Influence of quercetin on aging of bone marrow mesenchymal stem cells induced by microgravity / 中国药理学通报

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Application of two different methods of visual acuity assessment for myopia screening among lower grade elementary school students / 中国学校卫生

Objective@#To explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability.@*Methods@#From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated.@*Results@#The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2.@*Conclusions@#Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Establishment and validation of prognosis prediction model for patients with gallbladder cancer based on albumin-bilirubin grade / 中华肝胆外科杂志

Objective:To establish and validate a prognosis prediction model of gall bladder cancer after surgery based on the albumin-bilirubin (ALBI) grade.Methods:The clinicopathological data of 161 patients with gallbladder cancer undergoing radical surgery in the First Hospital of Jiaxing between March 2011 to January 2020 were retrospectively analyzed, including 44 males and 117 females, aged (65±9) years old. The patients were grouped by the levels of ALBI score. The survival data were obtained through telephone or outpatient review. The Kaplan-Meier method was used to draw the survival curve. Multivariate analysis was performed using the Cox regression analysis model. The time-dependent receiver operating characteristic (ROC) curve was plotted to compare the prognostic value of the scoring system. A nomogram based on ALBI grade was established and its predictive performance was evaluated.Results:The 1, 3, 5 years overall survival (OS) rates of patients with gallbladder cancer were 76.7%, 52.5%, and 41.9%, respectively. The time-dependent ROC curves revealed that the area under the curve (AUC) values of ALBI grade were 0.659, 0.597 and 0.599 for 1, 2 and 3 years, showing a good prognostic performance. Multivariate regression analysis showed that poorer tumor differentiation ( HR=2.890, 95% CI: 1.816-4.600, P<0.001), TNM Ⅲ/Ⅳ stage ( HR=2.832, 95% CI: 1.781-4.503, P<0.001), ALBI grade 2 ( HR=1.595, 95% CI: 1.017-2.500, P=0.042), and ALBI grade 3 ( HR=3.938, 95% CI: 1.375-11.278, P=0.011) were independent risk factors for OS. The nomogram established with the independent risk factors such as ALBI grade showed a good predictive value for OS. The ROC curve results showed that the AUC values for 1, 3 and 5 years were 0.796, 0.806 and 0.799, respectively. The calibration plots and clinical decision curve analysis (DCA) showed the clinical feasibility of this nomogram. Conclusion:The nomogram model based on ALBI grading has a good predictive value for gallbladder cancer after surgery, which could guide the prognosis and individualized treatment decision-making.

Clinical application of radiotherapy based on UIH linear accelerators to in vivo dose verification / 中华放射医学与防护杂志

Objective:To explore the clinical application of the electronic portal imaging device (EPID) based on the linear accelerator produced by Shanghai United Imaging Healthcare Co., Ltd. (UIH) to in vivo dose verification. Methods:A total of 68 patients (32 cases with head and neck tumors, 16 cases with chest tumors, and 20 cases with abdomen and pelvis tumors) who were treated with volumetric modulated arc therapy (VMAT) in the Henan Provincial People′s Hospital were selected in this study. Each patient underwent the pre-treatment dose verification using an Arccheck device (Pre Arccheck), the pre-treatment dose verification using an EPID (Pre EPID), and the in vivo dose verification using an EPID (In vivo EPID). Moreover, the position verification based on fan beam computed tomography (FBCT) was also performed for each patient in the first three treatments and then once a week. The patients were treated when the setup error in any direction ( x: left-right, y: head-foot, z: vertical) was less than 3 mm; otherwise, position correction would be conducted. The three-dimensional setup deviation d was calculated according to setup errors x, y, and z. Results:The γ passing rates of dose verifications Pre EPID and In vivo EPID of 68 patients were (99.97±0.1)% and (94.15±3.84)%, respectively, significantly different from that (98.86±1.48)% of the Pre Arccheck dose verification ( t = -6.12, 9.43; P < 0.05). The γ passing rates of the chest, abdomen and pelvis, and head and neck in the In vivo EPID dose verification showed no significant differences ( P > 0.05). The difference in the γ passing rates (5.56±3.72)% between dose verifications Pre EPID and first In vivo EPID was unrelated to the three-dimensional setup deviation d (1.46±1.51 mm) ( P > 0.05). As the treatment proceeded, the γ passing rate of In vivo EPID gradually decreased from (94.15±3.84)% in the first week to (92.15±3.24)% in the fifth week. From the third week to the fifth week, the γ passing rates of In vivo EPID were significantly different from those in the first week ( t = 2.48, 2.75, 3.09, P < 0.05). Conclusions:The setup errors within 3 mm do not affect the γ passing rate of in vivo dose verification. The clinically acceptable threshold for the γ passing rate of in vivo EPID needs to be further determined. In addition, in vivo dose verification can support the clinical application of adaptive radiotherapy to a certain extent.

