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Introduction and Aims: The histological and morphological differences in soft tissue between natural teeth and peri-implant may result in different clinical effectiveness to free gingival graft (FGG). This research aims to investigate the different efficacy of FGG in augmenting keratinized tissue width (KTW) between tooth and implant sites while evaluating its medium-term stability over a 2- to 5-year follow-up., Methods: In this study, 29 patients underwent FGG to address insufficient clinical scenarios when KTW <2 mm at the buccal aspect, including 37 implant sites and 33 natural teeth sites both in posterior regions were included. The KTW and gingival margin position (GMP) of these sites was assessed by measuring the intra-oral photographs which were taken at 0 days (T0), 3-month (T1), 6-month (T2), 12-month post-surgery (T3), and 2 to 5 years follow-up (T4)., Results: The results revealed that KTW increased significantly in both groups. However, the natural teeth group showed significantly less graft shrinkage (GS) than the implants group. (Teeth: 2.05 ± 0.51 mm and 25.42% ± 6.45%; Implants: 3.18 ± 0.65 mm and 38.92% ± 5.39%, P <.01). From T1 to T4. The gingival margin coronally advanced by 0.47 ± 0.51 mm and 0.18 ± 0.43 mm for the natural teeth and implants group, respectively (P<.05)., Conclusions: A greater KTW reduction after FGG was observed at implants versus natural teeth. And, the graft surrounding implants after crown restoration was stable for up to 2 to 5 years., Clinical Relevance: By comparing the changes in KTW around natural teeth and implants following FGG to investigate whether there are differences between them and the degree of differences. Additionally, this allows us to explore whether the restorations impact the effect of FGG. This research can assist clinicians in selecting an appropriate amount of soft tissue during surgery to achieve treatment goals, reduce postoperative discomfort for patients, and enhance predictability in clinicians' ability to increase keratinized tissue. Furthermore, by observing changes in the position of GMP around natural teeth and implants, the effectiveness of FGG in root coverage can be understood, thus improving the predictability of FGG for root coverage., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making., Methods: D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn's test or the Bonferroni test for pairwise comparisons., Results: A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p < 0.001) compared to the control group., Conclusion: GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery., (© 2024. The Author(s).)

Abstract: Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs. In the present study, we used the patch-clamp technique to record GABA subtype A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in RGCs from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic mIPSCs in RGCs without altering their amplitude, suggesting a reduction in the spontaneous release of GABA to RGCs. Topical administration of GLP-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of RGCs. Concurrently, the protective effects of GLP-1 on RGCs in diabetic rats were eliminated by topical administration of exendin-9-39, a specific GLP-1 receptor antagonist, or SR95531, a specific antagonist of the GABA subtype A receptor. Furthermore, extracellular perfusion of GLP-1 was found to elevate the frequencies of GABAergic mIPSCs in both ON- and OFF-type RGCs. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of GLP-1 receptor activation. Moreover, multielectrode array recordings revealed that GLP-1 functionally augmented the photoresponses of ON-type RGCs. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of GLP-1. These results suggest that GLP-1 facilitates the release of GABA onto RGCs through the activation of GLP-1 receptor, leading to the de-excitation of RGC circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the GABA system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of GLP-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

Chronic myeloid leukaemia (CML) is caused by BCR::ABL1. Tyrosine kinase-inhibitors (TKIs) are the initial therapy. Several organizations have reported milestones to evaluate response to initial TKI-therapy and suggest when a change of TKI should be considered. Achieving treatment-free remission (TFR) is increasingly recognized as the optimal therapy goal. Which TKI is the best initial therapy for which persons and what depth and duration of molecular remission is needed to achieve TFR are controversial. In this review we discuss these issues and suggest future research directions., Competing Interests: Declaration of competing Interest RPG is a consultant to Antengene Biotech LLC, Ascentage Pharma Group and NexImmune Inc.; Medical Director, FFF Enterprises Inc.; Board of Directors: Russian Foundation for Cancer Research Support; and Scientific Advisory Boards, Nanexa AB and StemRad Ltd. Fig. 2 and Fig. 3–4 were created with BioRender and Figdraw, respectively., (Copyright © 2023. Published by Elsevier Ltd.)

Developing efficient integrated diagnosis and treatment agents based on fuel-free self-movement nanomotors remains challenging in antitumor therapy. In this study, a covalent organic framework (COF)-based biomimetic nanomotor composed of polypyrrole (PPy) core, porphyrin-COF shell, and HCT116 cancer cell membrane coating is reported. Under near-infrared (NIR) light irradiation, the obtained mPPy@COF-Por can overcome Brownian motion and achieves directional motion through self-thermophoretic force generated from the PPy core. The HCT116 cancer cell membrane coating enables the nanomotor to selectively recognize the source cell lines and reduces the bio-adhesion of mPPy@COF-Por in a biological medium, endowing with this NIR light-powered nanomotor good mobility. More importantly, such multifunctional integration allows the COF-based nanomotor to be a powerful nanoagent for cancer treatment, and the high infrared thermal imaging/photoacoustic imaging/fluorescence trimodal imaging-guided combined photothermal/photodynamic therapeutic effect on HCT116 tumor cell is successfully achieved. The results offer considerable promise for the development of COF nanomotors with integrated imaging/therapy modalities in biomedical applications., (© 2023 Wiley-VCH GmbH.)

Objective: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients., Methods: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro ., Results: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets ( r =0.49), the absolute reticulocyte count ( r =0.45), and the percentage of neutrophils ( r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes ( r =-0.45). The expressions of CD25 and CD69 in both CD4 + and CD8 + T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4 + and CD8 + T cells from AA patients were markedly suppressed ( P =0.01 and P < 0.01)., Conclusion: The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro .

Progressive damage of retinal ganglion cells (RGCs) is observed in early diabetic retinopathy. Intracellular Ca 2+ overload mediated by Ca 2+ influx through voltage-gated Ca 2+ channels (VGCCs) is involved in neurodegeneration, whereas glucagon-like peptide-1 (GLP-1) provides neuroprotection. However, whether GLP-1 plays a neuroprotective role in diabetic retinas by modulating VGCCs remains unknown. We found that eye drops of exendin-4, a long-acting GLP-1 receptor (GLP-1R) agonist, prevented the increase of L-type Ca 2+ current ( I LCa ) densities of RGCs induced by 4-week hyperglycemia and promoted RGC survival by suppressing L-type VGCC (L-VGCC) activity in streptozotocin-induced diabetic rats. Moreover, exendin-4-induced suppression of I LCa in RGCs may be mediated by a GLP-1R/Gs/cAMP-PKA/ryanodine/Ca 2+ /calmodulin/calcineurin/PP1 signaling pathway. Furthermore, exendin-4 functionally improved the light-evoked spiking ability of diabetic RGCs. These results suggest that GLP-1R activation enhances cAMP to PP1 signaling and that PP1 inactivates L-VGCCs by dephosphorylating them, thereby reducing Ca 2+ influx, which could protect RGCs against excitotoxic Ca 2+ overload., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Light modulates mood through various retina-brain pathways. We showed that mice treated with short-term acute bright light exposure displayed anxiety-related phenotypes in a prolonged manner even after the termination of the exposure. Such a postexposure anxiogenic effect depended upon melanopsin-based intrinsically photosensitive retinal ganglion cell (ipRGC) activities rather than rod/cone photoreceptor inputs. Chemogenetic manipulation of specific central nuclei demonstrated that the ipRGC-central amygdala (CeA) visual circuit played a key role in this effect. The corticosterone system was likely to be involved in this effect, as evidenced by enhanced expression of the glucocorticoid receptor (GR) protein in the CeA and the bed nucleus of the stria terminalis and by the absence of this effect in animals treated with the GR antagonist. Together, our findings reveal a non-image forming visual circuit specifically designed for "the delayed" extinction of anxiety against potential threats, thus conferring a survival advantage.

Metal nanoclusters (NCs) have been unleashed as an emerging category of metal materials by virtue of integrated merits including the unusual atom-stacking mode, quantum confinement effect, and fruitful catalytically active sites. Nonetheless, development of metal NCs as photosensitizers is blocked by light-induced instability and ultrashort carrier lifespan, which remarkably retards the design of metal NC-involved photosystems, hence resulting in the decreased photoactivities. To solve these obstacles, herein, we conceptually probed the charge transfer characteristics of the BiVO 4 photoanode photosensitized by atomically precise alloy metal NCs, wherein tailor-made l-glutathione-capped gold-silver bimetallic (AuAg) NCs were controllably self-assembled on the BiVO 4 substrate. It was uncovered that alien Ag atom doping is able to effectively stabilize the alloy AuAg NCs and simultaneously photosensitize the BiVO 4 photoanode, significantly boosting the photoelectrochemical (PEC) water oxidation performances. The reasons for the robust and stable PEC water oxidation activities of the AuAg NCs/BiVO 4 composite photoanode were unambiguously unleashed. We ascertain that Ag atom doping in the staple motif of Au x NCs efficaciously protects the NCs from rapid oxidation, enhancing the photostability, boosting the photosensitization efficiency, and thus leading to the considerably improved PEC water splitting activities compared with the homometallic counterpart. This work could afford a new strategy to judiciously tackle the inherent detrimental instability of metal NCs for solar energy conversion.

Objective: To explore the difference of lymphocyte subsets in peripheral blood (PB) between aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS) patients, meanwhile to compare the clinical parameters obtained from PB and bone marrow (BM)., Methods: The lymphocyte subsets in hypo-MDS ( n =25) and AA ( n =33) patients were investigated by flow cytometry. Meanwhile, the differences in PB cell counts, biochemical indicators, BM cell counts and abnormal chromosomes between the two groups were analyzed., Results: The percentage of CD8 + T cells in AA group was significantly higher than that in hypo-MDS group ( P =0.001), while the percentage of CD4 + T cells and the CD4 + /CD8 + ratio in AA group were obviously lower than those in hypo-MDS group ( P =0.015 and 0.001, respectively). Furthermore, the proportion of CD4 + and CD8 + activated T (TA) cells, and memory Tregs in AA group was distinctly lower than those in hypo-MDS group ( P =0.043, 0.015 and 0.024, respectively). Nevertheless, the percentage of CD8 + naive T (TN) cells in AA patients was remarkably higher ( P =0.044). And hypo-MDS patients had declined lymphocyte counts ( P =0.025), increased levels of total bilirubin (TBil), lactate dehydrogenase (LDH), vitamin B12 and proportion of BM blasts than AA patients ( P =0.019, 0.023, 0.027 and 0.045, respectively)., Conclusion: In this study it was confirmed that the percentages of CD4 + and CD8 + TA cells, memory Tregs and CD8 + TN cells were significantly different between AA and hypo-MDS patients, which provide an essential basis for the identification of these two diseases.

Objective: This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM)., Methods: Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1β) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM., Results: The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1β in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1β as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1β rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1β blockade using neutralizing IL-1β monoclonal antibody or siRNA of IL-1β suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1β and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum., Conclusion: NLRP3/caspase-1/IL-1β axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM., (© 2022. The Author(s).)

This study aimed to investigate the prevalence and diversity of extended-spectrum β-lactamases (ESBL)-producing Escherichia coli isolates from healthy individuals in a community and to elucidate their dissemination mechanism. Cefotaxime-resistant E. coli were isolated from 95 samples of healthy persons from one community in Yangzhou, China, and were tested for minimal inhibitory concentrations of 14 antimicrobial agents. The isolates were subjected to whole genome sequencing by Illumina Hiseq or PacBio single-molecule real-time sequencing. A total of 30 cefotaxime-resistant E. coli isolates were obtained, carrying bla CTX-M (n=29) or bla DHA (n=1), of which the bla CTX-M-55 (n=19) was the most predominant genotype. One novel bla CTX-M variant bla CTX-M-252 was identified. Thirteen CTX-M-55-producing E. coli isolates belonged to ST8369 from nasal (n=12) or faecal (n=1) samples shared the identical cgMLST type, resistance profiles, resistance genes, plasmid replicons, and a 5,053-bp bla CTX-M-55 structure ΔIS 26 -ΔIS Ecp1 - bla CTX-M-55 -Δ orf477 -ΔTn 2 . The bla CTX-M-55 gene was located on IncHI2/ST3 plasmid in E. coli ST8369. The lengths of bla CTX-M / bla DHA -carrying contigs in the remaining 17 E. coli strains ranged from 1,663 to 382,836 bp, located on chromosome (n=4) or plasmids (n=5); the location of the other eight contigs could not be determined due to incomplete assembly. The bla CTX-M was associated with IS Ecp1 as previously reported. Nasal colonization of CTX-M-55-producing ST8369 E. coli strains has occurred among healthy individuals in one community. There is a potential risk of antimicrobial resistance dissemination between humans within one community through close contact or environment via aerosols or dust. Therefore, surveillance of nasal carriage of bla CTX-M in communities is warranted to further monitor the spread of the antimicrobial resistance genes in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Jiang, Shao, Lu, Lu, Jiao, Li and Wang.)

Objective: At present, the longest network transmission distance (NTD) for 5G remote endoscopic surgery is reportedly only about 229 km, and the NTD longer than 5 000 km has not yet been reported in clinical application. In this study, we attempted the clinical application of 5G ultra-remote robot-assisted laparoscopic surgery in spermatic vein ligation., Methods: This retrospective study included two cases of 5G ultra-remote robot-assisted laparoscopic spermatic vein ligation using the home-made Tumai Surgical Robot System. The operation table was located in Xinjiang Kezhou People's Hospital, with an NTD of about 5 800 km (a linear distance of about 3 800 km) from the surgeon's console in the Telemedical Center of the First Affiliated Hospital of Nanjing Medical University, the apparatuses connected through the public 5G network. We observed the network connection delay, network fluctuation, and data packet loss rate of the devices at both ends of the loop through the feedback value of the Ping command by real-time monitoring., Results: The total operation time of the two cases was 45 and 40 minutes respectively, with a mean blood loss of < 5 ml. The patients resumed a liquid diet and out-of-bed activity on the first day, the abdominal drainage tubes removed on the second, and both discharged from the hospital on the third day. The intraoperative average two-way network delay was 130 ms, and the average continuous data packet loss rate was 1.4%. No adverse network events, such as network interruption, occurred during the operation., Conclusion: Through the public 5G network and home-made Tumai Surgical Robot System, ultra-remote robot-assisted laparoscopic surgery was performed safely and successfully.

Dissecting neural connectivity patterns within local brain regions is an essential step to understanding the function of the brain. 1 Neural microcircuits in brain regions, such as the neocortex and the hippocampus, have been extensively studied. 2 By contrast, the microcircuit in the hypothalamus remains largely uncharacterized. The hypothalamus is crucial for animals' survival and reproduction. 3 Knowledge of how different hypothalamic nuclei coordinate with each other and outside brain regions for hypothalamus-related functions has been significantly advanced. 4-9 Although there are limited studies on the neural microcircuit in the lateral hypothalamus (LHA) 10 , 11 and the suprachiasmatic nucleus (SCN), 12 , 13 the patterns of neural microcircuits in most of the given hypothalamic nuclei remain largely unknown. This study applied combinatory approaches to address the local neural circuit pattern in the ventromedial hypothalamus (VMH) and other hypothalamic nuclei. We discovered a unique neural circuit design in the VMH. Neurons in the VMH were electrically coupled at the early postnatal stage like ones in the neocortex. 14 However, unlike neocortical neurons, 14 , 15 they developed very few chemical synapses after the disappearance of electrical synapses. Instead, VMH neurons communicated with neuropeptides. The similar scarceness of synaptic connectivity found in other hypothalamic nuclei further indicated that the lack of synaptic connections is a unique feature for local neural circuits in most adult hypothalamic nuclei. Thus, our findings provide a solid synaptic basis at the cellular level to understand hypothalamic functions better., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Previous studies have shown the essential role of inflammation in rapid eye movement (REM) sleep behavior disorder (RBD). However, the association of RBD in Parkinson's disease (PD) with peripheral blood inflammatory cytokines is still unknown. We investigated the relationship between inflammatory cytokines and the clinical characteristics of PD patients with RBD., Methods: A total of 153 PD patients and 36 healthy controls were included in this study, and blood plasma was collected. PD patients were classified as PD with RBD (PD-RBD, n = 60) and PD without RBD (PD-nRBD, n = 93). Inflammatory factor levels were compared among the control, PD-RBD, and PD-nRBD groups., Results: The PD-RBD group had significantly higher C-reactive protein (CRP) levels (P < 0.001), monocytes (P = 0.003), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001), whereas this group has lower lymphocytes levels (P < 0.001) and lymphocyte-to-monocyte ratio (LMR) (P < 0.001) than the PD-nRBD group. Univariate and multivariate logistic regression analysis indicated that LMR (P < 0.0001 odds ratio [OR] = 0.424) was a protective factor, whereas CRP (P < 0.001 OR = 2.326) was a risk factor for the PD-RBD group. PD-RBD patients had lower Montreal Cognitive Assessment (Beijing version) (MoCA) (P < 0.001) and Mini-Mental State Examination (MMSE) (P = 0.039) scores than PD-nRBD patients., Conclusions: Significant differences were found in inflammation levels between PD-RBD and PD-nRBD, suggesting that inflammatory factors are associated with the pathogenesis of RBD in PD patients. Thus, CRP and LMR levels may serve as biomarkers and predict the prognosis of PD patients with RBD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The increasing global prevalence of myopia calls for elaboration of the pathogenesis of this disease. Here, we show that selective ablation and activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in developing mice induced myopic and hyperopic refractive shifts by modulating the corneal radius of curvature (CRC) and axial length (AL) in an opposite way. Melanopsin- and rod/cone-driven signals of ipRGCs were found to influence refractive development by affecting the AL and CRC, respectively. The role of ipRGCs in myopia progression is evidenced by attenuated form-deprivation myopia magnitudes in ipRGC-ablated and melanopsin-deficient animals and by enhanced melanopsin expression/photoresponses in form-deprived eyes. Cell subtype-specific ablation showed that M1 subtype cells, and probably M2/M3 subtype cells, are involved in ocular development. Thus, ipRGCs contribute substantially to mouse eye growth and myopia development, which may inspire novel strategies for myopia intervention.

Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (G s ) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca 2+ ] i of GCs through the IP 3 -sensitive pathway and was blocked in Ca 2+ -free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct G s /cAMP-PKA/IP 3 /Ca 2+ /CaM/CaMKII signaling pathway, following the activation of GLP-1Rs., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

External light-independent antitumor PDT is successfully realized with a covalent organic framework (COF)-based host-guest nanosystem. Its highly effective antitumor behavior is fully demonstrated by both H 2 O 2 -overexpressed 4T1 and H 2 O 2 -less expressed HCT116 and MCF-7 xenograft models.

Objective: To investigate the value of contrast-enhanced ultrasound (CEUS) for the diagnosis of cervical tuberculous lymphadenitis (CTL)., Methods: The cohort study included 203 consecutive patients diagnosed with cervical lymph node. Before pathological or laboratory confirmation, all patients underwent CEUS examination, and the imaging findings were analyzed afterward. The diagnostic efficiency of the CEUS imaging findings of CTL was evaluated., Results: Nighty-seven patients of the 203 (47.8%) were pathologically or laboratory confirmed with a CTL diagnosis while the remainder (52.2%) were diagnosed with non-tuberculous lymphadenitis. Regarding the imaging findings of CEUS, it was more common in CTL patients to find a pattern of heterogeneous enhancement inside the lymph nodes relative to non-tuberculous patients [81.44% (79/97) vs 15.09% (16/106), P < 0.01]. The sensitivity of the feature in diagnosis for CTL was 81.44% and the specificity was 84.91%, resepectively. Furthermore, a pattern of peripheral rim-like enhancement had been notable in CTL patients compared with non-tuberculous patients [86.60% (84/97) vs 12.26% (13/106), P < 0.01], associating with a diagnostic sensitivity of 86.60% and a specificity of 87.74%. When it came to the combination of both imaging findings mentioned above, the features were more prominent in CTL patients than compared with non-tuberculous patients [74.23% (72/97) vs 5.66% (6/106), P < 0.01], with a diagnostic sensitivity of 74.23% and a high specificity of 94.34%. Regarding area under curve (AUC) for the ROC analysis, the feature of internal heterogeneous enhancement, peripheral rim-like enhancement, and both features were 0.832, 0.872, and 0.843., Conclusions: CEUS patterns of heterogeneous enhancement and peripheral rim-like enhancement of lymph nodes are helpful characteristics for the diagnosis of CTL.

Background: Orthostatic hypotension (OH) is a common nonmotor symptom in patients with Parkinson's disease (PD), with an incidence ranging from 14% to 54%., Aims: This study explored changes in cognition and transcranial sonography (TCS) findings in patients with PD and OH., Methods: We enrolled PD patients who visited the outpatient or inpatient department from 2017 to 2020. Blood pressure was measured in different positions, and demographic data were collected. Motor and nonmotor symptoms were evaluated using standard scales. A subset of 107 patients underwent TCS., Results: We enrolled 66 PD-OH patients and 92 PD-no orthostatic hypotension (NOH) patients. There were no significant differences in gender, age, disease duration, or Hoehn and Yahr stage between groups. Binary logistic regression revealed age as an independent risk factor for OH in PD patients. There were statistically significant group differences in visuospatial and executive function and Unified Parkinson's Disease Rating Scale (UPDRS) I and II scores (p < .05). Among PD-OH patients, there was a statistically significant difference in UPDRS II and III scores between patients with or without clinical symptoms (p < .05). The substantia nigra (SN) area was significantly larger in PD-NOH patients (0.45 ± 0.18 cm 2 ) than PD-OH patients (0.34 ± 0.16 cm 2 ) (p < .05)., Conclusions: PD-OH patients had poorer visuospatial and executive function and lower UPDRS I and II scores compared with PD-NOH patients. Within the PD-OH group, there was no significant difference in cognition between patients with or without clinical symptoms. The difference in the SN area may indicate different subtypes of PD or a tendency to develop parkinsonism syndrome., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

We show for the first time that the neuropeptide orexin modulates pupillary light response, a non-image-forming visual function, in mice of either sex. Intravitreal injection of the orexin receptor (OXR) antagonist TCS1102 and orexin-A reduced and enhanced pupillary constriction in response to light, respectively. Orexin-A activated OX 1 Rs on M2-type intrinsically photosensitive retinal ganglion cells (M2 cells), and caused membrane depolarization of these cells by modulating inward rectifier potassium channels and nonselective cation channels, thus resulting in an increase in intrinsic excitability. The increased intrinsic excitability could account for the orexin-A-evoked increase in spontaneous discharges and light-induced spiking rates of M2 cells, leading to an intensification of pupillary constriction. Orexin-A did not alter the light response of M1 cells, which could be because of no or weak expression of OX 1 Rs on them, as revealed by RNAscope in situ hybridization. In sum, orexin-A is likely to decrease the pupil size of mice by influencing M2 cells, thereby improving visual performance in awake mice via enhancing the focal depth of the eye's refractive system. SIGNIFICANCE STATEMENT This study reveals the role of the neuropeptide orexin in mouse pupillary light response, a non-image-forming visual function. Intravitreal orexin-A administration intensifies light-induced pupillary constriction via increasing the excitability of M2 intrinsically photosensitive retinal ganglion cells by activating the orexin receptor subtype OX 1 R. Modulation of inward rectifier potassium channels and nonselective cation channels were both involved in the ionic mechanisms underlying such intensification. Orexin could improve visual performance in awake mice by reducing the pupil size and thereby enhancing the focal depth of the eye's refractive system., (Copyright © 2021 the authors.)

To explore the individual effect and interaction of diabetes and family history and other risk factors on hypertension in Han in Shanghai China. The method of case-control study with l:l matched pairs was used, 342 cases of hypertension and 342 controls were selected and investigate their exposed factors with face-to-face. The method of epidemiology research was used to explore the individual effect and interaction of diabetes and family history and other risk factors on hypertension. The individual effect of family history (OR = 4.103, 95%CI 2.660-6.330), diabetes (OR = 4.219, 95%CI 2.926-6.083), personal taste (OR = 1.256, 95%CI 1.091-1.593), drinking behavior (OR = 1.391, 95%CI 1.010-1.914) and smoking behavior (OR = 1.057, 95%CI 1.00-1.117) were significant (p < 0.05). But individual effect of sex, education, occupation, work/life pressure, environmental noise, sleeping time and sports habit were not significant (p > 0.05). The OR of interaction between FH and DM to hypertension was 16.537 (95%CI 10.070-21.157), between FH and drinking behavior was 4.0 (95%CI 2.461-6.502), FH and sport habit was 7.668 (95%CI 3.598-16.344), FH and personal taste was 6.521 (95%CI 3.858-11.024), FH and smoking behavior was 5.526 (95%CI 3.404-8.972), FH and work/life pressure was 4.087 (95%CI 2.144-7.788). The SI of FH and DM was 2.27, RERI was 8.68, AP was 52.48% and PAP was 55.86%. FH and DM, personal taste, smoking behavior had positive interaction on hypertension, but FH and sport habits, drinking behavior, work/life pressure had reverse interaction on hypertension. FH and diabetes were very important risk factors with significant effect for hypertension. FH and diabetes, personal taste, smoking behavior had positive interaction on hypertension, but FH and sport habits, drinking behavior, work/life pressure had reverse interaction on hypertension.

Objective: To investigate the diagnostic value of core-needle biopsy (CNB) guided by contrast-enhanced ultrasound (CEUS) in cervical tuberculous lymphadenitis (CTL)., Methods: 178 patients with pathological confirmation of CTL were retrospectively enrolled. All of them had undergone CNB prior to the final surgery. According to the different ways of puncture guidance, they were divided into two groups: conventional ultrasound (US) group (n = 81) and CEUS group (n = 97). The comparison of diagnostic efficacy between two groups was compared and analyzed., Results: Among the 178 patients, 146 were directly diagnosed as CTL by CNB, including 59 patients in CEUS group and 87 patients in US group. The diagnostic accuracy were 89.7% (87/97) and 72.8% (59/81), respectively (P < 0.01). For subgroup analyses, differences among diagnostic efficacy ascribed to the different guiding methods were significant in medium size group (>2.0 cm and ≤3.0 cm) and large size group (>3.0 cm), 91.7% for CEUS group vs. 69.0% for US group (P < 0.05) and 84.4% for CEUS group vs. 57.7% for US group (P < 0.05), respectively., Conclusions: In the diagnosis of CTL, compared with the US-guided CNB, CEUS-guided CNB have certain advantages, especially for larger lymph nodes.

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z =3.48, P =0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] ( P =0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients ( P =0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients ( P =0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS ( r (s)=0.109, P =0.125; r (s)=-0.022, P =0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients ( P =0.016, P =0.046, P =0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% ( P =0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference ( z =0.83, P =0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

Background: BMI is an indicator commonly used in the world to measure the weight and height of the body, it reflects the comprehensive outcome of acquired lifestyle; FH is a sign reflecting the main role of genetic factors. This study aimed to evaluate the effect of BMI and interaction with FH on hypertension risk in Shanghai adult population., Methods: According to l:l matched pairs design, 342 cases and 342 controls were selected and investigated in this study, this study was performed in Shanghai, China. Participants received face-to-face questionnaire survey, anthropometric tests and laboratory examinations. Relevant indicators that reflect obesity including BMI and waist to hip ratio (WHR) were calculated. Multivariate logistic regression analysis was applied to explore the association between factors and hypertension risk. Interactive effect was evaluated by synergy index (SI), relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and the percentage of the interaction between the pure factors (PAP)., Results: Among 684 study participants aged 28-87 years old, the differences of mean age and height between case group and control group are no significant ( p  > 0.05), but the differences of mean of weight, WC, HC, BMI and WHR are significant ( p  < 0.001). The OR of FH on hypertension is 4.986 (95%CI: 2.832~ 8.877); the OR of BMI on hypertension is respectively: low weight is 1.528 (95%CI: 0.551~ 4.239), overweight is 3.333 (95%CI: 1.678~ 6.617) and obesity is 7.312 (95%CI: 3.556~ 15.035). The OR of interaction between FH and BMI to hypertension is 12.993 (95%CI: 7.426~22.734). SI is 1.90 (95% CI: 1.48~3.78), RERI is 5.67 (95% CI: 1.66~11.88), AP is 43.87% (95% CI: 12.84~91.88%), and PAP is 47.55% (95%CI: 13.91~99.58%). FH and BMI have positive interaction on hypertension. 43.87% of hypertension exposed to both FH and BMI was attributable to the interaction of them., Conclusions: FH and BMI are significant higher risks of hypertension; with the increase of BMI, the risk of hypertension will increase more. FH and BMI have positive interaction with hypertension, the interaction is greater than the sum of two independent actions., Competing Interests: Ethical approval was granted by Jiading district center for disease control and prevention research ethics committee. All subjects gave verbal and written informed consent to participate in the study, they would like to participate in investigation and answer all the related questions in the questionnaire. The survey was conducted by a full-time investigator using a questionnaire and face-to-face inquiries.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: To assess the prevalence and related factors of benign paroxysmal positional vertigo (BPPV) in patients with spontaneous intracranial hypotension (SIH)., Methods: We retrospectively reviewed 156 consecutive inpatients with SIH, and collected the clinical and radiological data. These patients were divided into BPPV group and non-BPPV group according to the clinical manifestation and the results of Dix-Hallpike or supine roll tests during hospitalization period. We performed a univariate analysis and a further multiple logistic regression analysis to identify the related factors of the development of BPPV in SIH patients., Results: BPPV was detected in 18 patients among the total 156 SIH patients (11.54%). The univariate analysis showed a low cerebrospinal fluid (CSF) pressure (P = 0.018), a small pontomesencephalic angle (P = 0.012) and a positive venous distension sign (VDS) (P = 0.045) were associated with the presence of BPPV. But the multivariate analysis only demonstrated a low CSF pressure was related to the presence of BPPV (OR = 1.022, 95% CI: 1.001-1.043, P = 0.044)., Conclusion: BPPV is common in SIH patients. SIH patients with low CSF pressure may be prone to develop BPPV.

