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.

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.

Occupational exposure level and requirements for radiation protection of nuclear medical staff / 中华劳动卫生职业病杂志

With the rapid development of nuclear medicine, the number of nuclear medical staff has increased a lot in the past few years in China. Close-range operations, such as preparation and injections of radiopharmaceuticals, are usually carried out in nuclear medicine department. And the use of unsealed radionuclides may also create internal exposure risk. So, occupational exposure of nuclear medical staff is a main issue of occupational health management in China. In this paper, the occupational exposure level and requirements for radiation protection of nuclear medical staff are introduced to provide references for the related work that radiological health technical institutions carry out.

Using machine learning algorithm to predict the risk of post-traumatic stress disorder among firefighters in Changsha / 中南大学学报(医学版)

OBJECTIVES@#Firefighters are prone to suffer from psychological trauma and post-traumatic stress disorder (PTSD) in the workplace, and have a poor prognosis after PTSD. Reliable models for predicting PTSD allow for effective identification and intervention for patients with early PTSD. By collecting the psychological traits, psychological states and work situations of firefighters, this study aims to develop a machine learning algorithm with the aim of effectively and accurately identifying the onset of PTSD in firefighters, as well as detecting some important predictors of PTSD onset.@*METHODS@#This study conducted a cross-sectional survey through convenient sampling of firefighters from 20 fire brigades in Changsha, which were evenly distributed across 6 districts and Changsha County, with a total of 628 firefighters. We used the synthetic minority oversampling technique (SMOTE) to process data sets and used grid search to finish the parameter tuning. The predictive capability of several commonly used machine learning models was compared by 5-fold cross-validation and using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, precision, recall, and F1 score.@*RESULTS@#The random forest model achieved good performance in predicting PTSD with an average AUC score at 0.790. The mean accuracy of the model was 90.1%, with an F1 score of 0.945. The three most important predictors were perseverance, forced thinking, and reflective deep thinking, with weights of 0.165, 0.158, and 0.152, respectively. The next most important predictors were employment time, psychological power, and optimism.@*CONCLUSIONS@#PTSD onset prediction model for Changsha firefighters constructed by random forest has strong predictive ability, and both psychological characteristics and work situation can be used as predictors of PTSD onset risk for firefighters. In the next step of the study, validation using other large datasets is needed to ensure that the predictive models can be used in clinical setting.

Research advances on the mechanism of non-coding RNA regulated diabetic wound healing / 中华烧伤杂志

Diabetic wounds are a common complication of diabetic patients, and the incidence has been increasing in recent years. In addition, its poor clinical prognosis seriously affects the quality of life of patients, which has become the focus and difficulty of diabetes treatment. As the RNA regulating gene expression, non-coding RNA can regulate the pathophysiological process of diseases, and play an important role in the healing process of diabetic wounds. In this paper, we reviewed the regulatory role, diagnostic value, and therapeutic potential of three common non-coding RNA in diabetic wounds, in order to provide a new solution for the diagnosis and treatment of diabetic wounds at the genetic and molecular level.

Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears / 中华烧伤杂志

Objective: To investigate the influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears, and to analyze the related mechanism. Methods: Experimental research methods were adopted. The complete fat pads on the back of 42 male New Zealand white rabbits aged 2 to 3 months were cut to prepare adipose stem cell matrix gel, and a full-thickness skin defect wound was established on the ventral side of each ear of each rabbit. The left ear wounds were included in adipose stem cell matrix gel group (hereinafter referred to as matrix gel group), and the right ear wounds were included in phosphate buffer solution (PBS) group, which were injected with autologous adipose stem cell matrix gel and PBS, respectively. The wound healing rate was calculated on post injury day (PID) 7, 14, and 21, and the Vancouver scar scale (VSS) scoring of scar tissue formed on the wound (hereinafter referred to as scar tissue) was performed in post wound healing month (PWHM) 1, 2, 3, and 4. Hematoxylin-eosin staining was performed to observe and measure the histopathological changes of wound on PID 7, 14, and 21 and the dermal thickness of scar tissue in PWHM 1, 2, 3, and 4. Masson staining was performed to observe the collagen distribution in wound tissue on PID 7, 14, and 21 and scar tissue in PWHM 1, 2, 3, and 4, and the collagen volume fraction (CVF) was calculated. The microvessel count (MVC) in wound tissue on PID 7, 14, and 21 and the expressions of transforming growth factor β1 (TGF-β1) and α smooth muscle actin (α-SMA) in scar tissue in PWHM 1, 2, 3, and 4 were detected by immunohistochemical method, and the correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group was analyzed. The expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in wound tissue were detected by enzyme-linked immunosorbent assay on PID 7, 14, and 21. The number of samples at each time point in each group was 6. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, paired sample t test, least significant difference test, and Pearson correlation analysis. Results: On PID 7, the wound healing rate in matrix gel group was (10.3±1.7)%, which was close to (8.5±2.1)% in PBS group (P>0.05). On PID 14 and 21, the wound healing rates in matrix gel group were (75.5±7.0)% and (98.7±0.8)%, respectively, which were significantly higher than (52.7±6.7)% and (90.5±1.7)% in PBS group (with t values of 5.79 and 10.37, respectively, P<0.05). In PWHM 1, 2, 3, and 4, the VSS score of scar tissue in matrix gel group was significantly lower than that in PBS group (with t values of -5.00, -2.86, -3.31, and -4.45, respectively, P<0.05). Compared with the previous time point within the group, the VSS score of scar tissue at each time point after wound healing in the two groups was significantly increased (P<0.05), except for PWHM 4 in matrix gel group (P>0.05). On PID 7, the granulation tissue regeneration and epithelialization degree of the wounds between the two groups were similar. On PID 14 and 21, the numbers of fibroblasts, capillaries, and epithelial cell layers in wound tissue of matrix gel group were significantly more than those in PBS group. In PWHM 1, 2, 3, and 4, the dermal thickness of scar tissue in matrix gel group was significantly thinner than that in PBS group (with t values of -4.08, -5.52, -6.18, and -6.30, respectively, P<0.05). Compared with the previous time point within the group, the dermal thickness of scar tissue in the two groups thickened significantly at each time point after wound healing (P<0.05). Compared with those in PBS group, the collagen distribution in wound tissue in matrix gel group was more regular and the CVF was significantly increased on PID 14 and 21 (with t values of 3.98 and 3.19, respectively, P<0.05), and the collagen distribution in scar tissue was also more regular in PWHM 1, 2, 3, and 4, but the CVF was significantly decreased (with t values of -7.38, -4.20, -4.10, and -4.65, respectively, P<0.05). Compared with the previous time point within the group, the CVFs in wound tissue at each time point after injury and scar tissue at each time point after wound healing in the two groups were significantly increased (P<0.05), except for PWHM 1 in matrix gel group (P>0.05). On PID 14 and 21, the MVC in wound tissue in matrix gel group was significantly higher than that in PBS group (with t values of 4.33 and 10.10, respectively, P<0.05). Compared with the previous time point within the group, the MVC of wound at each time point after injury in the two groups was increased significantly (P<0.05), except for PID 21 in PBS group (P>0.05). In PWHM 1, 2, 3, and 4, the expressions of TGF-β1 and α-SMA in scar tissue in matrix gel group were significantly lower than those in PBS group (with t values of -2.83, -5.46, -5.61, -8.63, -10.11, -5.79, -8.08, and -11.96, respectively, P<0.05). Compared with the previous time point within the group, the expressions of TGF-β1 and α-SMA in scar tissue in the two groups were increased significantly at each time point after wound healing (P<0.05), except for the α-SMA expression in matrix gel group in PWHM 4 (P>0.05). There was a significantly positive correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group (r=0.92, P<0.05). On PID 14 and 21, the expressions of VEGF (with t values of 6.14 and 6.75, respectively, P<0.05) and EGF (with t values of 8.17 and 5.85, respectively, P<0.05) in wound tissue in matrix gel group were significantly higher than those in PBS group. Compared with the previous time point within the group, the expression of VEGF of wound at each time point after injury in the two groups was increased significantly (P<0.05), and the expression of EGF was decreased significantly (P<0.05). Conclusions: Adipose stem cell matrix gel may significantly promote the wound healing of full-thickness skin defects in rabbit ears by promoting collagen deposition and expressions of VEGF and EGF in wound tissue, and may further inhibit the scar hyperplasia after wound healing by inhibiting collagen deposition and expressions of TGF-β1 and α-SMA in scar tissue.

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.

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).

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.

Functional Autapses Form in Striatal Parvalbumin Interneurons but not Medium Spiny Projection Neurons / 神经科学通报·英文版

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr2+. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABAA receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.

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.