Effects of simulated gas of warm pressure charge explosion on neurobehavior and hippocampal neurogenesis in rats / 中华行为医学与脑科学杂志

Objective:To investigate the effects of thermobaric charge explosion simulated gas on long-term neurobehavior and hippocampal neurogenesis in rats.Methods:A total of 48 male SPF grade SD rats aged 8-10 weeks were randomly divided into control group, 5 min exposure group, 10 min exposure group and 15 min exposure group, with 12 rats in each group. Twenty-eight days after inhalation of infection, the anxiety-like behavior of rats was evaluated by an elevated cross maze, and the learning and memory function of rats was evaluated by two-way active avoidance experiment. The number of positive cells of rat hippocampal dentate gyrus neural stem cells marker molecule neural epithelial cell protein (SOX2) and mature neuron marker molecular neuronal nuclei (NeuN) was detected by immunofluorescence staining. Western blot was used to detect SOX2 and NeuN protein expression in the hippocampal tissues of rats. GraphPad prism 8.0 software was used for data analysis.The comparison of repeated measurement design data was carried out by repeated measurement ANOVA.One-way ANOVA was used for inter group comparisons, and Tukey test was used for pairwise comparison. Hippocampal nerve cells were counted using the Image J software.Results:(1) The experimental results of the elevated cross maze showed that the percentage of arm opening and the percentage of open arm residence time in each group had significant group effects ( F=22.31, 5.43, all P<0.05). The percentage of open arm entry times of rats in the 5 min, 10 min and 15 min exposure group ((28.85±1.47)%, (15.04±4.69)%, (12.66±2.89)%) and the percentage of residence time in open arm ((12.12±2.64)%, (12.16±1.11)%, (8.73±3.52)%) were all lower than those of the control group ((65.40±1.86)%, (42.92±3.12)%) (all P<0.05). There were no statistically significant differences in pairwise comparison among the three exposure groups (all P>0.05). (2)During the memory acquisition period, the results of repeated-ANOVA showed that the time main effect ( F=56.46), the group main effect ( F=16.64) and the interaction effect had significant differences( F=4.21)(all P<0. 05). The difference values of active avoidance number between the 4th day and 1st day among the four groups were significant different ( F=68.63, P<0.05). During the memory reproduction period, there were significant differences in active avoidance number and active avoidance time among the four groups ( F=8.17, 8.28, both P<0.05). The active avoidance numbers in 10 min and 15 min exposure groups((2.50±0.26) times, (2.33±0.06) times)were significantly lower than those in the control group ((8.33±3.72) times) (both P<0.05), and the active avoidance time ((6.25±0.40)s, (6.61±1.63)s) were significantly higher than those in the control group((3.69±1.41)s) (both P<0.05). The active avoidance numbers in 10 min and 15 min exposure groups were significantly lower than that in 5 min exposure group (both P<0.05). (3) The results of immunofluorescence staining showed that the numbers of SOX2-positive cells in the four groups were statistically significant ( F=5.33, P<0.05). The SOX2-positive cells in 15 min exposure group (4.33±1.12) was significantly lower than that in control group (7.67±1.52) ( P<0.05). The numbers of NeuN-positive cells in the four groups were significantly different ( F=11.06, P<0.05), and the NeuN-positive cells in the 10 min and 15 min exposure groups((105.67±8.50), (88.33±9.50)) were significantly lower than that in the control group (127.00±6.56) ( P<0.05). The NeuN-positive cells in 15 min exposure group were significantly lower than that in 5 min exposure group (110.67±8.32) ( P<0.05). (4) Western blot results showed that the relative expression of SOX2 and NeuN proteins in the four groups was statistically significant ( F=11.560, 7.035, both P<0.05). The relative expression of SOX2 and NeuN proteins in the 15 min exposure group were significantly lower than those in control group (both P<0.05). The relative expression of SOX2 protein in 15 min exposure group was significantly lower than that in 5 min exposure group ( P<0.05). Conclusion:Acute exposure to warm pressure charge explosion simulated gas can lead to anxiety-like behavior, learning and memory deficits in rats, and significantly reduce the protein expression levels of hippocampal dentate gyrus neural stem cells and mature neuronal marker molecules SOX2 and NeuN.

