Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema.

AIM: To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide (TA) in treating diabetic macular edema (DME) and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection. METHODS: Totally 67 DME patients (67 eyes) and 30 cataract patients (32 eyes) were enrolled as the DME group and the control group, respectively. The DME group was divided into the aflibercept group (34 cases) and the aflibercept combined with TA group (combined group, 33 cases). The aqueous humor of both groups was collected during the study period. The aqueous levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) were detected using a microsphere suspension array technology (Luminex 200TM). Aqueous cytokines, best-corrected visual acuity (BCVA), central macular thickness (CMT), and complications before and after treatment were compared between the aflibercept group and combined group. RESULTS: The concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group (all P<0.01). After 1mo of surgery, the concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group (all P<0.01). The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment (P<0.01). However, the difference was not statistically significant after 3mo of treatment (P>0.05). CONCLUSION: The cytokines VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor of DME patients are significantly increased. Aflibercept and aflibercept combined with TA have good efficacy in DME patients, can effectively reduce CMT, improve the patient's vision, and have high safety. Aflibercept combined with TA can quickly down-regulate the aqueous humor cytokines and help to relieve macular edema rapidly. However, the long-term efficacy is comparable to that of aflibercept alone.

PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice.

Prostaglandin F2α (PGF2α) is a luteolytic hormone that promotes parturition in mammals at the end of pregnancy by reducing progesterone secretion from the corpus luteum (CL). In rodents and primates, PGF2α rapidly converts progesterone to 20α-hydroxyprogesterone (20α-OHP) by promoting 20α-hydroxysteroid dehydrogenase (20α-HSD) expression. However, the specific mechanism of 20α-HSD regulation by PGF2α remains unclear. Casein Kinase 1α (CK1α) is a CK1 family member that regulates a variety of physiological functions, including reproductive development. Here, we investigated the effects of CK1α on pregnancy in female mice. Our experiments showed that CK1α is expressed in mouse CL, and its inhibition enhanced progesterone metabolism, decreased progesterone levels, and affected mouse embryo implantation. Further, CK1α mediated the effect of PGF2α on 20α-HSD in mouse luteal cells in vitro. Our results are the first to show that CK1α affects the 20α-HSD mRNA level by affecting the ERK signalling pathway to regulate the expression of the transcription factor SP1. These findings improve our understanding of PGF2α regulation of 20α-HSD.

Neuropsychological Features in Patients with General Paresis of the Insane at an Early Stage.

BACKGROUND This study aimed to explore the features of cognitive impairment in patients with neurosyphilis at the early stage of mild cognitive impairment (MCI). MATERIAL AND METHODS A total of 18 patients with asymptomatic neurosyphilis (ANS), 19 patients with neurosyphilis at the MCI stage (neurosyphilis-MCI), and 15 patients with neurosyphilis at the dementia stage (neurosyphilis-dementia) were enrolled. Cognitive function was evaluated using comprehensive rating scales. Tests of syphilis in blood and cerebrospinal fluid (CSF) were conducted, and white blood cell (WBC) counts and protein levels in CSF were measured. RESULTS Overall cognitive function and individual cognitive domains, including memory, language, visuospatial skill, and attention/executive function, were all significantly impaired in the neurosyphilis-MCI group compared with the ANS group, and were further impaired in the neurosyphilis-dementia group. Although there was no difference in serum rapid plasma regain (RPR) titer among the 3 groups, the number of patients with serum RPR titer ≥1: 32 in the neurosyphilis-MCI group was much higher than that in the ANS group. CSF RPR positive rate in the neurosyphilis-MCI group was significantly higher than that in the ANS group. The WBC count, protein level, and the rate of elevated protein level or increased WBC count in CSF did not differ among the 3 groups. CONCLUSIONS The feature of cognitive impairment of neurosyphilis-MCI patients displayed multiple-domain amnestic MCI. Perhaps there were extensive brain areas involved at the early stage, and a continuous neuroinflammatory process was through the different stages of neurosyphilis. Early diagnosis and treatment are very important for preventing the progression of general paresis of the insane.

