HMGB1 released from nociceptors mediates inflammation.

Inflammation, the body's primary defensive response system to injury and infection, is triggered by molecular signatures of microbes and tissue injury. These molecules also stimulate specialized sensory neurons, termed nociceptors. Activation of nociceptors mediates inflammation through antidromic release of neuropeptides into infected or injured tissue, producing neurogenic inflammation. Because HMGB1 is an important inflammatory mediator that is synthesized by neurons, we reasoned nociceptor release of HMGB1 might be a component of the neuroinflammatory response. In support of this possibility, we show here that transgenic nociceptors expressing channelrhodopsin-2 (ChR2) directly release HMGB1 in response to light stimulation. Additionally, HMGB1 expression in neurons was silenced by crossing synapsin-Cre (Syn-Cre) mice with floxed HMGB1 mice (HMGB1f/f). When these mice undergo sciatic nerve injury to activate neurogenic inflammation, they are protected from the development of cutaneous inflammation and allodynia as compared to wild-type controls. Syn-Cre/HMGB1fl/fl mice subjected to experimental collagen antibody-induced arthritis, a disease model in which nociceptor-dependent inflammation plays a significant pathological role, are protected from the development of allodynia and joint inflammation. Thus, nociceptor HMGB1 is required to mediate pain and inflammation during sciatic nerve injury and collagen antibody-induced arthritis.

RASSF1A inhibits epithelial-mesenchymal transition of gastric cancer cells by downregulating P-JNK.

Gastric cancer (GC) is one of the most common gastrointestinal tumors. In this study, we assessed the biological role of Ras association domain family 1 isoform A (RASSF1A) in GC cells. Expressions of RASSF1A and the relationship of RASSF1A with epithelial-mesenchymal transformation (EMT)-related proteins were assessed in five cell lines using Western blot. GC cells with RASSF1A overexpression were used to study sensitivity to cisplatin, migration, invasion, and the expression of EMT-associated biomarkers. GC cells showed profound downregulation of RASSF1A expression compared with normal human gastric mucosal cells. High RASSF1A expression was associated with increased overall survival. Overexpression of RASSF1A regulates GC cells activity and the expression of EMT-associated biomarkers. RASSF1A regulates E-cadherin and Vimentin through P-JNK pathway. Our results revealed that RASSF1A can inhibit the proliferation, migration, and invasion of GC cells via E-cadherin. Our study provides insights for further research on GC.

One-pot synthesis of AuAgPd trimetallic nanoparticles with peroxidase-like activity for colorimetric assays.

In this work, AuAgPd trimetallic nanoparticles (AuAgPd TNPs) with intrinsic and broad-spectrum peroxidase-like activity were synthesized through a one-pot method by co-reduction of HAuCl4, AgNO3, and Na2PdCl4 with NaBH4. The morphology and composition of AuAgPd TNPs were characterized. The peroxidase-like activity of AuAgPd TNPs were highly dependent on the composition and nanostructure of AuAgPd TNPs. Rationally designed AuAgPd TNPs could catalyze the oxidation of various chromogenic substrates including 3,3'5,5'-tetramethylbenzidine (TMB), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and o-phenylenediamine (OPD) by H2O2 to generate blue, green, and yellow products, respectively. Kinetic assays indicated that AuAgPd TNPs exhibited high affinity to H2O2. Then, sensitive colorimetric assays were developed for H2O2 detection by using ABTS, OPD, and TMB as chromogenic substrates, respectively. Lowest limit of detection (LOD) of 3.1 µM with wide linear range of 6-250 µM was obtained by using ABTS as substrate. Hydrogen sulfide ion (HS-) could effectively inhibit the peroxidase-like activity of AuAgPd TNPs. Thus, a selective colorimetric assay was further fabricated for HS- detection with LOD of 2.3 µM. This work provides an effective way for the synthesis of trimetallic nanozyme with peroxidase-like activity and also for tailoring their catalytic activity for desired use. Graphical abstract.

Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3/GSDME activation.