Efficacy of lenalidomide in treatment of multiple myeloma and its effect on levels of regulatory T cells and natural killer cells of patients / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy of lenalidomide combined with bortezomib and dexamethasone (RVd) regimen in treatment of newly diagnosed multiple myeloma (NDMM) patients and its effect on the levels of regulatory T cells (Treg cells) and natural killer (NK) cells.Methods:Thirty-eight NDMM patients who were admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2019 to May 2022 were selected for a prospective study, and were divided into control group (18 cases) and observation group (20 cases) according to random number table method. The control group was treated with bortezomib+epirubicin+dexamethasone (VAd) regimen, and the observation group was treated with RVd regimen. The efficacy and safety were compared between the two groups. The levels of Treg cells (CD4 + CD25 + FOXP3 +) and NK cells (CD3 - CD56 + CD16 +) before and after treatment in the two groups were detected by flow cytometry, and the results were compared. Results:After 4 courses of treatment, the objective response rate (ORR) of the observation group was 95.0% (19/20), which was higher than that of the control group [77.8% (14/18)], and the difference was statistically significant ( P = 0.016). Before treatment, there was no statistical difference in the levels of Treg cells and NK cells between the two groups ( P values were 0.381 and 0.650). After treatment, the level of Treg cells in the control group increased from (1.5±0.5)% before treatment to (4.7±1.3)% ( P = 0.008), while the level of Treg cells in the observation group increased from (1.4±0.5)% before treatment to (6.8±1.5)% ( P = 0.001), and the level in the observation group was higher than that in the control group ( P = 0.027); the level of NK cells in the control group increased from (16±6)% before treatment to (20±5)% ( P = 0.004), while the level of NK cells in the observation group increased from (16±6)% before treatment to (24±6)% ( P = 0.006), and the level in the observation group was higher than that in the control group ( P = 0.032). The incidence rates of thrombocytopenia and neutropenia in the observation group were higher than those in the control group, and the differences were statistically significant ( P values were 0.012 and 0.027), which was reversible after active treatment. There was no statistical difference in the incidence rates of other adverse reactions (all P>0.05). Conclusions:RVd regimen for NDMM is clinically effective, safe and reliable, and the patients' levels of Treg cells and NK cells elevate after treatment.

The past, present and future of tuberculosis treatment / 浙江大学学报·医学版

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.

Loss-of-function CFTR p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis / 亚洲男科学杂志(英文版)

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.

The Structure and Function of the Bunyavirus Nucleoprotein / 中国生物化学与分子生物学报

Bunyavirus is widely distributed, highly contagious, and has a high fatality rate. It is a negative- strand RNA virus that has a major impact on public health around the world. The development of vaccines and the search for drugs are the key to prevent bunyavirus infection. The nucleoprotein (NP) of viruses is necessary for the synthesis of viral RNA, which combines with viral RNA to form the nucleocapsid, participates in viral assembly and RNA transcription, and plays an important role in viral proliferation. In addition, NP also has B cell and T cell epitopes, which can induce cellular and humoral immunity, so NP is an ideal target for vaccine design and drug development. Given its abundance and specificity, NP is also commonly used in the detection of viral diseases. More and more bunyavirus NP structures and structures of NP-RNA complexes have been resolved. Researchers have discovered two important antiviral targets through these structures, the terminal arm and the RNA binding cleft. This paper reviews the function and three-dimensional structure of the bunyavirus NP and the research progress of NP as an antiviral target, in order to provide a theoretical basis for the prevention and treatment of the bunyavirus disease.

Effect of microRNA-138 regulation of Wnt pathway on the biological behavior of human glioma cells in vitro / 解剖学报