Distinctive microbiota distribution from healthy oral to post-treatment apical periodontitis.

Post-treatment apical periodontitis (PoAP) occurs when root canal treatment has not adequately eliminated bacterial invasion and infection. Yet little is known about the bacterial composition and changes related to the etiology and pathogenesis of PoAP. In this study, clinical samples classified as root apex (HARD) and periapical granulation tissues (SOFT) were separately collected from 10 patients with PoAP. The microbiota of each sample was characterized by 16S rRNA gene sequencing, and the obtained dataset was coanalyzed with 20 NCBI sequence read archive (SRA) datasets of healthy oral (HO) and primary apical periodontitis (PAP). We observed 2522 operational taxonomic units (OTUs) belonging to 29 phyla, and all samples shared 86.5% of the sequence reads. The OTUs affiliated with Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria, were identified as core microbiota, which accounted for nearly 90% of 16S rRNA sequences in all samples. However, the principal coordinates analysis (PCoA) of the beta diversity demonstrated that the three periapical statuses have distinct microbial compositions. Compared with HO and PoAP, Actinomyces has a significantly increased abundance in PAP. The microbial diversities in PoAP were significantly lower than those in the HO and PAP (p<0.05). The relative abundance of most bacterial taxa was decreasing, except that Clostridia and Synergistia were increased. Furthermore, we explored the potential metabolic differences of the microbial communities by KEGG pathway prediction. We revealed that the microbiota of PoAP might have a more active metabolic capacity, including carbohydrate metabolism, energy metabolism, and enzyme cofactor/carrier biosynthesis (p<0.05). Our study revealed that invasion of opportunistic pathogens such as Clostridia and Synergistia might play a significant role in PoAP, thus guiding the further study of complex microbial-host interactions and the development of more effective diagnostic and therapeutic methods.

Evolution of associating liver partition and portal vein ligation for staged hepatectomy from 2012 to 2021: A bibliometric analysis. Review.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has become increasingly popular during the past few decades, and its indications have extended from patients with normal liver to post-chemotherapy patients and even patients with cirrhosis. However, few studies have assessed the publications in relation to ALPPS. METHODS: Web of Science was searched to identify studies related to ALPPS published from 2012 to 2021. The analysis was performed using the bibliometric package (Version 3.1.0) in R software. RESULTS: In total, 486 publications were found. These articles were published in 159 journals and authored by 2157 researchers from 694 organizations. The most prolific journal was Annals of Surgery (24 articles and 1170 citations). The most frequently cited article was published in Annals of Surgery (average citations, 72.7; total citations, 727). China was the most productive country for ALPPS publications but had comparatively less interaction with other countries. Both thematic evolution and co-occurrence network analysis showed low numbers of topics such as failure, resection, and safety among the publications but large numbers of highly cited papers on outcomes, prediction, mechanisms, multicenter analysis, and novel procedures such as liver venous deprivation. A total of 196 studies focused the clinical application of ALPPS, and most studies were IDEAL Stages I and II. The specific mechanism of ALPPS liver regeneration remains unclear. CONCLUSIONS: This is the first bibliometric analysis offering an overview of the development of ALPPS research publications. Our findings identified prominent studies, countries, institutions, journals, and authors to indicate the future direction of ALPPS research. The role of ALPPS in liver regeneration and the long-term results of ALPPS need further study. Future research directions include comparison of ALPPS with portal vein embolization, liver venous deprivation, and other two-stage hepatectomies as well as patients' quality of life after ALPPS.

[Translational research of the advancement of multidisciplinary intersection in acupuncture-moxibustion technology innovation].

At present, acupuncture and moxibustion widely spread around the world, and its development is closely rela-ted to multidisciplinary integration. Interdisciplinary approaches are of great concern to the innovation and promotion of acupuncture-moxibustion therapy. Acupuncture and moxibustion, combined with optics, electrics, magnetics, infrared ray, microwave and other technologies, create the advanced and practical instrument for diagnosis and treatment of acupuncture and moxibustion and have made important contribution to clinical and teaching work. In the paper, focusing on the unique advantages of the science of acupuncture and moxibustion, the application of interdisciplinary approaches was explored to the promotion of acupuncture-moxibustion technology in its innovation and development, while the existing problems and countermeasures are further considered in the translational process of acupuncture-moxibustion technology to clinical application.

