Neuregulin4-ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.

AIM: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)-neuregulin 4 (NRG4)-ErbB4 axis, with somatotopic dependence. MATERIALS AND METHODS: We established a high-fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c-Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B-NRG4-ErbB4 axis was verified by peripheral specific antagonism of ErbB4. RESULTS: ES at the forelimb and abdomen regions significantly up-regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD-induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. CONCLUSION: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4-ErbB4 signaling pathway.

Consensus for antifungal stewardship in China (2024 edition).

Background: Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods: Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results: Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions: This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.

Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

PURPOSE: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. METHODS: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. RESULTS: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. CONCLUSIONS: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.

The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination.

NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.

Sex differences in the association between sleep duration and muscle quality index in adults: A cross-sectional study from NHANES 2011-2014.

OBJECTIVE: The aim of this study was to investigate the association between sleep duration and muscle quality index (MQI) in middle-aged and older age groups, as limited evidence exists on this topic. METHODS: In order to assess the relationship between sleep duration and MQI, a cross-sectional study was undertaken, utilizing data from the National Health and Nutrition Examination Survey (NHANES) acquired during the period from 2011 to 2014. The study comprised a total of 4598 participants aged 20 years and above. To examine the association between sleep duration and MQI, sophisticated weighted multivariate linear regression models were employed. Additionally, smooth curve fitting techniques were applied to examine the possibility of any non-linear relationship between the two variables. RESULTS: The average age of the adults who were enrolled in the study was 38.48±11.69 years, and 46.75% of them were female. The results of the multivariable linear regression models showed that sleep duration had a positive correlation with MQI. However, when subgroup analysis was conducted, it was found that this positive correlation only existed among women (ß = 0.09, 95% CI: 0.014 to 0.167). To further confirm the differences between sexes in the relationship between sleep duration and MQI, a weighted generalized additive model (GAM) was used. CONCLUSIONS: This research study provides evidence that there is a positive correlation between the duration of sleep and MQI specifically in females, while no such association was observed in males. These findings shed light on the existence of gender disparities in the connection between sleep duration and MQI.

Compact high-power 320-nm continuous-wave single-frequency laser based on power scaling of a diode-pumped Pr:LiYF4 ring laser at red.

Single-frequency (SF) lasers in the visible spectral region are usually obtained through an indirect method, i.e., frequency doubling of near-infrared SF lasers. In this work, we report on the direct generation of a high-power continuous-wave (CW) SF laser in red based on a diode-pumped Pr:LiYF4 (YLF) ring cavity technology. A maximum output power is scaled to 3.98 W at 640 nm with a linewidth of about 17.2 MHz and a power stability of 0.6%. Moreover, by inserting a LBO crystal into the ring cavity for intracavity frequency doubling of the 640 nm SF laser, we have also successfully demonstrated an ultraviolet (UV) SF laser at 320 nm, for the first time to the best of our knowledge, with a maximum power of 670 mW. This work provides a promising route for the development of simple, compact, and high-power SF lasers operating in visible and UV spectral regions.

Experimental Study on the Detection of the Existence and Location of Mimicked and Unexpected Interface Debonding Defects in an Existing Rectangular CFST Column with PZT Materials.

Interface bonding conditions between concrete and steel materials play key roles in ensuring the composite effect and load-carrying capacity of concrete-steel composite structures such as concrete-filled steel tube (CFST) members in practice. A method using both surface wave and electromechanical impedance (EMI) measurement for detecting the existence and the location of inaccessible interface debonding defects between the concrete core and steel tube in CFST members using piezoelectric lead zirconate titanate (PZT) patches as actuators and sensors is proposed. A rectangular CFST specimen with two artificially mimicked interface debonding defects was experimentally verified using PZT patches as the actuator and sensor. By comparing the surface wave measurement of PZT sensors at different surface wave travelling paths under both a continuous sinusoidal signal and a 10-period sinusoidal windowed signal, three potential interface debonding defects are quickly identified. Furthermore, the accurate locations of the three detected potential interface debonding defects are determined with the help of EMI measurements from a number of additional PZT sensors around the three potential interface debonding defects. Finally, the accuracy of the proposed interface debonding detection method is verified with a destructive observation by removing the local steel tube at the three detected interface debonding locations. The observation results show that the three detected interface debonding defects are two mimicked interface debonding defects, and an unexpected debonding defect occurred spontaneously due to concrete shrinkage in the past one and a half years before conducting the test. Results in this study indicate that the proposed method can be an efficient and accurate approach for the detection of unknown interface debonding defects in existing CFST members.

Reducing nonradiative recombination for highly efficient inverted perovskite solar cells via a synergistic bimolecular interface.

Reducing interface nonradiative recombination is important for realizing highly efficient perovskite solar cells. In this work, we develop a synergistic bimolecular interlayer (SBI) strategy via 4-methoxyphenylphosphonic acid (MPA) and 2-phenylethylammonium iodide (PEAI) to functionalize the perovskite interface. MPA induces an in-situ chemical reaction at the perovskite surface via forming strong P-O-Pb covalent bonds that diminish the surface defect density and upshift the surface Fermi level. PEAI further creates an additional negative surface dipole so that a more n-type perovskite surface is constructed, which enhances electron extraction at the top interface. With this cooperative surface treatment, we greatly minimize interface nonradiative recombination through both enhanced defect passivation and improved energetics. The resulting p-i-n device achieves a stabilized power conversion efficiency of 25.53% and one of the smallest nonradiative recombination induced Voc loss of only 59 mV reported to date. We also obtain a certified efficiency of 25.05%. This work sheds light on the synergistic interface engineering for further improvement of perovskite solar cells.

UBE2I regulates the nuclear translocation of hnRNPA2B1 by contributing to SUMO modification in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a progressive condition affecting the joints that lacking effective therapy. However, the underlying molecular mechanism has not been fully clarified. METHODS: A model of OA was established in Sprague-Dawley (SD) rats through intra-articularly injected with monoiodoacetate (MIA). Western blot analysis was used to identify the levels of UBE2I and hnRNPA2B1 in articular cartilage. Overexpression and siRNA vectors for UBE2I were constructed and transfected into rat chondrocytes. CCK-8, TUNEL and transwell assay were utilized to assess the cell viability, apoptosis and migration ability. Western blot analysis was used to determine the levels of chondrogenic-specific genes including SOX9, COL2A1, Aggrecan, and PRG4. Then, molecular interactions were confirmed by immunoprecipitation. RESULTS: We observed significant upregulation of UBE2I and hnRNPA2B1 expression in articular cartilage samples of OA. The Pearson correlation analysis revealed positive correlation between UBE2I and hnRNPA2B1 levels. Functional experiments showed that increased UBE2I expression significantly suppressed cell growth, migration, and reduced the expression of chondrogenic-specific genes, while decreasing UBE2I levels had the opposite effects. Molecular interactions between UBE2I and hnRNPA2B1were determined via co-localization and immunoprecipitation. SUMO1 and SUMO3 proteins were enriched by immunoprecipitation using hnRNPA2B1 antibodies. Rescue experiments were performed using SUMOylation inhibitor (2-D08) and SUMOylation activator (N106). Overexpression of UBE2I increased the expression of hnRNPA2B1 in the cytoplasm and decreased the level in the nucleus, which was reversed by the treatment of 2-D08. Conversely, UBE2I knockdown and N106 treatment had the opposite effect. CONCLUSIONS: UBE2I modulated the nuclear translocation of hnRNPA2B1 by promoting SUMOylation in OA.

Assessing genotoxic effects of chemotherapy agents by a robust in vitro assay based on mass spectrometric quantification of γ-H2AX in HepG2 cells.

Chemotherapy has already proven widely effective in treating cancer. Chemotherapeutic agents usually include DNA damaging agents and non-DNA damaging agents. Assessing genotoxic effect is significant during chemotherapy drug development, since the ability to attack DNA is the major concern for DNA damaging agents which relates to the therapeutic effect, meanwhile genotoxicity should also be evaluated for chemotherapy agents' safety especially for non-DNA damaging agents. However, currently applicability of in vitro genotoxicity assays is hampered by the fact that genotoxicity results have comparatively high false positive rates. γ-H2AX has been shown to be a bifunctional biomarker reflecting both DNA damage response and repair. Previously, we developed an in vitro genotoxicity assay based on γ-H2AX quantification using mass spectrometry. Here, we employed the assay to quantitatively assess the genotoxic effects of 34 classic chemotherapy agents in HepG2 cells. Results demonstrated that the evaluation of cellular γ-H2AX could be an effective approach to screen and distinguish types of action of different classes of chemotherapy agents. In addition, two crucial indexes of DNA repair kinetic curve, i.e., k (speed of γ-H2AX descending) and t50 (time required for γ-H2AX to drop to half of the maximum value) estimated by our developed online tools were employed to further evaluate nine representative chemotherapy agents, which showed a close association with therapeutic index or carcinogenic level. The present study demonstrated that mass spectrometric quantification of γ-H2AX may be an appropriate tool to preliminarily evaluate genotoxic effects of chemotherapy agents.

How can green finance effectively promote low-carbon cities? Evidence from 237 cities in China.

Urban areas contribute 85% of China's CO2 emissions. Green finance is an important means to support green energy development and achieve the low-carbon transformation of high-energy-consuming industries. The motivation of this article is to investigate the impact and mechanism of green finance on urban carbon intensity. Most existing literature uses linear models to investigate urban carbon intensity, ignoring the nonlinear relationships between economic variables. The nonparametric models can fill the inherent shortcomings of linear models and effectively simulate the nonlinear nexus between economic variables. Based on the 2011-2021 panel data of 237 cities in China, this paper applies the nonparametric additive model to survey the influence of green finance on urban carbon intensity. Empirical findings exhibit that green finance exerts an inverted U-shaped effect on urban carbon intensity, indicating that the carbon reduction effect of green finance has gradually shifted from inconspicuous in the early stages to prominent in the later stages. Then, from the perspectives of region, city size, and carbon intensity, this article conducts heterogeneity analysis. The results show that the impact of green finance on various carbon intensities all exhibits obvious nonlinear feature. Furthermore, this article employs a mediation effect model to conduct mechanism analysis. The results display that technological progress and industrial structure are two important mediating variables, both of which produce an inverted U-shaped nonlinear impact on urban carbon intensity.

Assessing the efficacy of a graded pulmonary rehabilitation protocol in mechanically ventilated patients following brainstem hemorrhage.

BACKGROUND: The objective of this study is to assess the impact of an early-graded pulmonary rehabilitation training program on patients undergoing mechanical ventilation due to brainstem hemorrhage. METHODS: Eighty patients receiving mechanical ventilation due to brainstem hemorrhage at our hospital's neurosurgery department between August 2022 and October 2023 were enrolled as participants. A sampling table was generated based on the order of admission, and 80 random sequences were generated using SPSS software. These sequences were then sorted in ascending order, with the first half designated as the control group and the second half as the intervention group, each comprising 40 cases. The control group received standard nursing care for mechanical ventilation in brainstem hemorrhage cases, while the intervention group underwent early-graded pulmonary rehabilitation training in addition to standard care. This intervention was conducted in collaboration with a multidisciplinary respiratory critical care rehabilitation team. The study compared respiratory function indices, ventilator weaning success rates, ventilator-associated pneumonia incidence, mechanical ventilation duration, and patient discharge duration between the 2 groups. RESULTS: The comparison between patients in the observation group and the control group regarding peak expiratory flow and maximum inspiratory pressure on days 1, 3, 5, and 7 revealed statistically significant differences (P < .05). Additionally, there was a statistically significant interaction between the main effect of intervention and the main effect of time (P < .05). The success rate of ventilator withdrawal was notably higher in the observation group (62.5%) compared to the control group (32.5%), with a statistically significant difference (P < .05). Moreover, the incidence rate of ventilator-associated pneumonia was significantly lower in the observation group (2.5%) compared to the control group (17.5%) (P < .05). Furthermore, both the duration of mechanical ventilation and hospitalization were significantly shorter in the observation group compared to the control group (P < .05). CONCLUSION: Early-graded pulmonary rehabilitation training demonstrates effectiveness in enhancing respiratory function, augmenting the ventilator withdrawal success rate, and reducing both the duration of mechanical ventilation and hospitalization in mechanically ventilated patients with brainstem hemorrhage. These findings suggest the potential value of promoting the application of this intervention in clinical practice.

Cellulose nanocrystal-infused polymer hydrogel imbued with ferric-manganese oxide nanoparticles for efficient antinomy removal.

Antimony is a highly poisonous pollutant that needs to be removed from water to ensured safety. In this work, we have fabricated a novel adsorbent, the ferric-manganese oxide (FeMnOx) nanoparticles embedded cellulose nanocrystal-based polymer hydrogel (FeMnOx @CNC-g-PAA/qP4VP, denoted as FMO@CPqP), specifically engineered for the remediation of antimony-laden water. Comprehensive evaluations have been conducted to investigate the efficacy of the FMO@CPqP hydrogel in removal of antimony from water. The hydrogel exhibits superior affinity for antimony, with maximum adsorption capacities of 276.1 mg/g for Sb(III) and 286.8 mg/g for Sb(V). The adsorptive dynamics, governed by the kinetics and isotherm analyses, elucidate that the immobilization of both Sb(III) and Sb(V) is facilitated through a homogeneous and monolayer chemisorption mechanism. The hydrogel has a three-dimensional interconnected porous structure and exhibits good swelling behavior, which facilitates the rapid absorption of antimony ions by this high surface area hydrogel into the channels. Furthermore, various effects, including the oxidation and inner-sphere coordination mediated by FeMnOx NPs and the electrostatic attractions of the quaternized P4VP chains, promote the immobilization of antimony species. Owing to its high removal efficiency, stability and reusability, the FMO@CPqP hydrogel emerges as an exemplary candidate for the removal of antimony contaminants in water treatment processes.

The prerequisites and clinical outcomes of ipsilateral C7 nerve root transfer to the upper trunk for adult C5-C6 brachial plexus injuries.

PURPOSE: Although ipsilateral C7 nerve transfer is used for the treatment of C5-C6 brachial plexus injuries, accurately evaluating the functional quality of the donor nerve (ipsilateral C7 nerve root) is difficult, especially when the C7 nerve root is slightly injured. The purpose of this study was to determine the indicators to evaluate the quality of the ipsilateral C7 nerve and assess the clinical outcomes of this procedure. METHODS: This study employed the following three indicators to assess the quality of the ipsilateral C7 nerve: (1) the muscle strength and electrophysiological status of the latissimus dorsi, triceps brachii, and extensor digitorum communis; (2) the sensibility of the radial three digits, especially the index finger; and (3) the intraoperative appearance, feel and electrophysiological status of the ipsilateral C7 nerve root. Transfer of the ipsilateral C7 nerve root to the upper trunk was implemented only when the following three tests were conducted, the criteria were met, and the clinical outcomes were assessed in eight patients with C5-C6 brachial plexus injuries. RESULTS: Patients were followed-up for an average of 90 ± 42 months. At the final follow-up, all eight patients achieved recovery of elbow flexion, with five and three patients scoring M4 and M3, respectively, according to the Medical Research Council scoring. The shoulder abduction range of motor recovery averaged 86 ± 47° (range, 30°-170°), whereas the shoulder external rotation averaged 51 ± 26° (range, 15°-90°). CONCLUSION: Ipsilateral C7 nerve transfer is a reliable and effective option for the functional reconstruction of the shoulder and elbow after C5-C6 brachial plexus injuries when the three prerequisites are met.

Development and validation of a preoperative radiomics-based nomogram to identify patients who can benefit from splenic hilar lymphadenectomy: a pooled analysis of three prospective trials.

BACKGROUND: We aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR≤0.4, and sLNR>0.4. Patients in the D2+No. 10 group were randomly divided into the training (n=302) and validation (n=130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate and high SHLN metastasis burden groups (LMB, MMB and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) (P<0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

ScHGSC-IGDC: Identifying genes with differential correlations of high-grade serous ovarian cancer based on single-cell RNA sequencing analysis.

Due to the high heterogeneity of ovarian cancer (OC), it occupies the main cause of cancer-related death among women. As the most aggressive and frequent subtype of OC, high-grade serous cancer (HGSC) represents around 70 % of all patients. With the booming progress of single-cell RNA sequencing (scRNA-seq), unique and subtle changes among different cell states have been identified including novel risk genes and pathways. Here, our present study aims to identify differentially correlated core genes between normal and tumor status through HGSC scRNA-seq data analysis. R package high-dimension Weighted Gene Co-expression Network Analysis (hdWGCNA) was implemented for building gene interaction networks based on HGSC scRNA-seq data. DiffCorr was integrated for identifying differentially correlated genes between tumor and their adjacent normal counterparts. Software Cytoscape was implemented for constructing and visualizing biological networks. Real-time qPCR (RT-qPCR) was utilized to confirm expression pattern of new genes. We introduced ScHGSC-IGDC (Identifying Genes with Differential Correlations of HGSC based on scRNA-seq analysis), an in silico framework for identifying core genes in the development of HGSC. We detected thirty-four modules in the network. Scores of new genes with opposite correlations with others such as NDUFS5, TMSB4X, SERPINE2 and ITPR2 were identified. Further survival and literature validation emphasized their great values in the HGSC management. Meanwhile, RT-qPCR verified expression pattern of NDUFS5, TMSB4X, SERPINE2 and ITPR2 in human OC cell lines and tissues. Our research offered novel perspectives on the gene modulatory mechanisms from single cell resolution, guiding network based algorithms in cancer etiology field.

[Construction of a Predictive Model for Diabetes Mellitus Type 2 in Middle-Aged and Elderly Populations Based on the Medical Checkup Data of National Basic Public Health Service]. / åŸºäºŽå›½å®¶åŸºæœ¬å ¬å ±å«ç”ŸæœåŠ¡ä½“æ£€çš„ä¸­è€å¹´äºº2åž‹ç³–å°¿ç— é£Žé™©é¢„æµ‹æ¨¡åž‹æž„å»º.

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.

[A nomogram for predicting residual back pain after percutaneous vertebroplasty for osteoporotic vertebral compression fractures].

OBJECTIVE: To construct percutaneous vertebroplasty for predicting osteoporotic vertebral compression fractures (OVCFs) nomogram of residual back pain (RBP) after percutaneous vertebroplasty(PVP). METHODS: Clinical data of 245 OVCFs patients who were performed PVP from January 2020 to December 2022 were retrospectively analyzed, including 47 males and 198 females, aged from 65 to 77 years old with an average of (71.47±9.03) years old, and were divided into RBP group and non-RBP group according to whether RBP occurred. Gender, age, comorbidities, fracture stage, body mass index (BMI), bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI) and other general information were collected; anterior vertebral height (AVH), anterior vertebral height ratio (AVH), anterior vertebral height ratio(AVHR), Cobb angle, intravertebral vacuum cleft (IVC), thoracolumbar fascia (TLF) injury, paravertebral muscle steatosis, injection volume and leakage of bone cement, bone cement dispersion pattern, anterior vertebral height recovery ratio (AVHRR), Cobb angle changes, etc. imaging parameters before operation and 24 h after operation were collected. Univariate analysis was performed to analysis above factors, and multivariate Logistic regression model was used to investigate independent risk factors for postoperative RBP, and Nomogram model was constructed and verified;receiver operating characteristic(ROC) curve and calibration curve were used to determine predictive performance and accuracy of the model, and Hosmer-Lemeshow (H-L) test was used for evaluation. The area under curve (AUC) of ROC was calculated, and Harrell consistency index (C index) was used to evaluate the predictive efficiency of model;decision curve analysis (DCA) was used to evaluate clinical practicability of model. RESULTS: There were 34 patients in RBP group and 211 patients in non-RBP group. There were no significant differences in gender, age, comorbidities, fracture stage, BMI, BMD, VAS, ODI, AVH, AVHR and Cobb angle between two groups (P>0.05). Univariate analysis showed 6 patients occurred IVC in RBP group and 13 patients in non-RBP, the number of IVC in RBP group was higher than that in non-RBP group (χ2=5.400, P=0.020);6 patients occuured TLF injury in RBP group and 11 patients in non-RBP group, the number of TLF injury in RBP group was higher than that in non-RBP group (χ2=7.011, P=0.008);In RBP group, 18 patients with grade 3 to 4 paraptebral steatosis and 41 patients in non-RBP group, RBP group was higher than non-RBP group (χ2=21.618, P<0.001), and the proportion of bone cement mass in RBP group was higher than non-RBP group (χ2=6.836, P=0.009). Multivariate Logistic regression analysis showed IVC (χ2=4.974, P=0.025), TLF injury (χ2=5.231, P=0.023), Goutallier grade of paravertebral steatosis >2 (χ2=15.124, P<0.001) and proportion of bone cement (χ2=4.168, P=0.038) were independent risk factors for RBP after PVP. ROC curve of model showed AUC of original model was 0.816[OR=2.862, 95%CI (0.776, 0.894), P<0.001]. The internal verification of model through 200 bootstrap samples showed the value of C index was 0.936, and calibration curve showed predicted probability curve was close to actual probability curve. H-L goodness of fit test results were χ2=5.796, P=0.670. DCA analysis results showed the decision curve was above None line and All line when the threshold value ranged from 6% to 71%. CONCLUSION: IVC, TLF combined injury, paravertebral muscle steatosis with Goutallier grade> 2, and bone cement diffusion with mass type are independent risk factors for RBP after PVP. The risk prediction model for RBP after PVP established has good predictive performance and good clinical practicability.

Efficient Near-Infrared Fluorophores Based on Cyanostyrene Derivatives for Two-Photon Fluorescence Bioimaging.

Organic fluorescent materials with red/near-infrared (NIR) emission are highly promising for use in biotechnology due to their exceptional advantages. However, traditional red/NIR fluorophores often exhibit weak emission at high concentrations or in an aggregated state due to the aggregate-caused quenching effect, which severely limits their applicability in biological imaging. To address this challenge, we developed a series of cyanostyrene derivatives with aggregation-induced emission characteristics, including 2,3-Bis-(4-styryl-phenyl)-but-2-enedinitrile (DPB), 2,3-Bis-{4-[2-(4-methoxy- phenyl)-vinyl]-phenyl}-but-2-enedinitrile (DOB), 2,3-Bis-{4-[2-(4-diphenylamino- phenyl)-vinyl]-phenyl}-but-2-enedinitrile (DTB), and 2,3-Bis-[4-(2-{4-[phenyl- (4-triphenylvinyl-phenyl)-amino]-phenyl}-vinyl)- phenyl]-but-2-enedinitrile (DTTB). Notably, these compounds exhibited intense solid state fluorescence owing to AIE effect, especially DTTB shows NIR emission with high solid state quantum efficiency (712 nm, ΦF=14.2%). Then we prepared DTTB@PS-PEG NPs nanoparticles by encapsulating DTTB with the amphiphilic polymer polystyrene-polyethylene glycol (PS-PEG). Importantly, DTTB@PS-PEG NPs exhibited highly efficient NIR luminescence (ΦF=28.7%) and a large two-photon absorption cross-section (1900 GM) under 800 nm laser excitation. The bright two-photon fluorescence of DTTB@PS-PEG indicated that it can be a highly promising candidate for two-photon fluorescence probe. Therefore, this work provides valuable insights for the design of highly efficient and NIR-emitting two-photon fluorescent probes.

16th GCC Closed Forum: ICH M10 implementation; NGS, qPCR/dPCR, flow cytometry validation; tissue biomarkers; IS response; immunogenicity harmonization; bioanalytical industry status.

The 16th GCC Closed Forum was held in Orlando, FL, USA, on 23 June 2023. Representatives from international bioanalytical Contract Research Organizations were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: IS response, flow cytometry, changes to the bioanalytical industry, NGS assays, biomarker assay for tissues, dPCR validation, immunogenicity harmonization and ICH M10 implementation. Conclusions and consensus from discussions of these topics are included in this article.