Objective To investigate the effect of microRNA (miR)-138 regulation of Wnt signaling pathway on the biological behavior of human glioma cells in vitro. Methods Glioma cell lines U-87MG and U251 were selected and randomly divided into blank group, miR-NC group, miR-138 mimics group and miR-138 inhibitor group. Real-time PCR was used to detect the miR-138 expression in each group; MTT, flow cytometry, Transwell assay and scratch assay were used to detect proliferation, apoptosis, invasion and migration ability of each group respectively, and Western blotting was used to detect Wnt pathway-related protein expression in each group. Results The miR-138 expression level was higher in the miR-138 mimics group compared with the remaining 3 groups, and that in the miR-138 inhibitor group was lower than that in the blank group and the miR-NC group (P<0. 05) ; Compared with the blank group, the cell proliferation rate was lower in the miR-138 mimics group and higher in the miR-138 inhibitor group, and was time-dependent (P<0. 05) ; The apoptosis rate in the miR-138 mimics group was higher than that in the blank group, miR-NC group, and miR-138 inhibitor group, while the apoptosis rate in the miR-138 inhibitor group was lower than that in the rest other groups (P<0. 05) ; The number of cell-invading cells in the miR-138 mimics group was lower than that in the blank group, miR-NC group, and miR-138 inhibitor group, while all miR-138 inhibitor group were higher than the remaining three groups (P<0. 05) ; The cell migration rate of miR-138 mimics group was lower than that of blank group, miR-NC group and miR-138 inhibitor group, while all miR-138 inhibitor group were higher than the remaining three groups (P<0. 05) ; Wnt3a, Wntl, glycogen synthase kinase 3(3(GSK-3(3) and (3-catenin protein expression in the miR-138 mimics group was lower than that in the blank group, miR-NC group, and miR-138 inhibitor group; While miR-138 inhibitor groups were higher than the remaining three groups(P<0. 05). Conclusion MiR-138 overexpression effectively inhibite the proliferation, invasion and migration of glioma cells and promote their apoptosis, probably achieved by pathway inhibition of the Wnt signaling pathway.

Resveratrol pretreatment alleviates NLRP3 inflammasomemediated cardiomyocyte pyroptosis by targeting TLR4/MyD88/ NF-κB signaling cascade in coronary microembolization-induced myocardial damage

Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague–Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosisrelated molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB.

Research progress of exosome delivery vehicles in tumor phototherapy / 药学学报

Exosome is a self-secreted phospholipid bilayer nanovesicles, and has shown great potential in drug delivery field due to the important advantages of low immunogenicity and homologous targeting. Phototherapy, mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT), utilize light to activate photoactive drug for tumor cell killing. The advanced therapeutic strategy shows low toxic side-effect and non-invasion precise advantages, and thus has made great progress in tumor treatment over the past few years. Therefore, using exosomes as a drug delivery system to deliver phototherapeutic agents can improve therapeutic performances with a reduced side-effect, and further enhance their application potential for clinical tumor therapy. This review focus on the rising cross-subjects field involving exosomes and phototherapy, and mainly introduce the research progress and relative case of exosomes-based delivery system for cancer phototherapy. Additionally, the advantages and challenges of exosome-based phototherapy are also discussed and proposed.

Recent advances in small molecule inhibitors of interleukin‑1 receptor-associated kinase / 药学学报

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

Recent advances in chemical fluorescent probes sensitive to tumor microenvironments / 药学学报

Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

Efficacy analysis of simultaneous integrated boost intensity-modulated radiotherapy combined with chemotherapy in treatment of superior mediastinal lymph node metastasis after esophageal cancer surgery / 肿瘤研究与临床

Objective:To investigate the efficacy and adverse reactions of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with chemotherapy in the treatment of superior mediastinal lymph node metastasis after esophageal cancer surgery.Methods:The clinical data of 72 patients with concurrent chemoradiotherapy for superior mediastinal lymph node metastasis after esophageal cancer surgery in Tai'an Cancer Prevention and Treatment Hospital from January 2019 to May 2021 were retrospectively analyzed, and they were divided into intensity-modulated radiotherapy (IMRT) group (36 cases) and SIB-IMRT group (36 cases) according to different radiotherapy methods. The short-term efficacy, long-term survival rate and adverse reactions of the two groups were compared.Results:The response rate in the IMRT group was 66.7% (24/36), the response rate in the SIB-IMRT group was 86.1% (31/36), and the difference between the two groups was statistically significant ( χ2 = 3.77, P = 0.047). The 1-, 2- and 3-year overall survival rates in the IMRT group were 75.0%, 44.4% and 27.8%, and the 1-, 2- and 3-year overall survival rates in the SIB-IMRT group were 83.3%, 52.8% and 33.3%; the difference in the overall survival between the two groups was not statistically significant ( χ2 = 0.70, P = 0.401). There were statistical differences in the incidence of leukopenia, radiation esophagitis and radiation pleural gastritis between the two groups (all P < 0.05). There were no statistical differences in the incidence of radiation pneumonia and gastrointestinal reactions between the two groups (both P > 0.05). Conclusions:SIB-IMRT combined with chemotherapy in patients with superior mediastinal lymph node metastasis after esophageal cancer surgery has good local control rate and mild adverse reactions.

Clinical application and pharmacokinetic study of nanocarriers in drug delivery system / 药学学报

Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.