Air tamponade in retinal detachment surgery followed by ultra-widefield fundus imaging system.

AIM: To report the surgical result of pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD) by ultra-widefield fundus imaging system. METHODS: Of 25 consecutive patients (25 eyes) with fresh primary RRD and causative retinal break and vitreous traction were presented. All the patients underwent PPV with air tamponade. Visual acuity (VA) was examined postoperatively and images were captured by ultra-widefield scanning laser ophthalmoscope system (Optos). RESULTS: Initial reattachment was achieved in 25 cases (100%). The air volume was >60% on the postoperative day (POD) 1. The ultra-widefield images showed that the retina was reattached in all air-filled eyes postoperatively. The retinal break and laser burns in the superior were detected in 22 of 25 eyes (88%). A missed retinal hole was found under intravitreal air bubble in 1 case (4%). The air volume was range from 40% to 60% on POD 3. A double-layered image was seen in 25 of 25 eyes with intravitreal gas. Retinal breaks and laser burns around were seen in the intravitreal air. On POD 7, small bubble without effect was seen in 6 cases (24%) and bubble was completely disappeared in 4 cases (16%). Small oval bubble in the superior area was observed in 15 cases (60%). There were no missed and new retinal breaks and no retinal detachment in all cases on the POD 14 and 1mo and last follow-up. Air disappeared completely on a mean of 9.84d postoperatively. The mean final postoperative best-corrected visual acuity (BCVA) was 0.35 logMAR. Mean final postoperative BCVA improved significantly relative to mean preoperative (P<0.05). Final VA of 0.3 logMAR or better was seen in 13 eyes. CONCLUSION: PPV with air tamponade is an effective management for fresh RRD with superior retinal breaks. The ultra-widefield fundus imaging can detect postoperative retinal breaks in air-filled eyes. It would be a useful facility for follow-up after PPV with air tamponade. Facedown position and acquired visual rehabilitation may be shorten.

The formation of zein-chitosan complex coacervated particles: Relationship to encapsulation and controlled release properties.

The complex coacervation between zein and chitosan (CS) as well as the relationship with the controlled release properties of their complex nanoparticles were studied. The factors influencing the nanoparticle formation between zein and CS, including solid to liquid ratio, zein to CS ratio and pH, were systematically investigated. The isothermal titration calorimetry (ITC) showed that zein-CS interaction was spontaneous exothermic process. The pH the higher was, the stronger the interaction between zein and CS. The mean particle sizes of ZCNPs were increased by enhanced turbidity between zein and CS (from 90.89 nm to 1368.77 nm). The morphology study showed that spherical particles and coacervate were obtained with the increased interaction between zein and CS. The release profiles of curcumin in vitro indicated that slight burst effect followed by slow release was observed after interacting CS. The ZCNPs at pH 4.0 exhibited smaller particle size (162.07 nm), more stable ζ-potential (49.7 mV), higher encapsulation efficiency (94.67%) and slower release rate. In conclusion, the stronger the interaction was, the lower the curcumin released from the nanoparticles in vitro, and the ZCNPs at pH 4.0 had better potential in oral delivery application.

[Multifocal electroretinography for therapeutic effect evaluation of intravitreal injection Lucentis for wet age-related macular degeneration].

