Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Better timing for HoLEP: a retrospective analysis of patients treated with HoLEP over a 10-year period with a 1-year follow-up / 亚洲男科学杂志(英文版)

The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People's Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8-18) and Group B (IPSS of 19-35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.

Hepatitis B virus X protein promotes podocyte pyroptosis in hepatitis B virus-associated glomerulonephritis by down-regulating microRNA -223 targeting NLRP3 inflammasome / 中华肝脏病杂志

Objective: To investigate the potential function and related mechanism of microRNA-223 (miRNA-223) in the podocyte pyroptosis of hepatitis B virus (HBV)-associated glomerulonephritis induced by HBV X protein (HBx). Methods: HBx-overexpressing lentivirus was transfected into human renal podocytes to mimic the pathogenesis of HBV-GN. Real-time fluorescence quantitative PCR and Western blotting experiments were used to detect the mRNA and protein expression of pyroptosis-related proteins [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1], and inflammatory factors (interleukin-1β and interleukin-18), respectively.TUNEL staining and flow cytometry were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression of podocytes biomarkers desmin and nephrin; Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to measure caspase-1 activity. The dual luciferase reporter gene assay was used to verify the downstream target of miRNA-223. Podocytes were divided into the following nine groups: control group (no special treatment), empty plasmid group (transfected with empty plasmid), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+miRNA-223 mimic group (transfected with HBx overexpression lentivirus and miRNA-223 mimic), HBx overexpression+miRNA-223 inhibitor group (transfected with HBx overexpression lentivirus and miRNA-223 inhibitor), HBx overexpression+miRNA-223 mimic+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 mimic+ NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 siRNA), HBx overexpression+miRNA-223 inhibitor+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 inhibitor+NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 siRNA). Results: miRNA-223 was down-regulated in HBx overexpression group compared with the control group (P < 0.05). TUNEL and immunofluorescence staining showed that NLRP3 knockdown attenuated podocyte injury and pyroptosis induced by HBx overexpression (P < 0.05). Dual luciferase reporter gene assay demonstrated that NLRP3 was one of the downstream targets of miRNA-223. Rescue experiments revealed that NLRP3 overexpression weakened the protective effect of miRNA-223 in podocyte injury (P < 0.05). The addition of miRNA-223 mimic and NLRP3 siRNA decreased the expression of NLRP3 inflammasome and cytokines, and reduced the number of pyroptosis cells induced by HBx overexpression (all P < 0.05); The addition of miRNA-223 inhibitor and NLRP3 overexpression plasmid significantly increased the expression of NLRP3 inflammasome and cytokines, caspase-1 activity, and the number of pyroptosis cells (all P < 0.05). Conclusion: HBx may promote podocyte pyroptosis of HBV-GN via downregulating miRNA-223 targeting NLRP3 inflammasome, suggesting that miRNA-223 is expected to be a potential target for the treatment of HBV-GN.

Application of the CBL combined with TBL based on SP teaching method in clinical teaching of department of intensive care medicine / 中华医学教育探索杂志

Objective:To study the teaching effect of the teaching method of case-based learning (CBL) combined with team-based learning (TBL) based on the standard patient (SP) in the clinical teaching of department of intensive care medicine.Methods:A total of 60 medical students clinically studying in the department of intensive care medicine were randomly divided into 2 groups, with 30 students in each group. The two groups received the clinical teaching through the lecture-based learning (LBL) teaching method and the CBL combined with TBL based on SP teaching method respectively. By evaluating the clinical synthesis ability of the students of two groups and the satisfaction survey of the two teaching methods, the teaching effect was evaluated. SPSS 19.0 statistical software was used to perform Chi-square test and t-test. Results:Compared with LBL teaching method, the students who accepted the CBL combined with TBL based on SP teaching method had significantly better clinical comprehensive ability ( P < 0.05), mainly in their clinical thinking ability [(4.18±0.55) vs. (3.66±0.47)], clinical skills [(4.03±0.61) vs. (3.59±0.52)] and communication ability with patients [(4.11±0.58) vs. (3.74±0.50)]. In addition, student satisfaction with teaching methods was also higher ( P <0.05), especially in the satisfaction of learning interest [(4.38 ± 0.72) vs. (3.65±0.56)], self-learning ability [(4.24±0.71) vs. (3.91±0.52)], clinical thinking ability [(4.09±0.66) vs. (3.22±0.54)], communication ability [(4.42±0.60) vs. (3.67±0.48)], and team cooperation spirit [(4.15±0.58) vs. (3.78±0.51)]. Conclusion:The teaching method of CBL combined with TBL based on SP is feasible and has good teaching effect in the clinical teaching of department of intensive care medicine.