Gasdermin E (GSDME) has an important role in inducing secondary necrosis/pyroptosis. Upon apoptotic stimulation, it can be cleaved by activated caspase-3 to generate its N-terminal fragment (GSDME-NT), which executes pyroptosis by perforating the plasma membrane. GSDME is expressed in many human lung cancers including A549 cells. Paclitaxel and cisplatin are two representative chemotherapeutic agents for lung cancers, which induce apoptosis via different action mechanisms. However, it remains unclear whether they can induce GSDME-mediated secondary necrosis/pyroptosis in lung A549 cancer cells. Here we showed that both paclitaxel and cisplatin evidently induced apoptosis in A549 cells as revealed by the activation of multiple apoptotic markers. Notably, some of the dying cells displayed characteristic morphology of secondary necrosis/pyroptosis, by blowing large bubbles from the cellular membrane accompanied by caspase-3 activation and GSDME-NT generation. But the ability of cisplatin to induce this phenomenon was much stronger than that of paclitaxel. Consistent with this, cisplatin triggered much higher activation of caspase-3 and generation of GSDME-NT than paclitaxel, suggesting that the levels of secondary necrosis/pyroptosis correlated with the levels of active caspase-3 and GSDME-NT. Supporting this, caspase-3 specific inhibitor (Ac-DEVD-CHO) suppressed cisplatin-induced GSDME-NT generation and concurrently reduced the secondary necrosis/pyroptosis. Besides, GSDME knockdown significantly inhibited cisplatin- but not paclitaxel-induced secondary necrosis/pyroptosis. These results indicated that cisplatin induced higher levels of secondary necrosis/pyroptosis in A549 cells than paclitaxel, suggesting that cisplatin may provide additional advantages in the treatment of lung cancers with high levels of GSDME expression.

ATP induces caspase-3/gasdermin E-mediated pyroptosis in NLRP3 pathway-blocked murine macrophages.

ATP acts as a canonical activator to induce NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome activation in macrophages, leading to caspase-1/gasdermin D (GSDMD)-mediated pyroptosis. It remains unclear whether ATP can induce pyroptosis in macrophages when the NLRP3 pathway is blocked by pathogenic infection. In this study, we used cellular models to mimic such blockade of NLRP3 activation: bone marrow-derived macrophages (BMDMs) treated with NLRP3-specific inhibitor MCC950 and RAW264.7 cells deficient in ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression. The results showed that ATP treatment induced lytic cell death morphologically resembling canonical pyroptosis in both MCC950-treated BMDMs and RAW264.7 cells, but did not cause the activation of caspase-1 (by detecting caspase-1p10 and mature interleukin-1ß) and cleavage of GSDMD. Instead, both apoptotic initiator (caspase-8 and -9) and executioner (caspase-3 and -7) caspases were evidently activated and gasdermin E (GSDME) was cleaved to generate its N-terminal fragment (GSDME-NT) which executes pyroptosis. The GSDME-NT production and lytic cell death induced by ATP were diminished by caspase-3 inhibitor. In BMDMs without MCC950 treatment, ATP induced the formation of ASC specks which were co-localized with caspase-8; with MCC950 treatment, however, ATP did not induced the formation of ASC specks. In RAW264.7 cells, knockdown of GSDME by small interfering RNA attenuated ATP-induced lytic cell death and HMGB1 release into culture supernatants. Collectively, our results indicate that ATP induces pyroptosis in macrophages through the caspase-3/GSDME axis when the canonical NLRP3 pathway is blocked, suggestive of an alternative mechanism for combating against pathogen evasion.

Inhibition of HMGB1/RAGE-mediated endocytosis by HMGB1 antagonist box A, anti-HMGB1 antibodies, and cholinergic agonists suppresses inflammation.

BACKGROUND: Extracellular high mobility group box 1 protein  (HMGB1) serves a central role in inflammation as a transporter protein, which binds other immune-activating molecules that are endocytosed via the receptor for advanced glycation end-products (RAGE). These pro-inflammatory complexes are targeted to the endolysosomal compartment, where HMGB1 permeabilizes the lysosomes. This enables HMGB1-partner molecules to avoid degradation, to leak into the cytosol, and to reach cognate immune-activating sensors. Lipopolysaccharide (LPS) requires this pathway to generate pyroptosis by accessing its key cytosolic receptors, murine caspase 11, or the human caspases 4 and 5. This lytic, pro-inflammatory cell death plays a fundamental pathogenic role in gram-negative sepsis. The aim of the study was to identify molecules inhibiting HMGB1 or HMGB1/LPS cellular internalization. METHODS: Endocytosis was studied in cultured macrophages using Alexa Fluor-labeled HMGB1 or complexes of HMGB1 and Alexa Fluor-labeled LPS in the presence of an anti-HMGB1 monoclonal antibody (mAb), recombinant HMGB1 box A protein, acetylcholine, the nicotinic acetylcholine receptor subtype alpha 7 (α7 nAChR) agonist GTS-21, or a dynamin-specific inhibitor of endocytosis. Images were obtained by fluorescence microscopy and quantified by the ImageJ processing program (NIH). Data were analyzed using student's t test or one-way ANOVA followed by the least significant difference or Tukey's tests. RESULTS: Anti-HMGB1 mAb, recombinant HMGB1 antagonist box A protein, acetylcholine, GTS-21, and the dynamin-specific inhibitor of endocytosis inhibited internalization of HMGB1 or HMGB1-LPS complexes in cultured macrophages. These agents prevented macrophage activation in response to HMGB1 and/or HMGB1-LPS complexes. CONCLUSION: These results demonstrate that therapies based on HMGB1 antagonists and the cholinergic anti-inflammatory pathway share a previously unrecognized molecular mechanism of substantial clinical relevance.

Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction.

BACKGROUND: The aim of this study was to explore the possible correlations of serum cystatin C level and cystatin C gene (CST3) polymorphism with vascular cognitive impairment in patients who had acute cerebral infarction. METHODS: A total of 152 patients with acute cerebral infarction were recruited in this case-control study. Patients were divided into vascular cognitive impairment (VCI) group (n = 71) and cognitive impairment no dementia (CIND) group (n = 81). The serum concentrations of cystatin C were measured with immunoturbidimetric assay while the gene polymorphisms of CST3 were determined by technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In the VCI group, serum cystatin C level was significantly higher than that in the control group. The frequency of the B allele was found to be higher in the VCI group as compared with that of the CIND group (18.5% vs 7.7%, p = 0.006). In logistic regression analysis, significant associations of VCI with high serum cystatin C level (OR 3.837 (1.176-12.520), p = 0.026) and CST3 B allele (OR 2.038 (1.048-3.963), p = 0.036) were also found. CONCLUSIONS: A high cystatin C level and CST3 B allele confer risks for VCI after acute cerebral infarction. It is probable that measurement of the serum cystatin C level and detection of CST3 gene polymorphism would aid in the early diagnosis of VCI, but further studies are warranted.

Quick and selective extraction of Z-ligustilide from Angelica sinensis using magnetic multiwalled carbon nanotubes.

A facile and highly efficient magnetic solid-phase extraction method has been developed for Z-ligustilide, the major therapeutic agent in Angelica sinensis. The solid-phase adsorbent material used was prepared by conjugating carbon nanotubes with magnetic Fe3 O4 nanoparticles via a hydrothermal reaction. The magnetic material showed a high affinity toward Z-ligustilide due to the π-π stacking interaction between the carbon nanotubes and Z-ligustilide, allowing a quick and selective exaction of Z-ligustilide from complex sample matrices. Factors influencing the magnetic solid-phase extraction such as the amount of the added adsorbent, adsorption and desorption time, and desorption solvent, were investigated. Due to its high extraction efficiency, this method was proved highly useful for sample cleanup/enrichment in quantitative high-performance liquid chromatography analysis. The proposed method had a linear calibration curve (R(2) = 0.9983) over the concentration between 4 ng/mL and 200 µg/mL Z-ligustilide. The accuracy of the method was determined by the recovery, which was from 92.07 to 104.02%, with the relative standard deviations >4.51%.