OBJECTIVE: To evaluate the changes in retinal functions using multifocal electroretinography (mfERG) following intravitreal injection of Lucentis for treatment of wet age-related macular degeneration. METHODS: This prospective study was conducted in 14 patients (9 men and 5 women, 14 eyes) with wet age-related macular degeneration receiving treatment with intravitreal injections of ranibizumab (Lucentis) in our hospital between October, 2014 and January, 2016. All the patients received the treatment following a 1+PRN protocol and after the initial injection, the patients were followed up monthly for 6 months to decide if additional injections were needed. The corrected visual acuity and mfERG findings of the patients were assessed before and at l, 3 and 6 months after the initial injection. RESULTS: At the last follow-up, the patients received injections for a mean of 2.86∓1.58 times. The best corrected visual acuity (BCVA) at 1 month after the initial treatment was not significantly different from that before treatment (P=0.07), but showed significant improvements at 3 and 6 months (P<0.05). In mfERG, the implicit time of the 6 rings showed no significant decrease after the treatment, but the amplitude density of P1 and N1 in rings 1 and 2 improved significantly at 1, 3, and 6 months after the initial injection (P<0.05). CONCLUSION: Multifocal electroretinography can serve as a useful modality for evaluating visual function changes in patients receiving intravitreal injection of Lucentis for wet age-related macular degeneration.

Reliability and validity of PDQ-39: a quality-of-life measure for patients with PD in China.

UNLABELLED: The syndromes of Parkinson's disease (PD) have impacts on health-related quality of life (HRQL). The 39-item Parkinson's disease Questionnaire (PDQ-39) was the first specific and a consistent instrument for the evaluation of HRQL in PD patients. PURPOSE: To test the reliability and validity of Chinese version PDQ-39. METHODS: Hundred and twenty-six PD without cognitive impairment were enrolled. The Chinese version of SF-36 was used to evaluate the congruent validity of PDQ-39 between related domains. Both PDQ-39 and SF-36 scales were fulfilled by the patients themselves. RESULTS: Five of eight subscales of PDQ-39 met the acceptable standards of reliability (Cronbach's α coefficient >0.80), while the other three subscales (cognition, communication, and bodily discomfort) failed to reach the above standards as reported by the others. All the item-to-subscale correlations (range: 0.457-0.887) met the minimal acceptable item convergent validity criterion of 0.40 (P < 0.001). Correlation between PDQ-39 subscales and scales of the SF-36 had high negative correlations with a range of -0.759 to -0.124. Four of them had significant negative correlations (P < 0.0001). CONCLUSIONS: The Chinese version of PDQ-39 is a reliable and valid instrument for Chinese PD patients. It is recommended as the most appropriate HRQL tool for PD.

Can the positive aromatic ring be as π-electron donor in π-halogen bond? A MP2 theoretical investigation on the unusual π-halogen bond interaction between three-membered ring (BNN)3⁺ and X1X2 (X1, X2 = F, Cl, Br).

The unusual π-halogen bond interactions are investigated between (BNN)3⁺ and X1X2 (X1, X2 = F, Cl, Br) employing MP2 at 6-311 + G(2d) and aug-cc-pVDZ levels according to the "CP (counterpoise) corrected potential energy surface (PES)" method. The order of the π-halogen bond interactions and stabilities of the complexes are obtained to be (BNN)3⁺... F2 < (BNN)3⁺... ClF < (BNN)3⁺... Cl2 < (BNN)3⁺... BrCl < (BNN)3⁺... Br2 < (BNN)3⁺ ... BrF. at MP2/aug-cc-pVDZ level. The analyses of the Mulliken charge transfer, natural bond orbital (NBO), atoms in molecules (AIM) theory and electron density shifts reveal that the nature of the π-halogen bond interaction in the complexes of ClF, BrF and BrCl might partly be charge transfer from the delocalized π-HOMO orbital of (BNN)3⁺ to X1X2. This result suggests that the positive aromatic ring (BNN)3⁺ might act as a π-electron donor to form the π-halogen bond.

Expression of stromal cell-derived factor-1 in diabetic retinopathy.