Objective: To determine the valuable hemolytic characteristics in differential diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA) and hereditary spherocytosis (HS). Method: The clinical and hemolytic characteristics of 108 PNH patients, 127 AIHA patients and 172 HS patients diagnosed from January 1998 to April 2017 were compared. Results: ①Reticulocyte percentage (Ret%) of PNH patients [6.70% (0.14%-22.82%)] was significantly lower than that of AIHA [14.00%(0.10%-55.95%), P <0.001] and HS patients [11.83%(0.60%-57.39%), P <0.001]. The Ret% in PNH patients were significantly lower than those in AIHA and HS patients at the same levels of anemia, except for in mild anemia between PNH and AIHA patients. However, when comparing the Ret% between AIHA and HS patients, there was significant difference only in mild anemia [7.63%(1.87%-29.20%)% vs 11.20%(3.31%-22.44%), z =-2.165, P =0.030]. ②The level of TBIL in HS patients was significantly higher than that in AIHA and PNH patients [79.3 (11.2-244.0) μmol/L vs 57.6 (7.6-265.0) μmol/L, z =5.469, P <0.001; 79.3(11.2-244.0) μmol/L vs 26.2(4.6-217.7) μmol/L, z =-2.165, P <0.001], and the proportion of HS patients with TBIL more than 4 times the upper limit of normal (ULN) (64.1%) was significantly higher than that of AIHA (37.7%, χ (2)=19.896, P <0.001) and PNH patients (4.6%, P <0.001). ③The LDH level of PNH patients was significantly higher than that of AIHA and HS [1 500 (216-5 144) U/L vs 487 (29-3 516) U/L, z =-9.556, P <0.001; 1 500 (216-5 144) U/L vs 252 (132-663) U/L, z =-11.518, P <0.001], and the proportion of PNH patients with LDH more than 1 000 U/L (79.1%) was significantly higher than that of AIHA patients (13.0%, χ (2)=93.748, P <0.001) and HS patients (0, P <0.001). ④Splenomegaly occurred in 43.5% of PNH patients, including 16.0% with severe splenomegaly. In contrast, the occurrence of splenomegaly was 98.6% in AIHA patients and 100.0% in HS patients ( P <0.001), and 63.0% of AIHA patients ( P <0.001) and 90.4% of HS patients ( P <0.001) were with severe splenomegaly. ⑤The prevalence of cholelithiasis in HS patients was up to 43.1%, significantly higher than that in AIHA patients (10.5%, P <0.001) and PNH patients (2.9%, P <0.001). Conclusion: The comprehensive assessment of the five hemolytic characteristics is simplified, practical and efficient, with great clinical significance, providing specific indicators for differential diagnosis and efficient approach for making further work-up.

Objective: To detect the expression of miRNA in de novo and complete response SAA patients and predict the targets of the miRNAs., Methods: The expression profiles of miRNA from bone marrow mononuclear cells of the SAA patients with de novo and CR were detected by miRNA microarray., Results: Totally 35 up-regulated and 37 down-regulated miRNA were identified in CR SAA patients in comparison with de novo SAA patients. Furthermore, by predicting the targets of the differentlly expressed miRNA, it was found that some targets associated with T cell receptor signaling pathway and cell adhesion molecules., Conclusion: Some miRNA may be involved in the pathogenesis of SAA.

Objective: To explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA)., Methods: the clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed., Results: HAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19 + B cells proportion (P=0.046) and more obvious imbalance of CD4 + /CD8 + ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001)., Conclusion: HAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.

The specific mechanisms for epigenetic regulation of gene transcription remain to be elucidated. We previously demonstrated that hyperacetylation of histone H3K9 in promoter II of glioma cells promotes high transcription of the glial cell line-derived neurotrophic factor (GDNF) gene. This hyperacetylation significantly enhanced Egr-1 binding and increased the recruitment of RNA polymerase II (RNA POL II) to that region (P < 0.05). Egr-1 expression was abnormally increased in C6 glioma cells. Further overexpression of Egr-1 significantly increased Egr-1 binding to GDNF promoter II, while increasing RNA POL II recruitment, thus increasing GDNF transcription (P < 0.01). When the acetylation of H3K9 in the Egr-1 binding site was significantly reduced by the histone acetyltransferase (HAT) inhibitor curcumin, binding of Egr-1 to GDNF promoter II, RNA POL II recruitment, and GDNF mRNA expression were significantly downregulated (P < 0.01). Moreover, curcumin attenuated the effects of Egr-1 overexpression on Egr-1 binding, RNA POL II recruitment, and GDNF transcription (P < 0.01). Egr-1 and RNA POL II co-existed in the nucleus of C6 glioma cells, with overlapping regions, but they were not bound to each other. In conclusion, highly expressed Egr-1 may be involved in the recruitment of RNA POL II in GDNF promoter II in a non-binding manner, and thereby involved in regulating GDNF transcription in high-grade glioma cells. This regulation is dependent on histone hyperacetylation in GDNF promoter II.