Initial experience of correlating parameters of intravoxel incoherent motion and dynamic contrast-enhanced magnetic resonance imaging at 3.0 T in nasopharyngeal carcinoma.

PURPOSE: To determine the correlation between intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters. METHODS: Thirty-eight newly diagnosed NPC patients were prospectively enrolled. Diffusion-weighted images (DWI) at 13 b-values were acquired using a 3.0-T MRI system. IVIM parameters including the pure molecular diffusion (D), perfusion-related diffusion (D*), perfusion fraction (f), DCE-MRI parameters including maximum slope of increase (MSI), enhancement amplitude (EA) and enhancement ratio (ER) were calculated by two investigators independently. Intra- and interobserver agreement were evaluated using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Relationships between IVIM and DCE-MRI parameters were evaluated by calculation of Spearman's correlation coefficient. RESULTS: Intra- and interobserver reproducibility were excellent to relatively good (ICC = 0.887-0.997; narrow width of 95 % limits of agreement). The highest correlation was observed between f and EA (r = 0.633, P < 0.001), with a strong correlation between f and MSI (r = 0.598, P = 0.001). No correlation was observed between f and ER (r = -0.162; P = 0.421) or D* and DCE parameters (r = 0.125-0.307; P > 0.119). CONCLUSION: This study suggests IVIM perfusion imaging using 3.0-T MRI is feasible in NPC, and f correlates significantly with EA and MSI. KEY POINTS: Assessment of tumour perfusion is important in nasopharyngeal carcinoma. DCE-MRI provided perfusion information with the use of intravenous contrast media. Perfusion information could be provided by non-invasive IVIM MRI. IVIM parameter f correlated with DCE-MRI parameters.

Body composition and metabolic syndrome in patients with type 1 diabetes.

BACKGROUND: In recent years, the prevalence of obesity and metabolic syndrome in type 1 diabetes (T1DM) patients has gradually increased. Insulin resistance in T1DM deserves attention. It is necessary to clarify the relationship between body composition, metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention. AIM: To assess body composition (BC) in T1DM patients and evaluate the relationship between BC, metabolic syndrome (MS), and insulin resistance in these indi-viduals. METHODS: A total of 101 subjects with T1DM, aged 10 years or older, and with a disease duration of over 1 year were included. Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters. Clinical and laboratory data were collected, and insulin resistance was calculated using the estimated glucose disposal rate (eGDR). RESULTS: MS was diagnosed in 16/101 patients (15.84%), overweight in 16/101 patients (15.84%), obesity in 4/101 (3.96%), hypertension in 34/101 (33.66%%) and dyslipidemia in 16/101 patients (15.84%). Visceral fat index (VFI) and trunk fat mass were significantly and negatively correlated with eGDR (both P < 0.001). Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients. Binary logistic regression analysis revealed that significant factors for MS included eGDR [P = 0.017, odds ratio (OR) = 0.109], VFI (P = 0.030, OR = 3.529), and a family history of diabetes (P = 0.004, OR = 0.228). Significant factors for hypertension included eGDR (P < 0.001, OR = 0.488) and skeletal muscle mass (P = 0.003, OR = 1.111). Significant factors for dyslipidemia included trunk fat mass (P = 0.033, OR = 1.202) and eGDR (P = 0.037, OR = 0.708). CONCLUSION: Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM. BC analysis, specifically identifying visceral fat (trunk fat), may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.

Remote ischemic conditioning in the treatment of acute cerebral infarction: A case control study.

Objective: This paired case-control study aimed to evaluate the efficacy and safety of remote ischemic conditioning (RIC) in patients with acute cerebral infarction (CI) and explore potential serological markers of RIC. Methods: Patients with acute CI (<72 h) were matched 1:1 according to age, sex, and CI conditions and were divided into the RIC group and the control group. The RIC group received RIC intervention for 7 days on top of routine treatment, while the control group received a sham RIC. The curative effects and adverse reactions were observed. Result: A total of 66 patients (mean age 60.00 ± 11.37 years; mean time of acute CI onset 32.91 ± 17.94 h) completed the study. The National Institute of Health stroke scale score on day 7, modified Rankin Scale scores on day 7 and day 90 were significantly lower than the baseline in the RIC group (P < 0.001, P = 0.003, P = 0.004, respectively) but not in the control group (P = 0.056, P = 0.169, P = 0.058, respectively). RIC was well-tolerated, and no adverse events were reported. Both plasma hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor increased in the RIC group from day 0 to day 7, while they decreased in the control group. The changes in plasma HIF-1α in the RIC group were statistically different from those in the control group (P = 0.006). Conclusion: Early and short-term RIC treatment was well-tolerated and effective in improving the prognosis in acute CI. HIF-1α can be recognized as a biomarker for evaluating the efficacy of RIC treatment.

Total structure and optical properties of a phosphine/thiolate-protected Au24 nanocluster.

We report the synthesis and total structure determination of a Au(24) nanocluster protected by mixed ligands of phosphine and thiolate. Single crystal X-ray crystallography and electrospray ionization mass spectrometry (ESI-MS) unequivocally determined the cluster formula to be [Au(24)(PPh(3))(10)(SC(2)H(4)Ph)(5)X(2)](+), where X = Cl and/or Br. The structure consists of two incomplete (i.e., one vertex missing) icosahedral Au(12) units joined by five thiolate linkages. This structure shows interesting differences from the previously reported vertex-sharing biicosahedral [Au(25)(PPh(3))(10)(SC(2)H(4)Ph)(5)X(2)](2+) nanocluster protected by the same type and number of phosphine and thiolate ligands. The optical absorption spectrum of Au(24) nanocluster was theoretically reproduced and interpreted.

A comparison of the ultrastructure and composition of fruits' cuticular wax from the wild-type 'Newhall' navel orange (Citrus sinensis [L.] Osbeck cv. Newhall) and its glossy mutant.

KEY MESSAGE: The altered ultrastructure and composition of cuticular wax from 'glossy Newhall' (MT) fruits lead to its glossy phenotype. A novel mutant derived from the wild-type (WT) 'Newhall' navel orange (Citrus sinensis [L.] Osbeck cv. Newhall), named 'glossy Newhall' (MT), which produced much more glossy fruits that were easily distinguishable from the WT fruits was characterized in this report. The total wax loads of both WT and MT fruits varied considerably during the fruit development. The most abundant wax fraction of WT mature fruits was triterpenoids, followed by aldehydes, alkanes, fatty acids, primary alcohol and cholesterol. The total wax load in MT mature fruits was reduced by 44.2 % compared with WT. Except for the minor wax components of primary alcohol and cholesterol, the amounts of all major wax fractions in MT mature fruits were decreased in varying degrees. The major reduction occurred in aldehydes that decreased 96.4 % and alkanes that decreased 81.9 %, which was consistent with scanning electron micrographs of MT mature fruit surfaces that showed a severe loss of wax crystals. Hence, aldehydes and alkanes were suggested to be required for wax crystal formation in 'Newhall' navel orange fruits.

Dys-psychological Stress Effect on Expressions of P53 and NFκBp65 in Human Ovarian Carcinoma In Vivo.