Association Between Daily Executive Function and Core Symptoms， Attention Deficit-Hyperactivity Symptoms in Children with Autism Spectrum Disorder / 中山大学学报(医学科学版)

ObjectiveTo explore the association between daily executive function and core symptoms， the symptoms of attention deficit hyperactivity disorder （ADHD） in children with autism spectrum disorder （ASD）， and the moderating effect of theory of mind and other cognitive abilities on this association. MethodsChildren aged 6-12 years with ASD were recruited， and 86 children were identified according to the inclusion and exclusion criteria. Wechsler Intelligence Test for Children， Fourth Edition （WISC-Ⅳ）， Strange Story Test （SST） and Behavior Rating Inventory of Executive Function （BRIEF） were used to evaluate children's cognitive ability. Swanson Nolan and Pelham-Version Ⅳ Scale （SNAP-Ⅳ）， Social Responsiveness Scale （SRS）， and Repetitive Behavior Scale-Revise （RBS-R） were used to assess the severity of ADHD symptoms， social impairment， and repetitive stereotyped behavior. Multiple linear regression was used to explore the association between daily executive function and ADHD symptoms， social impairment， repetitive stereotyped behaviors. ResultsAfter controlling for the score of strange stories， verbal comprehension index （VCI） and other factors， the full scale score and each index of BRIEF were positively correlated with full scale score of SNAP （b = 0.619-0.741， b’ = 0.637-0.755）， SRS （b = 0.928-1.200， b’ = 0.417-0.513） and RBS-R （b = 0.326-0.525， b’ = 0.339-0.520） in children with ASD （P< 0.05）， and the SNAP total score was more strongly correlated with the full scale BRIEF score and each index score （b’ = 0.637-0.755，P< 0.01）. In addition to daily executive function， strange stories score （b = -2.218- -1.839） and age （b = 3.181-4.037） were also the important factors affecting the social function of children with ASD （P< 0.01）. There were no moderating effects of strange stories score and age on the association between BRIEF score and full scale score of SNAP， SRS， and RBS-R（P> 0.05）. ConclusionThe deficits of daily executive function in school-aged ASD children are significantly associated with core symptoms and ADHD symptoms， and the association is independent of other cognitive domains， such as theory of mind and verbal comprehension intelligence quotient.

Construction of Literature Knowledge Ontology for Traditional Chinese Medicine Clinical Trials： A Review / 中国实验方剂学杂志

ObjectiveTo effectively organize the interdisciplinary knowledge of traditional Chinese medicine （TCM） and evidence-based medicine contained in the clinical trial literature of TCM and facilitate the processing and mapping of multi-source data， this paper organized the knowledge of clinical trial literature of TCM by ontology modeling. MethodThe seven-step method and skeleton method were used to develop the ontology. After the structure and language characteristics of TCM clinical trial literature were analyzed， the ontological and non-ontological resources such as top-level framework of Scientific Evidence and Provenance Information Ontology （SEPIO） and TCM language system （TCMLS） were reused to determine the domain concepts and attribute relationship. Finally， the core concepts and attribute relationship such as disease， syndrome， symptom， grouping， intervention measures， outcome indicators and literature quality information were determined. ResultThe information contained in the clinical trial literature of TCM was divided into five categories. According to the Cochrane risk of bias assessment tool and CONSORT 2010 statement， the literature quality evaluation information was mapped to the ontology， and a total of 68 categories， 8 object attributes， and 38 data attributes were established， which basically realized the structured expression of clinical trial literature. ConclusionThe ontology of TCM clinical trial literature constructed in this study can well organize， utilize， and present the construction and association of internal knowledge system in TCM clinical trial literature， underpinning the reasoning of strength of evidence and information of diagnosis and treatment in the future.