Effect of Alcohol Extract of Oroxylum indicum on Reducing Uric Acid and Protecting Kidney in Hyperuricemia Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum （MHD-80） on reducing uric acid （UA） and protecting the kidney in the hyperuricemia （HUA） model in vivo. MethodPotassium oxazine （350 mg·kg-1） and adenine （80 mg·kg-1） were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups， including the normal group， model group， allopurinol group （5 mg·kg-1）， febusotan group （5 mg·kg-1）， and MHD-80 low-， medium-， and high-dose groups （3， 6， 12 mg·kg-1）， with 10 in each group. Except for the normal group， the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8th to 14th day after modeling， each group was given corresponding drugs by intragastric administration， once a day. 1 h after the last administration， blood was collected from the eyeballs， and kidney and liver tissues of mice were collected. Serum levels of UA， urea nitrogen （BUN）， and creatinine （Cr） and liver activity of xanthine oxidase （XOD） were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxilin-eosin （HE） staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 （ABCG2） and glucose-facilitating transporter 9 （GLUT9） in kidney tissues were detected by Western blot. ResultIn vivo experiment shows that compared with the normal group， the serum levels of UA， Cr， BUN， inflammatory factors TNF-α， IL-1β， and liver XOD activity in the serum of mice in the model group were significantly increased （P<0.05， P<0.01）， and the expression of GLUT9 in kidney tissues was significantly up-regulated （P<0.05）. ABCG2 protein expression was significantly down-regulated （P<0.05）， and renal injury was obvious. Compared with the model group， the levels of UA， BUN， Cr， TNF-α， IL-1β， and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees （P<0.05， P<0.01）， GLUT9 protein expression was significantly down-regulated （P<0.01）， ABCG2 protein expression was significantly up-regulated （P<0.05） in the high-dose group of MHD-80， and the degree of renal injury was reduced. ConclusionMHD-80 has certain uric acid reduction， anti-inflammatory， and anti-renal injury effects， which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.

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 .

Alcohol Extract of Angelicae Pubescentis Radix Treats Gouty Arthritis Induced by MSU via NLRP3/ASC/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the efficacy and mechanism of the alcohol extract DH50 of Angelicae Pubescentis Radix in treating gouty arthritis induced by monosodium urate （MSU） crystals in vivo and in vitro. MethodFifty male SD rats were randomly assigned into five groups （n=10）： a normal group， a model group， a dexamethasone （DXMS， 0.07 mg·kg-1） group， and low- （DH50-D， 9 mg·kg-1） and high-dose （DH50-G， 18 mg·kg-1） DH50 groups. The rats in the normal group and model group were administrated with the same amount of pure water. On day 5， the gouty arthritis model was established by injecting MSU into the right ankle joint of rats. The toe volume and joint inflammation index were measured 4， 8， 24， and 48 h after modeling. The pathological changes of the synovial tissue were detected by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， and IL-6 in the synovial tissue. Western blot was employed to measure the protein levels of NOD-like receptor protein 3 （NLRP3）， cysteine-aspartic protease-1 （Caspase-1）， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， IL-1β， and cyclooxygenase-2 （COX-2） in the synovial tissue. Furthermore， the cell inflammation model was established with RAW264.7 cells stimulated with MSU （75 mg·L-1）. The cell experiments were carried out with 6 groups： a normal group， a model group， a positive drug （DXMS， 100 μmol·L-1） group， and low- （DH50-D， 25 mg·L-1）， medium- （DH50-Z， 50 mg·L-1）， and high-dose （DH50-G， 100 mg·L-1） DH50 groups. Methyl thiazolyl tetrazolium （MTT） assay was employed to determine the cell viability， ELISA to determine the content of TNF-α in the supernatant of cell culture， and Western blot to determine the protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2. ResultCompared with the normal group， the rat model group showed increased toe swelling degree and joint inflammatory index （P<0.01）， serious infiltration of the synovium， elevated levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， ASC， IL-1β， and COX-2 （P<0.05， P<0.01）. Compared with the rat model group， low- and high-dose DH50 mitigated the toe swelling degree， decreased the joint inflammatory index， alleviated the inflammatory infiltration， lowered the levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and down-regulated the expression of related proteins （P<0.05， P<0.01）. Compared with the normal group， the cell model group showed elevated level of TNF-α in the supernatant （P<0.01） and up-regulated protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2 （P<0.05）. Compared with the model group， low， medium， and high doses of DH50 lowered the level of TNF-α in the supernatant of cell culture in a dose-dependent manner and down-regulated the expression of related proteins （P<0.05， P<0.01）. ConclusionDH50 can mitigate gouty arthritis both in vitro and in vivo by inhibiting the activation of NLRP3 inflammasomes and the production of inflammatory cytokines.