OBJECTIVE: To investigate the dys-psychological stress effect on the growth of subcutaneous xenotransplanted tumor in nude mice bearing human epithelium ovarian carcinoma, and the influence on P53 and NFκBp65 expressions. METHODS: The subcutaneous tumor xenografts were established by implanting human epithelium ovarian carcinoma tissues into nude mice and the dys-psychological stress model was established with restraint. The mice were randomized into the following four treatment groups with each group six mice respectively: tumor group (group A), normal saline intraperitoneal injection; tumor with stress group (group B), normal saline intraperitoneal injection; tumor therapy group (group C), cisplatin intraperitoneal injection; and tumor therapy with stress group (group D), cisplatin intraperitoneal injection. The expressions of P53 and NFκBp65 in tumor tissues were determined by Western blotting. RESULTS: The expressions of P53 and NFκBp65 in each restraint group were enhanced compared with the control groups (P<0.05). CONCLUSION: The dys-psychological stress may induce the high expressions of P53 and NFκBp65 proteins and further promote tumor growth.

Data-Driven Colormap Adjustment for Exploring Spatial Variations in Scalar Fields.

Colormapping is an effective and popular visualization technique for analyzing patterns in scalar fields. Scientists usually adjust a default colormap to show hidden patterns by shifting the colors in a trial-and-error process. To improve efficiency, efforts have been made to automate the colormap adjustment process based on data properties (e.g., statistical data value or histogram distribution). However, as the data properties have no direct correlation to the spatial variations, previous methods may be insufficient to reveal the dynamic range of spatial variations hidden in the data. To address the above issues, we conduct a pilot analysis with domain experts and summarize three requirements for the colormap adjustment process. Based on the requirements, we formulate colormap adjustment as an objective function, composed of a boundary term and a fidelity term, which is flexible enough to support interactive functionalities. We compare our approach with alternative methods under a quantitative measure and a qualitative user study (25 participants), based on a set of data with broad distribution diversity. We further evaluate our approach via three case studies with six domain experts. Our method is not necessarily more optimal than alternative methods of revealing patterns, but rather is an additional color adjustment option for exploring data with a dynamic range of spatial variations.

The application of sudoscan for screening microvascular complications in patients with type 2 diabetes.

The aim of the study was to evaluate the performance of sudoscan in screening diabetic microvascular complications in patients with type 2 diabete mellitus (T2DM). 515 patients with T2DM aged from 23 to 89 years were included for analysis in our study. The mean age was 60.00 ± 11.37 years and the mean duration of T2DM was 8.44 ± 7.56 years. Electrochemical skin conductance (ESC) in hands and feet was evaluated by SUDOCAN. Diabetic peripheral neuropathy (DPN) was diagnosed in 378 patients (44.3%), diabetic kidney disease (DKD) in 161 patients (31.26%), diabetic retinopathy (DR) in 148 patients (28.74%). Hands and feet ESC was significantly and independently associated with the presence of DPN, DKD and DR. Patients with a lower ESC (<60 µS) had 5.63-fold increased likelihood of having DPN, 4.90-fold increased likelihood of having DKD, 1.01-fold increased likelihood of having DR, than those with a higher ESC. Age, duration of T2DM, smoking, renal function and vibration perception thresholds were negatively correlated with ESC. Sudoscan parameters were correlated with diabetic microvascular complications, especially with DPN. Sudoscan could be an effective screening tool in primary health care for early screening microvascular complications.

A dual tracer [11C]PBR28 and [18F]FDG microPET evaluation of neuroinflammation and brain energy metabolism in murine endotoxemia.

BACKGROUND: Brain metabolic alterations and neuroinflammation have been reported in several peripheral inflammatory conditions and present significant potential for targeting with new diagnostic approaches and treatments. However, non-invasive evaluation of these alterations remains a challenge. METHODS: Here, we studied the utility of a micro positron emission tomography (microPET) dual tracer ([11C]PBR28 - for microglial activation and [18F]FDG for energy metabolism) approach to assess brain dysfunction, including neuroinflammation in murine endotoxemia. MicroPET imaging data were subjected to advanced conjunction and individual analyses, followed by post-hoc analysis. RESULTS: There were significant increases in [11C]PBR28 and [18F]FDG uptake in the hippocampus of C57BL/6 J mice 6 h following LPS (2 mg/kg) intraperitoneal (i.p.) administration compared with saline administration. These results confirmed previous postmortem observations. In addition, patterns of significant simultaneous activation were demonstrated in the hippocampus, the thalamus, and the hypothalamus in parallel with other tracer-specific and region-specific alterations. These changes were observed in the presence of robust systemic inflammatory responses manifested by significantly increased serum cytokine levels. CONCLUSIONS: Together, these findings demonstrate the applicability of [11C]PBR28 - [18F]FDG dual tracer microPET imaging for assessing neuroinflammation and brain metabolic alterations in conditions "classically" characterized by peripheral inflammatory and metabolic pathogenesis.