Agreement of corneal high-order aberrations measured by three wavefront aberrometers in myopic adults / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the agreement of corneal high-order aberrations from Topcon KR-1W, i.Profiler and OPD-Scan Ⅲ wavefront aberrometers in myopic adults.METHODS:A prospective clinical study. A total of 92 adult patients(92 eyes)with myopia in the department of optometry, the People's Hospital of Guangxi Zhuang Autonomous Region from June to August 2022 were enrolled. The third-order and fourth-order corneal aberrations at the pupil diameter of 4 and 6mm were measured by Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, respectively. The difference and agreement of the three aberrometers were evaluated.RESULTS: The measurements at 6mm pupil diameter were all greater than those at 4mm pupil diameter. Although there were no statistical differences in the measurements of Z-44、Z-24 by the three aberrometers at 4 pupil diameter(P&#x003E;0.05), there were statistical differences in other measurements(P&#x003C;0.05). The aberration results measured by the three aberrometers were statistically different at the 6mm pupil diameter(P&#x003C;0.05). The 95% limit of agreement(95%LoA)of the measurements of higher-order aberration, including the third-order aberrations at 4mm pupil diameter and the third-order and fourth-order aberrations at 6mm pupil diameter(except for the Z-24)were greater than 0.1μm. The concordance correlation coefficient(Pc)was lower than 0.90, indicating a poor consistency. The correlation coefficients of corneal higher-order aberrations were significantly different among the three aberrometers at 4 and 6mm pupil diameter(r4mm=0.215～0.805, P4mm&#x003C;0.05; r6mm=0.561～0.916, P6mm&#x003C;0.001).CONCLUSION:There were significant differences in the measurements of the third- and fourth-order corneal aberrations at 4 and 6mm pupil diameter among Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, and the agreements were poor, so they are not interchangeably in clinical applications.

Pathogenesis and surgical outcomes of different types of myopic traction maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the pathogenesis and surgical outcomes of different types of myopic traction maculopathy(MTM)using optical coherence tomography(OCT).METHODS: A total of 193 patients(210 eyes)with MTM were retrospectively included, of which 74 eyes(35.2%)underwent vitrectomy combined with internal limiting membrane(ILM)peeling. The patients were categorized into three groups: foveal detachment(FD), foveoschisis(FS)and lamellar macular hole(LMH). Based on the central foveal thickness(CFT)at baseline(M0), eyes with FD were classified into two subgroups: extensive FD and limited FD. Outcomes included best-corrected visual acuity(BCVA), CFT, posterior staphyloma height(PSH), the presence of epiretinal membrane(ERM)and ILM detachment. Risk factors for BCVA at 6mo after vitrectomy(M6)were analyzed using linear regression.RESULTS: At M0, ERM was highly present in eyes with LMH(rs=0.28, P&#x003C;0.001). Eyes with FD and FS were characterized by higher incidence of ILM detachment(rs=-0.25, P&#x003C;0.001). After vitrectomy, CFT and BCVA significantly improved in all eyes(P&#x003C;0.001). Eyes with extensive FD were characterized by a thicker CFT(rs=0.56, P&#x003C;0.001), a lower incidence of ILM detachment(rs=-0.25, P=0.034)and a thicker nasal PSH(rs=0.27, P=0.024)than eyes with limited FD. Eyes with extensive FD were associated with a worse BCVA at M0(P=0.013)and M6(P=0.030)than eyes with limited FD. Extensive FD(β=-0.295, P=0.042)and BCVA at M0(β=0.669, P&#x003C;0.001)were risk factors for a worse BCVA at M6.CONCLUSION: There are several pathogenetic mechanisms in MTM. ILM detachment may exert a dominant role in the development of FD and FS, while ERM may have a role in LMH. Vitrectomy combined with ILM peeling improved functional and anatomical outcomes in MTM patients. Eyes with extensive FD may carry a poor prognosis.

Buzhong Yiqitang Reduces CIH-induced Pulmonary Inflammatory Injury by ACE2-Ang（1-7）-Mas Axis / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Buzhong Yiqitang （BZYQT） on pulmonary inflammation in mice induced by chronic intermittent hypoxia （CIH） and preliminarily elucidate its mechanism. MethodForty healthy male C57BL/6 mice aged 6-8 weeks were randomly divided into the following groups： normoxia group， model group （exposed to CIH）， and low-， medium-， and high-dose BZYQT groups. The normoxia group was exposed to a normoxic environment， while the model group and the low-， medium-， and high-dose BZYQT groups were exposed to intermittent hypoxia. In the BZYQT groups， the BZYQT （8.1， 16.2， 32.4 g·kg-1·d-1） was administered orally 30 min before placing the mice in the hypoxic chamber， while the model group and the normoxia group received an equivalent volume of normal saline. After five weeks of modeling， pulmonary function of the mice was measured using an EMKA animal lung function analyzer， and lung tissue samples were collected after the pulmonary function tests. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the lung tissue of each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α） in the serum， as well as angiotensin Ⅱ （Ang Ⅱ） and angiotensin-（1-7） ［Ang（1-7）］ in lung tissue. Western blot and immunohistochemistry were used to detect the protein expression of IL-6， IL-8， TNF-α， angiotensin-converting enzyme 2 （ACE2）， and mitochondrial assembly receptor （Mas）. ResultCompared with the normoxia group， the model group showed significant abnormalities in lung function （P<0.05， P<0.01）， lung tissue changes， such as thickening of alveolar walls and inflammatory cell infiltration， increased levels of IL-6， IL-8， TNF-α in the serum and Ang Ⅱ in lung tissue （P<0.01）， decreased level of Ang（1-7） （P<0.01）， increased protein expression of IL-6， IL-8， and TNF-α， and decreased protein expression of ACE2 and Mas （P<0.05， P<0.01）. Compared with the model group， the BZYQT groups showed improvement in lung function （P<0.05， P<0.01）， and HE staining of lung tissue showed approximately normal alveolar wall thickness and reduced inflammatory cell infiltration. Immunohistochemistry and Western blot analysis showed a significant decrease in the expression of inflammatory-related proteins （P<0.05， P<0.01）， and a significant increase in ACE2 and Mas protein expression （P<0.05， P<0.01）. ConclusionBZYQT can improve lung injury in mice exposed to CIH by regulating the ACE2-Ang（1-7）-Mas axis to inhibit inflammatory responses.

The research status and development trends of brain-computer interfaces in medicine / 生物医学工程学杂志

Brain-computer interfaces (BCIs) have become one of the cutting-edge technologies in the world, and have been mainly applicated in medicine. In this article, we sorted out the development history and important scenarios of BCIs in medical application, analyzed the research progress, technology development, clinical transformation and product market through qualitative and quantitative analysis, and looked forward to the future trends. The results showed that the research hotspots included the processing and interpretation of electroencephalogram (EEG) signals, the development and application of machine learning algorithms, and the detection and treatment of neurological diseases. The technological key points included hardware development such as new electrodes, software development such as algorithms for EEG signal processing, and various medical applications such as rehabilitation and training in stroke patients. Currently, several invasive and non-invasive BCIs are in research. The R&D level of BCIs in China and the United State is leading the world, and have approved a number of non-invasive BCIs. In the future, BCIs will be applied to a wider range of medical fields. Related products will develop shift from a single mode to a combined mode. EEG signal acquisition devices will be miniaturized and wireless. The information flow and interaction between brain and machine will give birth to brain-machine fusion intelligence. Last but not least, the safety and ethical issues of BCIs will be taken seriously, and the relevant regulations and standards will be further improved.

CRP is an important factor affecting the timing of surgical drainage of ureteral calculi with upper urinary tract infection / 现代泌尿外科杂志

【Objective】 To explore the timing of surgical drainage for ureteral calculi with upper urinary tract infection. 【Methods】 Clinical data of 117 cases of ureteral calculi with upper urinary tract infection treated in our hospital during Jan.2018 and Jan.2020 were retrospectively analyzed. According to different treatment methods, the patients were divided into surgical drainage group and non-surgical drainage group. The patients’ age, gender, side of calculi, peak body temperature, time of onset, white blood cell (WBC) count, C-reactive protein (CRP) and other clinical indicators were compared between the two groups. The cutoff value of surgical drainage was determined with receiver operator characteristic (ROC) curve. 【Results】 The patients’ age, peak body temperature, WBC count and CRP level were the influencing factors of surgical drainage (P<0.05). Regression analysis showed that CRP (P<0.001), age (P=0.003) and WBC count (P=0.014) were independent risk factors for surgical drainage. The area under the ROC curve (AUC) of CRP, age, and WBC count were 0.923, 0.601, and 0.796, respectively. The cutoff value of CRP was 29.87 mg/L (sensitivity 79.4%, specificity 90.0%). Logistic regression model showed CRP was a significant clinical predictor. 【Conclusion】 Ureteral calculi with upper urinary tract infection need to be diagnosed and treated in time. Positive anti-infection should be performed during emergency treatment, and surgical drainage could be selected according to the value of CRP.