BACKGROUND: Neovascularization can cause vision loss in proliferative diabetic retinopathy (PDR) and may be affected by many factors. Stromal cell-derived factor-1 (SDF-1) is a potent stimulator of angiogenesis. The study was aimed to investigate the expression of SDF-1 and its correlation with vascular endothelial growth factor (VEGF) in the eyes with diabetic retinopathy. METHODS: The levels of SDF-1 and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 41 eyes of 41 patients with PDR and 12 eyes of 12 patients with idiopathic macular hole (IMH). Vitreous fluid samples and fibrovascular preretinal membranes were obtained at vitrectomy. SDF-1 and VEGF were localized using immunohistochemistry. RESULTS: The vitreous concentration of VEGF was significantly higher in eyes with PDR ((2143.7 +/- 1685.21) pg/ml) than in eyes with IMH ((142.42 +/- 72.83) pg/ml, P < 0.001). The vitreous level of SDF-1 was also significantly higher in eyes with PDR ((306.37 +/- 134.25) pg/ml) than in eyes with IMH ((86.91 +/- 55.05) pg/ml, P < 0.001). The concentrations of both VEGF and SDF-1 were higher in eyes with active PDR than in eyes with inactive PDR. Panretinal photocoagulation (PRP) could decrease the SDF-1 levels in the vitreous of PDR patients. The vitreous concentration of SDF-1 correlated with that of VEGF in eyes with PDR (r = 0.61, P < 0.001). The costaining of SDF-1 and VEGF was confined to the vascular components in preretinal membranes. CONCLUSIONS: SDF-1 protein is highly expressed in both the vitreous and preretinal membranes of PDR patients; SDF-1 may be correlated with VEGF in angiogenesis in PDR.

No association between polymorphism of serotonin transporter gene and depression in Parkinson's disease in Chinese.

Depressive symptoms affect 40% to 50% of Parkinson's disease (PD) patients, and adversely impact their quality of life. The decrease of serotonin (5-HT) in the synaptic cleft is commonly considered as the cause of depression. The reuptake of 5-HT released into the synaptic cleft is mediated by the 5-HT transporter (5-HTT). Many studies have focused on the relationship between the 5-HTT-linked polymorphic region (5-HTTLPR) and depression. The present study is to investigate the association between the polymorphisms in the promoter of the 5-HTT gene (including 5-HTTLPR and rs25531), which determine either a higher or lower 5-HT uptake, and risk for depression of PD. Three hundred six idiopathic PD patients were recruited randomly from hospital clinic and the Center for Epidemiological Studies Depression Scale (CES-D) was used as the diagnosis or rating scale for depression. Polymerase Chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used and the patients' genotypes were divided as L(A), L(G), S(A), and S(G). We found no evidence for an association between variants of 5-HTTLPR and rs25531 alleles, and depressive symptoms in Chinese PD patients.

Caspase-dependent retinal ganglion cell apoptosis in the rat model of acute diabetes.

BACKGROUND: Neural apoptosis is generally believed to be mediated by two distinct pathways, caspase-dependant and caspase-independent pathways. This study investigated the apoptotic pathways involved in retinal ganglion cells in acute diabetes in rats. METHODS: Diabetes was induced in male Wistar rats by a peritoneal injection of streptozotocin (STZ). Expression and localization of caspase-3 and apoptosis-inducing factor (AIF) proteins in the retina of diabetic rats was examined by Western blotting and immunohistochemistry analyses. Terminal transferase dUTP nick end labeling (TUNEL) assay and immunofluorescent staining specific for caspase-3 and AIF were applied to analyze for apoptosis of retinal ganglion cells. In addition, a caspase-3 inhibitor DEVD-CHO was injected intravitreally to further determine the apoptotic pathways of retinal ganglion cells triggered in acute diabetes. RESULTS: Two weeks after induction of diabetes, a significant increase in caspase-3 protein expression and localization occurred in the nerve fiber layer, ganglion cell layer, and inner plexiform layer of the retina. Four weeks after the onset of diabetes, the increase in caspase-3 expression was profound eight weeks postinduction of diabetes (P < 0.05). Meanwhile, no AIF protein expression was detected in this study. In addition, intravitreal administration of the caspase-3 inhibitor DEVD-CHO reduced apoptosis of retinal ganglion cells by its direct inhibitory action on caspase-3. CONCLUSION: Caspase-dependent apoptotic pathways may be the main stimulant of STZ-induced retinal ganglion cell apoptosis in acute diabetes.