Residual ß-Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study.

OBJECTIVE: To investigate the natural history and related factors of the pancreatic ß-cell function in Chinese type 1 diabetic patients from 3C study Shantou center. METHOD: Stimulated C-peptide levels from follow-up data of 201 individuals in 3C study Shantou subgroup starting in 2012 were used. Residual ß-cell function was defined as stimulated C - peptide level ≥ 0.2 pmol/mL, on the basis of cut-points derived from the Diabetes Control and Complications Trial (DCCT). RESULTS: 36.8% of patients had residual ß-cell function, and the percentage was 68.2% in newly diagnosed diabetic patients. COX regression analysis indicated that the age of diagnosis, HbA1C level, and duration were independent factors of residual ß-cell function in individuals with ≤5 years duration, but in those with duration ≥5 years, only the age of diagnosis was a predictor. The pancreatic ß-cell function mainly declined in the first 5 years of the duration, and the rate of decline was correlated negatively with the duration and age of diagnosis. Receiver operating characteristic (ROC) analysis indicated that the cut-off point of stimulated C-peptide was 0.615 pmol/mL in patients with <5 years duration to have 7% HbA1c. CONCLUSION: Age at diagnosis was the strongest predictor for residual C-peptide. There was a more rapid decline of stimulated C-peptide in duration ≤5 years and younger patients. Therefore, intervention therapies of ß-cells should start from the early stage, and the recommended target goal of stimulated C-peptide is 0.615 pmol/mL or above.

Corrigendum to "Residual ß-Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study".

[This corrects the article DOI: 10.1155/2021/9946874.].

Prevalence and Related Factors of Depression, Anxiety, Acute Stress, and Insomnia Symptoms Among Medical Staffs Experiencing the Second Wave of COVID-19 Pandemic in Xinjiang, China.

The prevalence and related factors of mental health impact among medical staffs who experienced the second wave of the COVID-19 pandemic in China is unknown. Therefore, this survey was conducted to investigate the prevalence and related factors of depressive, anxiety, acute stress, and insomnia symptoms in medical staffs in Kashi, Xinjiang, China during the second wave of the COVID-19 pandemic. A cross-sectional online survey was conducted among medical staffs working in First People's Hospital of Kashi, Xinjiang. The questionnaire collected demographic data and self-design questions related to the COVID-19 pandemic. The Impact of Events Scale-6, the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder Scale-7, the Perceived Social Support Scale, the Chinese Big Five Personality Inventory-15, and the Trait Coping Style Questionnaire were used to measure psychological symptoms or characteristics. Binary logistic regression was carried out to examine the associations between socio-demographic factors and symptoms of depression, anxiety, stress, and insomnia. In total, data from 123 participants were finally included, among which the prevalence rate of depressive, anxiety, acute stress, and insomnia symptoms is 60.2, 49.6, 43.1, and 41.1%, respectively. The regression model revealed that minority ethnicity, being worried about infection, spending more time on following pandemic information, and neurotic personality were positively associated with the mental health symptoms, while extraversion personality, higher education level, and better social support were negatively associated. In our study, the prevalence of mental health impact was high among medical staffs in Kashi, China who experienced the second wave of the COVID-19 pandemic. Several factors were found to be associated with mental health conditions. These findings could help identify medical staffs at risk for mental health problems and be helpful for making precise mental health intervention policies during the resurgence. Our study may pave way for more research into Xinjiang during the COVID-19 pandemic.