Transvesical robot-assisted radical prostatectomy: a report of 13 cases / 现代泌尿外科杂志

【Objective】 To share the technical key points and experience of transvesical robot-assisted radical prostatectomy (TvRARP). 【Methods】 The clinical data of 13 patients with prostate cancer (PCa) receiving TvRARP during Nov.2021 and May 2022 were collected. The operation time, estimated blood loss, blood transfusion rate, catheter removal time, postoperative length of hospital stay, immediate urinary continence rate, postoperative IIEF-5 score and perioperative complications were evaluated. 【Results】 The operation time was (142±39) min, estimated intraoperative blood loss was (76±40) mL, and no transfusion was needed. The median postoperative IIEF-5 score was 16 (12-22), hospital stay 3 (2-5)days, and catheter removal time 7(5-14)days. Of all 13 patients, 12(92.3%) achieved immediate urinary continence at the removal of catheter. There were no postoperative complications of Clavien Ⅲ and above. Clavien Ⅰ-Ⅱ complications were observed in 4 patients (30.8%). 【Conclusion】 TvRARP is feasible and safe for selected patients with clinically localized PCa, which can ensure promising postoperative urinary continence and preserve erectile functional.

Three new anthraquinones from Prismatomeris tetrandra (Roxb.) K. Schum and their protective effects in neuroblastoma cells / 药学学报

Three new anthraquinones were isolated from the 80% ethanol extract of Prismatomeris tetrandra by silica gel, MCI, ODS column chromatography and high performance preparative liquid chromatography (HPLC). The structures of the new compounds were identified by mass spectrometry, nuclear magnetic resonance and other spectroscopic methods as 6-hydroxy-1,2,3-trimethoxy-7-methylanthracene-9,10-dione (1), 6-(hydroxymethyl)-1,2,3-trimethoxyanthracene-9,10-dione (2) and 7-hydroxy-6-(hydroxymethyl)-1,2-dimethoxyanthracene-9,10-dione (3). Compounds 1, 2 and 3 showed protective effects against monosodium glutamate-induced damage in SH-SY5Y neuroblastoma cells, with the cell survival rates elevated 18.45%, 4.31%, and 7.65%, respectively.

Study on Mechanism of Action of Matrine in Treatment of Inflammatory Bowel Disease Based on Zebrafish Model and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo study the mechanism of matrine in the treatment of inflammatory bowel disease （IBD） based on the zebrafish model and network pharmacology. MethodThe IBD model of zebrafish was established using 2，4，6-trinitro-benzenesulfonicacid （TNBS）， and the intestinal phagocytic function， goblet cell secretion， and neutrophil aggregation were evaluated using neutral red staining， alcian blue staining， and neutrophil number changes. Changes in tumor necrosis factor （TNF）-α and cholecystokinin （CCK） content in zebrafish were determined by using relevant reagent kits. Network pharmacology and molecular docking techniques were used to predict the potential mechanism of matrine in the treatment of IBD. Gene expression of relevant targets was verified through Real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the model group， the matrine administration group can increase the neutral red staining area in a dose-dependent manner and improve intestinal phagocytic function（P<0.05，P<0.01）. It can reduce the staining area of alcian blue and affect the secretion of intestinal goblet cells（P<0.01）. It can reduce the number of neutrophil granulocytes， relieve its aggregation， significantly reduce TNF-α content（P<0.01）， and increase the CCK content. Network pharmacology analysis identifies 28 potential targets for matrine in the treatment of IBD. The top five targets by protein-protein interaction （PPI） network analysis are CHRNA7， DRD1， CHRNA4， SLC6A3， and GRM5. The Kyoto encyclopedia of genes and genomes （KEGG） results show that the treatment of IBD with matrine may be related to neuroactive ligand-receptor interaction， cholinergic synapse， and neutrophil extracellular trap formation. Real-time PCR results show that matrine can affect the expression level of related target genes. Conclusionmatrine has a certain therapeutic effect on IBD and can affect the inflammatory response of IBD. Its therapeutic effect may be related to neuroactive ligand-receptor interaction and other pathways.

Effectiveness of HPV vaccines in real-world study / 中华微生物学和免疫学杂志

Human papillomavirus (HPV) is an epitheliotropic virus. High-risk HPV infections lead to precancerous lesions which may progress to cancer in the cervix, vagina and vulva, while low-risk HPV infections cause benign lesions such as genital warts and recurrent respiratory papillomas. HPV infection remains one of the major public health problems threatening human health. To date, six prophylactic preventive HPV vaccines have been licensed, and the effectiveness of HPV vaccination has gradually appeared in some countries with earlier vaccination. HPV vaccination has been proved to be effective in protecting against diseases related to HPV infection, which leads to significant reductions in the incidence of vaccine-type HPV-related infection, high cervical lesions, anogenital warts, recurrent respiratory papillomatosis and other relevant diseases. The herd protection effect of the vaccines is outstanding. Meanwhile, a bivalent HPV vaccine has been demonstrated for the cross-protection against HPV infections of non-vaccine types (HPV31/33/45) in real-world vaccination practice.

Antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby isolates from clinical patients and food sources in Hangzhou / 中华微生物学和免疫学杂志

Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.

Clinicopathological analysis of superior mediastinal lymph node metastases in medullary thyroid carcinoma / 中华肿瘤杂志

Objective: To investigate the clinicopathological characteristics of superior mediastinal lymph node metastases (sMLNM) in medullary thyroid carcinoma (MTC). Methods: This retrospective analysis enrolled the patients who were treated for sMLNM of MTC in our hospital from May 2012 to January 2021. All patients were suspected of sMLNM due to preoperative imaging. According to the pathological results, the patients were divided into two groups named sMLNM group and the negative superior-mediastinal-lymph-node group. We collected and analyzed the clinical features, pathological features, pre- and post-operative calcitonin (Ctn), and carcinoembryonic antigen (CEA) levels of the two groups. Logistic regression analysis was used to analyze risk factors, and receiver operation characteristic (ROC) curves were drawn to determine the optimal cut-off values of preoperative Ctn and preoperative CEA for predicting sMLNM. Results: Among the 94 patients, 69 cases were in the sMLNM group and 25 cases were in the non-SMLNM group. Preoperative Ctn level (P=0.003), preoperative CEA level (P=0.010), distant metastasis (P=0.022), extracapsular lymph node invasion (P=0.013), the number of central lymph node metastases (P=0.002) were related to sMLNM, but the multivariate analysis did not find any independent risk factors. The optimal threshold for predicting sMLNM by pre-operative Ctn is 1500 pg/ml and AUC is 0.759 (95% CI: 0.646, 0.872). The sensitivity, specificity, positive predictive value, and negative predictive value of diagnosis are 61.2%, 77.3%, 89.1%, 39.5%, respectively. In patients who underwent mediastinal lymph node dissection through transsternal approach, the metastatic possibility of different levels from high to low were level 2R (82.3%, 28/34), level 2L (58.8%, 20/34), level 4R (58.8%, 20/34), level 3 (23.5%, 8/34), level 4L (11.8%, 4/34). Postoperative complications occurred in 41 cases (43.6%), and there was no perioperative death in all cases. 14.8% (12/81) of the patients achieved biochemical complete response (Ctn≤12 pg/ml) one month after surgery, 5 of these patients were in sMLNM group. Conclusions: For patients who have highly suspicious sMLNM through imaging, combining with preoperative Ctn diagnosis can improve the accuracy of diagnosis, especially for patients with preoperative Ctn over 1 500 pg/ml. The superior mediastinal lymph node dissection for the primary sternotomy should include at least the superior mediastinal levels 2-4 to avoid residual lesions. The strategy of surgery needs to be cautiously performed. Although the probability of biochemical cure in sMLNM cases is low, nearly 40% of patients can still benefit from the operation at the biochemical level.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.