Objective: To investigate the clinical characteristics and gene mutations of patients with Gilbert syndrome complicated with myeloproliferative neoplasms (MPN)., Methods: Peripheral blood samples from 1 patient with Gilbert syndrome complicated with MPN and his son were collected to analyse all exon mutations of UGT1A1 gene., Results: The patient with leukocytosis, thrombocythemia, mild anemia and positive JAK2/V617F mutation was initially diagnosed as MPN. The hyperbilirubinemia suggested concurrent disease. Further gene evaluation disclosed a insertion mutation in the (TA) 6 TAA box, and a missense mutation(G→A) at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating enzyme uridine-diphosphoglucuronosyl transferase1A1 (UGT1A1). His son only carried some polymorphism mutation without manifestation of this disease., Conclusion: It is a first report case of MPN complicated with Gilbert syndrome that can highlight the differential diagnosis for hyperbilirubinemia.

Objective: To assess the clinical feature and outcomes of severe aplastic anemia (SAA) patients suffered from bacteremia following antithymocyte globulin (ATG). Methods: A total of 264 cases hospitalized in our hospital between Jan 2000 and July 2011 were enrolled into this study. We evaluated the associated pathogens of bacteremia, analyzed the risk factors by Logistic regression and estimated the overall survival (OS) by Kaplan-Meier method for the cohort of patients. Results: Bloodstream infections occurred in 49 patients, with a median age of 20 (4-62) years, including 38 cases with very SAA (VSAA) and 11 SAA patients. The median time of bacteremia was 13 (2-233) days following ATG administration. The most common microbiologically were Enterobacteriaceae (28.4% ), Pseudomonas aeruginosa (20.9% ) and Klebsiella pneumonia (14.9% ). Almost half (46.9% ) of these bacteria were resistant to most or all available antibacterial classes. Univariate and multivariate analyses demonstrated that VSAA, infections during previous week before ATG treatment were risk factors for bacteremia. The 3 and 6 months response rates (10.6% and 17.0% ) were poor in the patients with bloodstream infections, which were significantly lower than those patients without infections (35.6% and 55.6%, respectively, both P <0.001). The estimated 5-year OS were 36.4% (95% CI 21.3% to 51.5%) and 74.5% (95% CI 68.4% to 80.7%) in the two groups, respectively ( P <0.001). Conclusions: ①VSAA has higher risk of bacteremia than SAA; ②Infections during previous week before ATG administration was a risk factor for bacteremia; ③ The outcomes of SAA or VSAA patients suffered from bacteremia following ATG was poor.

Background: Recent studies applied laser-evoked potentials (LEP) for the analysis of small nerve fibre function and focused on the detection of stable C-fibre-mediated potentials (C-LEPs); high technical requirements were needed. The diagnostic significance is still controversially discussed. So far, only few studies focused on the susceptibility of C-LEPs to distraction and other influences. We hypothesized that C-LEPs are altered by habituation processes and distraction., Methods: Twelve subjects were tested with a C-fibre laser set-up (neodymium:yttrium-aluminium-perovskite laser with a 10-mm beam diameter and 10-ms stimulus time) at the left perioral area. In condition I, the subjects received repetitive painful laser stimuli at the right hand to induce habituation. In condition II, the subjects had to fulfil an auditory discrimination task (where the subjects had to estimate the pitch of different tones on a scale for 20 min). C-LEPs were retrieved before and after the habituation or distraction paradigm. C-LEPs were also measured in a control group who was not influenced by laser stimuli or other disturbances during a 23-min break between the two test sessions., Results: In both test conditions, there was significant C-LEP amplitude reduction. The LEP amplitudes of the control group remained unchanged., Conclusions: In the approach of detecting C-fibre-mediated potentials with LEP, future studies should take the high susceptibility to distraction and habituation into account., (© 2015 European Pain Federation - EFIC®)

Objective: To explore the clinical features of autoimmune hemolytic anemia (AIHA) with monoclonal gammopathy IgMκ., Methods: The clinical and laboratory features of 12 AIHA with monoclonal gammopathy IgMκ were retrospectively analyzed., Results: 12 cases with monoclonal immunoglobulin IgMκ were found in 85 patients with AIHA by immune-fixation electrophoresis from June 2012 to June 2014. There were 4 (5.7% ) cases of warm AIHA and 8 (80.0% ) cases of cold agglutinin syndrome (CAS). The 4 warm AIHA were primary type, and 4 CAS cases were secondary to lymphoproliferative disorder (small-cell lymphocytic lymphoma) and the other 4 CAS were primary type. Positive TCR gene rearrangements were detected in 2 warm AIHA patients; IgH rearrangements positive were detected in 6 CAS patients, and TCR/IgH rearrangements positive were seen in 1 CAS patient. Four warm AIHA cases received glucocorticoid treatment, three cases of complete remission, one case of partial response. Three CAS cases were treated with low-dose of rituximab, two cases of partial response and one case of invalid. Two CAS patients received chemotherapy of COP regimen, one case of partial response and one case of invalid. Two CAS patients of normal hemoglobin were suggested to keep warm, and one case died of infection after splenectomy., Conclusions: Mostly, CAS patients had monoclonal immunoglobulin IgMκ, but warm AIHA patients with monoclonal IgM were fewer.

