EPFR) reduction in response to a loop perfusion with an artificial tubular fluid at 40 nl/min (47 +/- 3 vs. 47 +/- 3% in controls). L-NNA (0.2 mg/kg + 2 micrograms/kg/min i.v.) had no effect on systemic blood pressure (BP), renal hemodynamics or EPFR measured at zero perfusion (31 +/- 2 vs. 31 +/- 2 nl/min in controls), but enhanced the EPFR reduction during loop perfusion to 77 +/- 3%. Loop perfusion with 10(-3) M L-NNA in perfusate also increased the EPFR reduction to 70 +/- 7%. In conclusion, inhibition of NO synthesis enhances the TGF-mediated reduction of nephron GFR. This indicates an active participation of endogenous NO in the control of afferent arteriolar tone. endogenous ET does not influence TGF via the ET-A receptor.

Comparison of effectiveness of vaginal and abdominal routes in treating severe uterovaginal or vault prolapse.

INTRODUCTION: This study compares the efficacy of abdominal and vaginal routes in correcting severe uterovaginal or vault prolapses by examining their primary surgical outcomes. METHODS: A retrospective study was conducted on operations performed from March 1998 to December 2001. The classifications of uterovaginal prolapse and vault prolapse were based on the Halfway system. It involved 177 women with at least grade 4 uterovaginal prolapse or grade 3 vault prolapse, and had undergone vaginal sacrospinous ligament fixation or abdominal sacrocolpopexy. The subjects were divided into two groups: 113 women who had an abdominal sacrocolpopexy and 64 women who had a vaginal sacrospinous ligament fixation. The primary surgical outcome measures was classified as cured, improved or failure according to our definition at their last follow-up. RESULTS: The abdominal sacrocolpopexy group had significantly greater intra-operative blood loss, operating time, haematuria, longer postoperative catheterisation and hospitalisation. Vaginal sacrospinous ligament fixation had more suture erosion. 95.6 percent of women with abdominal sacrocolpopexy were cured compared to 79.7 percent with vaginal sacrospinous ligament fixation. Five (4.4 percent) patients in the abdominal sacrocolpopexy group and six (9.4 percent) in the vaginal sacrospinous ligament fixation group defaulted their six-month follow-up with a mean follow-up of 18.1 months (range 0.9-48.1 months) and 13.2 months (range 1.1-29.1 months), respectively. CONCLUSION: Abdominal sacrocolpopexy is more effective in correcting severe uterovaginal or vault prolapses but it is associated with higher intra- and post-operative morbidity compared to vaginal sacrospinous ligament fixation. Vaginal sacrospinous ligament fixation is preferred in patients with medical disorders.

[Microcirculation in renal interstitium].

Microcirculation in the renal interstitium plays an important role in the regulation of urinary sodium excretion and thus in the control of blood pressure. An increase in renal interstitial hydrostatic pressure caused by renal perfusion pressure elevation induces pressure natriuresis by decreasing tubular reabsorption. Chronic NO inhibition in the medullary interstitium decreases medullary blood flow and induces sodium retention and blood pressure elevation. Chronic medullary, but not intravenous, infusion of ACE inhibitor restores the impaired pressure natriuresis by improving medullary microcirculation in SHR. The tubuloglomerular feedback signal transmission is dependent on Cl concentration in the juxtaglomerular interstitium and its sensitivity is modulated by pressure there in.

Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling.

Dishevelled (Dvl) is a key regulator of Wnt signaling both in the canonical and non-canonical pathways. Here we report the identification of a regulatory domain of ubiquitination (RDU) in the C-terminus of Dvl. Mutations in the RDU resulted in accumulation of polyubiquitinated forms of Dvl, which were mainly K63 linked. Small interfering RNA-based screening identified Usp14 as a mediator of Dvl deubiquitination. Genetic and chemical suppression of Usp14 activity caused an increase in Dvl polyubiquitination and significantly impaired downstream Wnt signaling. These data suggest that Usp14 functions as a positive regulator of the Wnt signaling pathway. Consistently, tissue microarray analysis of colon cancer revealed a strong correlation between the levels of Usp14 and ß-catenin, which suggests an oncogenic role for Usp14 via enhancement of Wnt/ß-catenin signaling.

Renal effects of efonidipine hydrochloride, a new calcium antagonist, in spontaneously hypertensive rats with glomerular injury.

1. To obtain some insight into the renoprotective mechanism of the new calcium antagonist efonidipine hydrochloride, we evaluated the acute effects of efonidipine on proteinuria, glomerular haemodynamics and the tubuloglomerular feedback (TGF) mechanism in anaesthetized 24-25-week-old spontaneously hypertensive rats (SHR) with glomerular injury. 2. Efonidipine infusion at 10 micrograms/kg per h following a bolus dose of 10 micrograms/kg, i.v., reduced systemic blood pressure (BP) and renal vascular resistance, whereas renal plasma flow (RPF), glomerular filtration rate (GFR), filtration fraction, urine volume and urinary sodium excretion were unaltered. Urinary protein excretion was clearly diminished from 163 +/- 25 to 105 +/- 24 ng/min per g kidney weight. 3. Micropuncture experiments revealed that the maximal reduction of proximal stop-flow pressure (SFP), an index of glomerular capillary pressure (Pgc), induced by loop of Henle perfusion was significantly less with efonidipine treatment (6.7 +/- 1.0% of SFP with no loop flow) than in control (23.8 +/- 3.1%). In the presence of efonidipine, SFP at half-maximal reduction (SFP1/2max), which approximates Pgc at the in vivo steady state tubular flow rate, remained unchanged compared with control (36.9 +/- 0.8 vs 35.3 +/- 0.7 mmHg, respectively) and the slope of dependency on mean BP was not different between control and efonidipine. 4. These results indicate that efonidipine attenuates the TGF response in SHR by dilating the afferent arteriole, thus maintaining the level of RPF and GFR despite reduced renal perfusion pressure. Constant GFR and SFP1/2max under efonidipine suggest that single nephron GFR and Pgc remain unaltered and that a marked reduction in proteinuria is achieved without changes in single nephron GFR or Pgc of superficial nephrons.

Effects of an angiotensin II receptor antagonist, TCV-116, on renal haemodynamics in essential hypertension.

The renal effects of a nonpeptide angiotensin II receptor antagonist, TCV-116, were investigated in 12 hospitalised patients with mild-to-moderate essential hypertension. After a 2-week placebo period, TCV-116 was given for 2 weeks in increasing doses from 4 mg to 8 mg daily to normalise the mean blood pressure. Blood pressure fell from 156 +/- 9/93 +/- 3 mmHg at the end of the placebo period to 140 +/- 9/85 +/- 4 mmHg after TCV-116 treatment. The pulse rate was unchanged. Renal vascular resistance fell from 1.62 +/- 0.20 to 1.37 +/- 0.17 dyne.s.cm-5 . 1.48 m2 x 10(4), renal plasma flow increased from 329 +/- 19 to 367 +/- 27 mL.min-1.1.48 m-2, and GFR was unchanged despite a fall in renal perfusion pressure. TCV-116 reduced the filtration fraction from 0.302 +/- 0.019 to 0.258 +/- 0.009, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium, potassium, and urate did not change. An increase in plasma renin activity (from 1.1 +/- 0.3 to 2.2 +/- 0.7 ng.mL-1.h-1) and a fall in the plasma aldosterone concentration (from 6.2 +/- 0.8 to 4.5 +/- 0.7 ng.dL-1) were also seen. These results indicate that TCV-116 has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension.