Unveiling the Twisted Aromatic Donor Effect on the Nonlinear Response of D-π-A Type Malononitrile-Derived Chromophores.

This study presents the design, synthesis, and comprehensive characterization of a novel series of D-π-A type malononitrile-derived chromophores, BTC-1 to BTC-4. Combining various spectroscopic techniques, nonlinear Z-scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (µ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and ICT collectively dictate the nonlinear optical properties of the compounds. Notably, BTC-1 exhibits an exceptional nonlinear absorption coefficient ß value (2 × 10-8 m W-1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high-performance organic NLO materials with potential applications in advanced photonic devices.

Non-invasive measurement of rat auditory evoked fields using an optically pumped atomic magnetometer: Effects of task manipulation.

Optically pumped magnetometers (OPMs) have become a favorable tool for magnetoencephalography (MEG) measurement, offering a non-invasive method of measurement. OPMs do not require cryogenic environments, sensors can be more closely aligned with the brain. We employed a passive single-stimulus paradigm in conjunction with OPMs with a sensitivity of 20 fT/ Hz to investigate the auditory response of rats to inter-stimulus interval (ISI) and frequencies, recording the rat auditory event-related magnetic fields (ERMFs). Our findings include: (1) Auditory evoked fields can be detected non-invasively by OPMs; (2) The amplitude of the rat auditory ERMFs varies with changes in ISI, with more pronounced amplitude changes observed after 5 s; (3) When the sound stimulus frequency is altered at the same ISI, the amplitude of the rats ERMFs changes with frequency, indicating significant differences in attention. Our method offers a valuable tool for the clinical application of a single stimulus paradigm and opens up a new avenue for research on the brain magnetic field detections.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes.

AIM: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δß|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR. CONCLUSION: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

The Dynamics of Per- and Polyfluoroalkyl Substances (PFAS) at Interfaces in Porous Media: A Computational Roadmap from Nanoscale Molecular Dynamics Simulation to Macroscale Modeling.

Managing and remediating perfluoroalkyl and polyfluoroalkyl substance (PFAS) contaminated sites remains challenging. The major reasons are the complexity of geological media, partly unknown dynamics of the PFAS in different phases and at fluid-fluid and fluid-solid interfaces, and the presence of cocontaminants such as nonaqueous phase liquids (NAPLs). Critical knowledge gaps exist in understanding the behavior and fate of PFAS in vadose and saturated zones and in other porous media such as concrete and asphalt. The complexity of PFAS-surface interactions warrants the use of advanced characterization and computational tools to understand and quantify nanoscale behavior of the molecules. This can then be upscaled to the microscale to develop a constitutive relationship, in particular to distinguish between surface and bulk diffusion. The dominance of surface diffusion compared to bulk diffusion results in the solutocapillary Marangoni effect, which has not been considered while investigating the fate of PFAS. Without a deep understanding of these phenomena, derivation of constitutive relationships is challenging. The current Darcy scale mass-transfer models use constitutive relationships derived from either experiments or field measurements, which makes their applicability potentially limited. Here we review current efforts and propose a roadmap for developing Darcy scale transport equations for PFAS. We find that this needs to be based on systematic upscaling of both experimental and computational studies from nano- to microscales. We highlight recent efforts to undertake molecular dynamics simulations on problems with similar levels of complexity and explore the feasibility of conducting nanoscale simulations on PFAS dynamics at the interface of fluid pairs.

Role of Macrophage Activation and Polarization in Myocardial Fibrosis and Intervention of Traditional Chinese Medicine / 中国实验方剂学杂志

Myocardial fibrosis （MF） is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells， the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself， and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research， scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system （RAAS） system and the inflammatory process， repairing the extracellular matrix， managing oxidative stress， and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process， macrophage activation is beneficial， but excessive activation will be harmful. In the early stage of MF， appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF， appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient， or the balance of M1/M2 macrophage polarization is broken， the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin， as well as regulating Qi and activating blood， but there are also some heat-clearing， dampness-drying， and detoxification products. Therefore， the occurrence of MF may be caused by Qi and Yin deficiency， damp heat accumulation， and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF， this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF， so as to provide a reference for the treatment of MF with traditional Chinese medicine.

The significance of intratumoral and peritumoral radiomics models in predicting occult lymph node metastasis in stage T1 non-small cell lung cancer / 实用放射学杂志

Objective To investigate the significance of intratumoral and peritumoral radiomics models in predicting occult lymph node metastasis in stage T1 non-small cell lung cancer(NSCLC)and to compare the predictive accuracy in different peritumoral radiomics models.Methods The CT images and clinical data of 211 patients without lymph node metastasis on preoperative CT examination and pathologically confirmed NSCLC after surgery were collected.The radiomics features were derived from the three-dimensional volume of interest(VOI)of the intratumoral and peritumoral at 3-,5-,and 10-mm following lesion segmentation on CT images of each patient.The feature data of all nidus were radomly divide into training set and validation set with a ratio of 7︰3.The Pearson or Spearman correlation test was performed to remove redundancy.Dimensionality was reduced by the least absolute shrinkage and selection operator(LASSO)regression analysis.The linear combination of selected features and corresponding coefficients were used to construct the Radiomics score(Radscore).The clinical model and comprehensive model were constructed by logistic regression analysis.The conprehensive model was visualized with the nomogram,and its performance was evaluated.Results Among the peritumoral radiomics models,the peritumoral 5-mm model showed the best predictive efficacy[validation set,area under the curve(AUC)0.771].The comprehensive model containing Radscore,CT image features and CEA exhibited the best performance(validation set,AUC 0.850).Conclusion Intratumoral and peritumoral radiomics models perform efficiently in predicting occult lymph node metastasis in stage T1 NSCLC,and nomogram can effectively and noninvasively predict occult lymph node metastasis in NSCLC.

3D printed metal augment or tibial prosthesis for reconstruction of large bone defects in total knee arthroplasty and revision surgery / 中华骨科杂志

Objective:To investigate the clinical efficacy of 3D printed metal augment or tibial prosthesis for reconstruction of large bone defects in total knee arthroplasty (TKA) and knee revision surgery.Methods:A total of 7 patients (7 knees) with TKA or knee revision who were admitted to the Department of Orthopaedics of the Second Affiliated Hospital of Zhejiang University School of Medicine with large bone defects from July 2018 to December 2023 were retrospectively analyzed, including 4 patients with TKA and 3 patients with knee revision. There were 3 males and 4 females, aged 58.7±7.6 years (range, 54-68 years), 3 patients with left knee and 4 patients with right knee. All the patients had bone defects in the knee joint (AORI type III), 2 cases had bone defects only in the femur, 4 cases had bone defects only in the tibia, and 1 case had bone defects in both the tibia and femur, which were treated with personalized reconstruction using 3D printing. Hip-knee-ankle angles, American Knee Society score (KSS) before and after surgery were compared, and postoperative complications were observed.Results:All patients successfully completed the operation, and the operation time was 189.3±35.5 min (range, 125-240 min). Complex TKA was performed in 4 cases with surgical times of 175, 195, 210, and 240 min, and revision surgery was performed in 3 cases with surgical times of 125, 180, and 200 min, respectively. Intraoperative blood loss was 114±24.4 ml (range, 100-150 ml). Five cases used 3D printed metal augment, and two used 3D printed one-piece tibial components. All patients were followed up for 2, 2, 5, 6, 7, 20, 57 months, respectively. The KSS of the five patients at 3 months postoperatively were 56, 61, 66, 56, and 56 points, respectively, greater than the preoperative scores of 35, 44, 36, 27, and 41 points. The KSS functional scores of the five patients at 3 months postoperatively were 45, 45, 45, 30, and 45 points, respectively, which were greater than the preoperative scores of 30, 30, 15, 20, and 20 points. The hip-knee-ankle angle was 181.8°±3.4° (range, 177.9° to 188.0°) at the final follow-up and 175.8°±12.4° (range, 153.3° to 192.1°) before surgery, with no significant difference ( t=-1.230, P=0.242). At the final follow-up, the 3D printed component was well integrated with the bone surface, the prosthesis was securely positioned, and the force lines of the lower limbs were normal. There were no postoperative complications such as poor wound healing, infection, fat liquefaction, nerve injury, deep vein thrombosis of lower limbs, knee joint stiffness, periprosthesis infection and loosening. Conclusion:Using 3D printed metal augment or tibial prosthesis to reconstruct the huge bone defect in TKA and revision has a satisfactory early clinical effect, satisfactory joint function and good surgical safety.

Effect of FoxO1 on Cardiomyocyte Apoptosis and Inflammation in Viral Myocarditis via Modultion of the TLR4/NF-κB Signaling Pathway.

To investigate the possible effect of FoxO on coxsackievirus B3 (CVB3) -induced cardiomyocyte inflammation and apoptosis via modulation of the TLR4/NF-κB signaling pathway.Viral myocarditis (VMC) models were establied via CVB3 infection both in vivo and in vitro. Western blotting was adopted to detect FoxO1 and TLR4 expressions in myocardial tissues and cells. Cardiomyocytes of suckling mouse were divided into the control, CVB3, CVB3 + pcDNA, CVB3 + pcDNA-FoxO1, CVB3 + TLR4 siRNA, and CVB3 + pcDNA-FoxO1 + TLR4 siRNA groups. Flow cytometry was employed to evaluate cell apoptosis. The expressions of inflammatory factors including TNF-α, IL-1ß, and IL-6 were detected via quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Then, TLR4/NF-κB pathway-related proteins were determined via Western blotting.VMC mice had increased FoxO1 and TLR4 expressions in myocardial tissues. Cardiomyocytes with CVB3 infection also had upregulated protein expressions of p-FoxO1/FoxO1 and TLR4. Compared with those in the control group, the cardiomyocytes in the CVB3 group were increased in LDH and CK-MB levels, cell apoptosis rate and inflammatory factors (TNF-α, IL-1ß and IL-6), as well as protein expressions of TLR4 and p-p65/p65. Compared with those in the CVB3 group, the cardiomyocytes in the CVB3 + pcDNA-FoxO1 group were further upregulated whereas those in the CVB3 +TLR4 siRNA group were downregulated in the aforementioned indicators. Furthermore, TLR4 siRNA can reverse the effect of pcDNA-FoxO1 on the aggravation of cardiomyocyte injury induced by CVB3 infection.FoxO1 can upregulate the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced VMC.

Changes and related factors of blood CCN1 levels in diabetic patients.

Objective: To study the differences in blood cellular communication network factor 1 (CCN1) levels between patients with diabetes mellitus (DM) and healthy individuals and to explore the relationship between CCN1 and diabetic retinopathy (DR). Methods: Plasma CCN1 levels were detected using ELISA in 50 healthy controls, 74 patients with diabetes without diabetic retinopathy (DM group), and 69 patients with diabetic retinopathy (DR group). Correlations between CCN1 levels and age, body mass index, mean arterial pressure, hemoglobin A1c, and other factors were analyzed. The relationship between CCN1 expression and DR was explored using logistic regression after adjusting for confounding factors. Blood mRNA sequencing analysis was performed for all subjects, and the molecular changes that may be related to CCN1 were explored. The retinal vasculature of streptozotocin-induced diabetic rats was examined using fundus fluorescein angiography; in addition, retinal protein expression was examined using western blotting. Results: Plasma CCN1 levels in patients with DR were significantly higher than in the control and DM groups; however, no significant differences were observed between healthy controls and patients with DM. CCN1 levels negatively correlated with body mass index and positively correlated with the duration of diabetes and urea levels. It was observed that high (OR 4.72, 95% CI: 1.10-20.25) and very high (OR 8.54, 95% CI: 2.00-36.51) levels of CCN1 were risk factors for DR. Blood mRNA sequencing analysis revealed that CCN1-related pathways were significantly altered in the DR group. The expression of hypoxia-, oxidative stress-, and dephosphorylation-related proteins were elevated, while that of tight junction proteins were reduced in the retinas of diabetic rats. Conclusion: Blood CCN1 levels are significantly elevated in patients with DR. High and very high levels of plasma CCN1 are risk factors for DR. Blood CCN1 level may be a potential biomarker for diagnosis of DR. The effects of CCN1 on DR may be related to hypoxia, oxidative stress, and dephosphorylation.

Tyrosinase Inhibitory Peptides from Enzyme Hydrolyzed Royal Jelly: Production, Separation, Identification and Docking Analysis.

Tyrosinase is inextricably related to the development of Alzheimer's disease. The effects of natural tyrosinase inhibitors on human health have attracted widespread attention. This study aimed to isolate and analyze the tyrosinase (TYR) inhibitory peptides in the enzymatic digestion products of royal jelly. We first analyzed optimal process conditions for the enzymatic digestion of royal jelly by single-factor and orthogonal experiments and then used gel filtration chromatography to obtain five fractions (D1~D5) with molecular weights ranging from 600 to 1100 Da. LC-MS/MS was applied to identify the fractions with the highest activity, and the obtained peptides were screened and molecularly docked using AutoDock Vina. The results showed that the optimal enzymatic conditions for tyrosinase inhibition rate were acid protease, enzyme addition 10,000 U/g, initial pH 4, feed-to-liquid ratio 1:4, enzymatic temperature 55 °C, and enzymatic time 4 h. The D4 fraction had the most significant TYR inhibitory activity. The IC50 values of the three new peptides with the strongest TYR inhibitory activity, TIPPPT, IIPFIF, and ILFTLL, were obtained as 7.59 mg/mL, 6.16 mg/mL, and 9.25 mg/mL, respectively. The molecular docking results showed that aromatic and hydrophobic amino acids were more favorable to occupy the catalytic center of TYR. In conclusion, the new peptide extracted from royal jelly has the potential to be used as a natural TYR inhibitory peptide in food products with health-promoting properties.

Phosphatidylglucose alleviates atherosclerosis by increasing cholesterol alienation to bile acids and cholesterol efflux in ApoE-/- mice.

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.

A Comprehensive Review of Natural Flavonoids with Anti-SARS-CoV-2 Activity.

The COVID-19 pandemic caused by SARS-CoV-2 has majorly impacted public health and economies worldwide. Although several effective vaccines and drugs are now used to prevent and treat COVID-19, natural products, especially flavonoids, showed great therapeutic potential early in the pandemic and thus attracted particular attention. Quercetin, baicalein, baicalin, EGCG (epigallocatechin gallate), and luteolin are among the most studied flavonoids in this field. Flavonoids can directly or indirectly exert antiviral activities, such as the inhibition of virus invasion and the replication and inhibition of viral proteases. In addition, flavonoids can modulate the levels of interferon and proinflammatory factors. We have reviewed the previously reported relevant literature researching the pharmacological anti-SARS-CoV-2 activity of flavonoids where structures, classifications, synthetic pathways, and pharmacological effects are summarized. There is no doubt that flavonoids have great potential in the treatment of COVID-19. However, most of the current research is still in the theoretical stage. More studies are recommended to evaluate the efficacy and safety of flavonoids against SARS-CoV-2.

Atomic Magnetometer Achieves Visual Salience Analysis in Drosophila.

An atomic magnetometer (AM) was used to non-invasively detect the tiny magnetic field generated by the brain of a single Drosophila. Combined with a visual stimulus system, the AM was used to study the relationship between visual salience and oscillatory activity of the Drosophila brain by analyzing changes in the magnetic field. Oscillatory activity of Drosophila in the 1-20 Hz frequency band was measured with a sensitivity of 20 fT/Hz. The field in the 20-30 Hz band under periodic light stimulation was used to explore the correlation between short-term memory and visual salience. Our method opens a new path to a more flexible method for the investigation of brain activity in Drosophila and other small insects.

Research progress of DNA-PK inhibitors in the cancer treatment / 药学学报

The most toxic DNA damage is DNA double strand breaks (DSBs), which are mainly repaired by non-homologous end joining (NHEJ). DNA-dependent protein kinase (DNA-PK) belongs to phosphatidylinositol-3-kinase-related protein kinase family (PIKK) and plays a key role in NHEJ. DNA-PK is overexpressed in a variety of cancer cells and is related to the occurrence, development and drug resistance of malignant tumors. In this article, the representative DNA-PK inhibitors with anticancer effects are reviewed, in order to provide a reference to discovery novel DNA-PK inhibitors.

Effect of miR200a and SIRT1 expression on epithelial cell apoptosis in age-related cataract lens epithelial cells / 国际生物医学工程杂志

Objective:To investigate the effects of miR200a and SIRT1 expression on epithelial cell apoptosis in age-related cataract lens epithelial cells.Methods:30 anterior capsule samples of age-related cataract patients were enrolled from the ophthalmology outpatient department of Beichen Hospital affiliated with Nankai University from January to August 2022 as the cataract group and another 30 normal anterior capsule samples of corneal transplantation were enrolled during the same period as the control group. Real -time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression levels of miR200a and SIRT1 genes in the cataract group and control group. The oxidative stress level divided human lens epithelial cells SRA01/04 into a negative control group, miR200a overexpression group, and miR200a inhibition group. The negative control group, miR200a overexpression plasmid, and miR200a inhibitor group were transfected, respectively. Cell apoptosis rate and oxidative stress level were detected by flow cytometry, and Western Blot was used to detect the expression of SIRT1 protein and Caspase-3, Bcl-2, and Bcl-2 related X (Bax) proteins containing cysteine in each group of cells. The targeting relationship between miR200a and SIRT1 was validated using dual luciferase reporter gene detection. Results:Compared with the control group, the expression level of miR200a in the cataract group was significantly increased ( P < 0.01), while the expression level of SIRT1 was significantly reduced ( P < 0.01). Compared with the control group, the levels of SOD, GSH, and GSH-Px in the cataract group were significantly reduced (all P < 0.01), and the MDA level was significantly higher than those in the control group ( P < 0.01). The apoptosis rate of the miR200a overexpression group was significantly higher than that of the negative control group ( P < 0.05), and the apoptosis rate of the miR200a inhibition group was significantly lower than that of the negative control group, the differences were statistically significant ( P < 0.05). The level of SIRT1 protein in the miR200a overexpression group was significantly lower than that in the negative control group ( P < 0.05), and the level of SIRT1 protein in cells of the miR200a inhibition group was significantly higher than that of the negative control group ( P < 0.05). Compared with the negative control group, the miR200a overexpression group showed a significant increase in Caspase-3 activity and Bax protein (all P < 0.05), while the Bcl-2 protein level was significantly reduced ( P < 0.05). The miR200a inhibition group showed a significant decrease in Caspase-3 activity and Bax protein (all P < 0.05), while the Bcl-2 protein level was significantly increased ( P < 0.05). The dual luciferase experiment showed that the overexpression group of miR-200a can significantly inhibit the luciferase activity of the wild-type SIRT1 plasmid, which is the target gene of miR-200a. Conclusions:miR220a is highly expressed in the capsule of lens of patients with age-related cataracts, and its mechanism may be that miR220a promotes apoptosis of lens epithelial cells by targeting the expression of SIRT1.

Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL).@*METHODS@#Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits.@*RESULTS@#It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated.@*CONCLUSION@#Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

Acupuncture and moxibustion in treatment of chronic obstructive pulmonary disease at stable stage: a network Meta-analysis / 中国针灸

The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: ① For the forced expiratory volume in one second predicted (FEV1%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). ② Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ③ Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV1%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.

Prospect on medical treatment of pulmonary mucinous adenocarcinoma / 中国综合临床

Pulmonary mucinous adenocarcinoma is a subtype of lung adenocarcinoma, among which invasive mucinous adenocarcinoma (IMA) is the most common subtype and is easily misdiagnosed as pneumonia. Its etiology and pathogenesis are unclear and may be related to gene mutations and other factors. Due to its relative rarity and few related studies, guidelines do not provide advices on its treatment. KRAS mutations are common in IMA patients, and Sotorasib may be effective against KRAS G12C mutated IMA. NRG1 fusion is considered to be an important driver of IMA, and afatinib may be effective in treating IMA with NRG1 fusion/rearrangement. PD-L1 expression is very low in IMA patients, while B7-H3 expression is high, so B7-H3 may be a potential immunotherapeutic target.

High-throughput screening of differential expression of exosomal miRNAs in DeBakey typeⅠacute aortic dissection patients / 中国胸心血管外科临床杂志

@#Objective    To evaluate the changes in the expression and significance of serum exosomal miRNAs in patients with DeBakey typeⅠacute aortic dissection (AAD). Methods    Twelve male patients with AAD and six healthy male medical examiners from our hospital were retrospectively included in this study. According to the time of chest pain, the AAD patients were divided into an AAD group within 24 h of chest pain onset, aged 47.00±8.79 years and an AAD group within 48 h of chest pain onset, aged 50.17±9.99 years. The healthy males were allocated to a control group, aged 49.17±4.26 years. Serum exosomal miRNAs were isolated, identified and quantified, and then differentially expressed exosomal miRNAs were screened. The bioinformatic analyses such as GO and KEGG were performed on the differentially expressed exosomal miRNAs. Results    High-throughput screening results revealed differential expression of AAD serum exosomal miRNAs. The upregulated miRNAs of AAD groups was hsa-miR-574-5p (P<0.05), and downregulated miRNAs were hsa-miR-223-3p, hsa-miR-146b-5p, hsa-miR-15b-5p, and hsa-miR-155-5p (P<0.05). Further bioinformatic analysis of the above miRNAs revealed that they were mainly enriched in signaling pathways such as transforming growth factor-β, cell cycle and endoplasmic reticulum protein synthesis. Conclusion    Differential expressions of serum exosomal miRNAs in AAD patients may be related to the pathogenesis of AAD, providing new ideas and clues for further exploration of AAD diagnostic markers and pathogenesis.