Objective: Laser-evoked potential (LEP) habituation was investigated under the influence of capsaicin-induced peripheral and central sensitization., Material and Methods: Fifteen subjects received 100 repetitive painful laser stimuli at the right hand dorsum at primary (application area; condition I) and secondary areas (beyond application area; condition II) in two different sessions after applying capsaicin topically. Conditions I and II were compared to a control condition without capsaicin application. N1, N2, and P2 latencies and N1 and N2/P2 amplitudes were recorded by EEG. Quantitative sensory testing (QST) and the Liewald Diary reaction time experiment were used as control tests., Results: QST documented heat hyperalgesia as a sign of peripheral sensitization in the primary area and pinprick hyperalgesia in the primary and secondary area as a sign of central sensitization, after applying capsaicin. The N2/P2 amplitude habituation was significantly reduced in the primary area compared to controls (the primary area represents peripheral sensitization). The LEPs of the secondary area (the secondary area represents central sensitization) showed no significant N2/P2 amplitude habituation compared to controls. The comparison between conditions I vs. II showed no significant difference regarding N2/P2 amplitude and laser pain rating., Conclusion: Capsaicin-induced central sensitization does not alter LEP habituation. The physiological habituation of LEP amplitudes is reduced due to peripheral mechanisms after applying capsaicin topically. These findings form a basis for future studies, which use the habituation paradigm to investigate pain conditions promoted by sensitization phenomena., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

A total of 258 malaria cases with 2 deaths were reported during 2007-2014, including 148 vivax malaria cases, 106 falciparum malaria cases, and 4 ovale malaria cases. During 2007-2009, 86.0% (135/157) were vivax malaria cases with 3 indigenous cases. In 2010-2014, the proportion of falciparum malaria is increasing year by year, and all were imported cases. 98.8% were imported from Africa and other provinces in China. Most cases occurred among patients aged 20-49 years, and the male-to-female ratio was 3.16:1. Most patients were workers and commercial service personnel. The malaria epidemic situation is relatively stable in Wenzhou. Malaria control and elimination interventions should emphasize the monitoring and education of transient population to control the imported cases, and explore multi-sector coordination for malaria prevention and control.

Objective: To investigate the clinical characteristics of Chinese patients with paroxysmal nocturnal hemoglobinuria (PNH)., Methods: The clinical data of 70 adult PNH cases in our hospital from January 2000 to December 2009 were analyzed retrospectively, and the clinical manifestation, laboratory examination, treatment, complications and prognostic factors influencing survival rate were assessed., Results: The nosopoietic median age of 70 cases(41 male cases and 29 female cases) was 37 (18-73) years old. The clinical manifestation included fatigue (87.1%), hemogolobinuria (44.3%), infection (22.9%), bleeding (37.1%), and abdominal pain (2.9%). FHb (free hemoglobin) in 56 patients (80%) was <50 mg/L. Hp (haptoglobin) in 54 patients (77.1%) was <0.5 g/L, and LDH in 49 patients (70.0%) was <220 U/L. The overall 10 year-survival rate after diagnosis was 72.2% estimated by Kaplan-Meier. The complications in this study were as follow: recurrent abdominal pain crisis (2.9%), infections (30.0%), thrombotic events (8.6%), evolution to MDS/AML (5.7%), calculus (11.4%) and death (17.1%). Both univariate and multivariate analyses identified risk factors affecting survival, including development of thrombotic events, progression to myelodysplastic syndrome or acute myelogenous leukemia (MDS/AML) and recurrent infections., Conclusion: This larger number of cases for the first time allowed us to carry out a detailed analysis of prognostic factors for this rare disease. Evaluation of PNH prognostic factors may provide a basis to assess the current and future therapies of this disease.

Objective: To survey the features and its impact of neuropathic pain in neurological outpatients., Methods: A total of 106 patients with neuropathic pain were selected from Neurology Clinic of the Second Affiliated Hospital of Zhejiang University. General status instrument, SF-36 Quality of Life Scale and Hamilton Anxiety Scale (HAMA) were used in the survey., Results: Trigeminal neuralgia (23.6%), nerve root pain (21.7%), and post-herpetic neuralgia (13.2%) were the most common causes of neuropathic pain. The sequence of impairments in life quality of the patients was role-physical (21.2), bodily pain (39.9), role-emotional (41.2), general health (50.0), physical functioning (55.1), vitality (60.0), mental health (68.5), and social functioning (70.9). Pearson correlation coefficients were statistically significant between bodily pain and other dimensions of life quality (P<0.05). Western medication (45.3%) was the most common treatment adopted by physicians., Conclusion: The prevalence of neuropathic pain is common in elderly patients. The three major types of neuropathic pain seriously affect the quality of life in patients. Although western medicine is the first choice of treatment, clinical drug selection should be standardized with efforts of both doctors and patients.

Background: Autosomal-dominant polycystic kidney disease (ADPKD) is the most common form of cystic kidney disease. The mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling but plays an uncertain role in the treatment of ADPKD. The objective of our study was to conduct a meta-analysis of randomized controlled trials (RCTs) to present an objective appraisal of the efficacy and safety of sirolimus therapy in patients with ADPKD., Methods: We conducted a meta-analysis of RCTs performed in adults with ADPKD, and compared the effect of sirolimus on total kidney volume (TKV), glomerular filtration rate (GFR), cyst volume, and daily urinary protein excretion. Safety was evaluated based on analysis of blood pressure, lipid profile, complete blood count, infection, and other reported adverse events., Results: Four RCTs were included. The sirolimus therapy group had smaller TKV than the control group. The mean difference (MD) of TKV post-treatment compared with the control group was -234.74 (P = .01). However, GFR did not reach a statistically significant difference between groups. Standard mean difference (SMD) of GFR after therapy was 0.24 (95% confidence interval [CI], 0.05-0.52; P = .11), but sirolimus seemed to increase urine protein excretion (P = .002). There was no statically significant difference in leukocytes, hemoglobin, platelets, and blood pressure between groups. Aphthous stomatits and pharyngitis are reported more commonly in the sirolimus therapy group compared with the control group (P < .000001)., Conclusions: In ADPKD patients, treatment with sirolimus is safe and can effectively slow kidney growth, but it seems not to slow down the decrease of GFR., (Copyright © 2014 Elsevier Inc. All rights reserved.)