Therapeutic Effect and Mechanism of Regulating Inflammasome NLRP3 Signaling Pathway of Lycopi Herba Extract on Chronic Prostatitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Lycopi Herba extract on chronic prostatitis （CNP） and explore the underlying action mechanism via the inflammasome NOD-like receptor protein 3 （NLRP3） pathway. MethodNormal human prostatic stromal cells， namely WPMY-1 were induced by lipopolysaccharide （LPS） of 5 mg·L-1， and the effects of Lycopi Herba extract of 3.125， 6.25， 12.5， 25， 50， and 100 mg·L-1 on interleukin-6 （IL-6） level released by LPS-induced WPMY-1 cells were detected by enzyme-linked immunosorbent assay （ELISA）. The half-maximal inhibitory concentration （IC50） was calculated. The expression of key proteins in the NLRP3 pathway was detected by western blot after Lycopi Herba extract of 50， 75， and 100 mg·L-1 was administered to WPMY-1 cells. The rat model of CNP was established by injecting carrageenan salt solution into the abdominal lobe of the prostate gland. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the prostate gland in rats. The prostate organ index of rats was measured. The level of 5α-dihydrotestosterone （5α-DHT） in serum， as well as the levels of IL-6， tumor necrosis factor-α （TNF-α）， transforming growth factor-β1 （TGF-β1）， cyclooxygenase-2 （COX-2）， prostaglandin E2 （PGE2）， and inducible nitric oxide synthase （iNOS） in prostate tissue were detected by ELISA. The key protein expressions of COX-2， TGF-β1， and NLRP3 pathway in prostate tissue were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expressions of COX-2， IL-1β， TGF-β1， and TNF-α mRNA in prostate tissue. ResultCompared with the normal group， the level of IL-6 and the protein expression levels of NLRP3， ASC， Caspase-1， and IL-1β of WPMY-1 cells in the model group were increased （P<0.05， P<0.01）. Compared with the model group， Lycopi Herba extract could inhibit the levels of IL-6 （P<0.01） released by LPS-induced WPMY-1 cells， with IC50 of 38.26 mg·L-1. The protein expression levels of NLRP3， ASC， and IL-1β in the low-， medium-， and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. The expression levels of Caspase-1 protein in medium- and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. Compared with the sham operation group， the prostate organ index of rats in the model group was significantly increased （P<0.01）， a large number of inflammatory cells were infiltrated in the prostate tissue， and the histopathological score was significantly increased （P<0.05）； the levels of 5α-DHT in serum， the levels of TNF-α， PGE2， IL-6， TGF-β1， NOS2/iNOS， and COX-2 in prostate tissue， and expression levels of COX-2， IL-1β， and TGF-β1 were significantly increased （P<0.05， P<0.01）. The mRNA expression levels of COX-2， TGF-β1， NLRP3， Caspase-1， ASC， and IL-1β in prostate tissue were significantly up-regulated （P<0.05， P<0.01）. Compared with model group， the low and high doses of Lycopi Herba extract could alleviate the pathological changes in prostate tissue induced by carrageenan， significantly reduce the level of 5α-DHT in serum， levels of TNF-α， PGE2， TGF-β1， and iNOS in prostate tissue （P<0.05， P<0.01）， and mRNA expression levels of COX-2， IL-1β， and TGF-β1 （P<0.05， P<0.01）. The protein expression levels of COX-2， Caspase-1， ASC， and NLRP3 in prostate tissue were significantly down-regulated （P<0.05， P<0.01）. The prostate organ index of the low-dose group of Lycopi Herba extract was significantly decreased （P<0.01）. The level of COX-2 in prostate tissue of the high-dose group of Lycopi Herba extract was significantly decreased， and the protein expression levels of TGF-β1 and IL-1β were significantly down-regulated （P<0.05）. ConclusionLycopi Herba extract has an obvious therapeutic effect on CNP and may reduce inflammation by inhibiting the activation of the inflammasome NLRP3 signaling pathway.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).@*METHODS@#This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.@*RESULTS@#The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.@*CONCLUSIONS@#TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).

Research progress on the association between violet light and myopia / 中国学校卫生

Abstract@#Myopia has become a major global public health problem. Exposure to outdoor light may explain the protective effect of outdoor activities on myopia. Currently, a growing number of studies focus on the effects of the spectrum on eye health. Recent studies have found that violet light may have a protective effect on myopia, but the mechanism of action between violet light and myopia is not yet fully understood. The paper reviews the association between violet light and myopia prevention and control, and the possible mechanisms of violet light and myopia to provide a reference value for further exploration of the role of violet light on myo pia .