Mechanism of Fructus Lycii against dry eye: an analysis based on network pharmacology and experimental verification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the mechanism of fructus lycii in treating dry eye based on network pharmacology and experimental verification.METHODS: Taking “fructus lycii” as key words, the active ingredients and target of fructus lycii were searched by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Gene targets related to dry eye(DE)were searched by GeneCards and OMIM databases. The target genes of fructus lycii and DE were imported into Venn software to obtain the intersection target map of them. After that, the data were imported into the String database to obtain the PPI protein-protein interaction network diagram. Using Cytoscape3.7.2 software, the PPI protein-protein interaction network diagram was constructed for active ingredients, target sites and related diseases of fructus lycii. The Bioconductor platform and R language were used for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. And the key targets in the pathogenesis of DE were verified by experiments.RESULTS: Through TCMSP, 45 types of effective chemical components of fructus lycii, 174 target genes corresponding to active components and 131 common target genes with DE were screenedout. In accordance with the network topology of “drug-composition-disease-target”, 27 main effective components of fructus lycii were found in the treatment of DE. The PPI network was analyzed according to the high degree value, which is the key targets of fructus lycii for DE treatment, mainly including AKT1, VEGFA, CASP3, IL1B, JUN, PTGS2, CXCL8, etc. According to GO enrichment analysis, 166 biological functions and processes of fructus lycii for DE treatment were obtained. KEGG enrichment analysis showed that 31 signaling pathways were involved. Additionally, experimental verification displayed that the protein expressions of AKT1, interleukin-6(IL-6), tumor necrosis factor(TNF-α)and IL-17 in conjunctiva tissue of the DE model group were significantly increased.CONCLUSIONS: Through network pharmacology, this study confirmed that the treatment of DE by fructus lycii is a complex process involving multi-components, multi-targets and multi-pathways, and that the treatment of DE by fructus lycii is mainly regulated by anti-inflammatory and apoptosis-related molecules.

Experimental study of transplantation of human umbilical cord mesenchymal stem cells in the treatment of alkali-burned cornea / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficacy of transplantation of human umbilical cord mesenchymal stem cells(hUCMSCs)in the treatment of corneal alkali burn in rabbits, and study the infiltration of polymorphonuclear neutrophils(PMNs)and the changes of vascular endothelial growth factor(VEGF)expression.METHODS: Corneal alkali burn models were established in right eyes of 75 healthy Japanese white rabbits, which were divided into three groups(group A, B and C), with 25 rabbits in each group. Group A was treated with amniotic membrane combined with hUCMSCs on the day after corneal alkali burn. Group B was treated with amniotic membrane only. Group C did not give any treatment after corneal alkali burn. At 3, 7, 14, 21 and 28d after corneal alkali burn, the corneal recovery was observed by slit lamp and photographed, the growth of corneal neovascularization(CNV)was scored, and corneal tissue was separated to make pathological sections. PMNs infiltration was observed by hematoxylin-eosin(HE)staining, and the expression of VEGF was determined by immunohistochemical staining.RESULTS: The growth of CNV in group A was much slower than that in group B at 14d after alkali burn. The CNV growth score around lesions of group A was significantly lower than that of group B(P<0.05). The quantity of PMNs increased on the 3d with the stromal layer of cornea infiltrated, relatively decreased on the 7d, shown a peak on the 14d, and then decreased gradually. Early infiltration after alkali burn was in the corneal stroma of the lesion area, and the extent of infiltration was equal to the ulcer area at later stage. The cell densities of corneal PMNs in group A and group B were significantly lower than those in group C at all time points after alkali burns(P<0.05), and those in group A were significantly lower than group B at 14 and 21d(P<0.05). The expression levels of corneal VEGF in all groups after alkali burn reached peak at 7～14d and decreased significantly at 28d, and the expression levels of VEGF in group A and group B at all time points after alkali burn were significantly lower than those in group C(P<0.05), and group A was significantly lower than that in group B at 7, 14 and 21d(P<0.05).CONCLUSION: The transplantation of hUCMSCs after alkali burn cornea can reduce the formation of CNV and inhibit corneal revascularization after alkali burn. The corneal pathological lesions and vascularization are closely related to PMNs and VEGF.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Harm Avoidance is Correlated with the Reward System in Adult Patients with Attention Deficit Hyperactivity Disorder: A Functional Magnetic Resonance Imaging Study

Objective@#Hypoactivity in the reward system among patients with attention deficit hyperactivity disorder (ADHD) is a well-known phenomenon. Whether the activity in the reward pathway is related to harm avoidance, such as in sensitivity to punishment, is unclear. Evidence regarding the potential difference between ADHD patients and controls in terms of this association is scarce. @*Methods@#Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa gambling test. Fourteen adults with ADHD and 14 controls were enrolled in the study. @*Results@#Harm avoidance was found to be positively correlated with the activities of the bilateral orbitofrontal cortex and right insula in individuals with ADHD. A group difference was also confirmed. @*Conclusion@#Understanding the roles of harm avoidance and brain activation during risk tasks is important.

A prospective study on the development and application verification of the quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology / 中华烧伤杂志

Objective: To develop a quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology, and to verify its accuracy and feasibility in clinical application. Methods: The method of prospective observational study was adopted. From April 2019 to January 2022, 59 patients with pathological scars (totally 107 scars) who met the inclusion criteria were admitted to the First Medical Center of Chinese PLA General Hospital, including 27 males and 32 females, aged 33 (26, 44) years. Based on photo modeling technology, a software for measuring three-dimensional morphological parameters of pathological scars was developed with functions of collecting patients' basic information, and scar photography, three-dimensional reconstruction, browsing the models, and generating reports. This software and the clinical routine methods (vernier calipers, color Doppler ultrasonic diagnostic equipment, and elastomeric impression water injection method measurement) were used to measure the longest length, maximum thickness, and volume of scars, respectively. For scars with successful modelling, the number, distribution of scars, number of patients, and the longest length, maximum thickness, and volume of scars measured by both the software and clinical routine methods were collected. For scars with failed modelling, the number, distribution, type of scars, and the number of patients were collected. The correlation and consistency of the software and clinical routine methods in measuring the longest length, maximum thickness, and volume of scars were analyzed by unital linear regression analysis and the Bland-Altman method, respectively, and the intraclass correlation coefficients (ICCs), mean absolute error (MAE), and mean absolute percentage error (MAPE) were calculated. Results: A total of 102 scars from 54 patients were successfully modeled, which located in the chest (43 scars), in the shoulder and back (27 scars), in the limb (12 scars), in the face and neck (9 scars), in the auricle (6 scars), and in the abdomen (5 scars). The longest length, maximum thickness, and volume measured by the software and clinical routine methods were 3.61 (2.13, 5.19) and 3.53 (2.02, 5.11) cm, 0.45 (0.28, 0.70) and 0.43 (0.24, 0.72) cm, 1.17 (0.43, 3.57) and 0.96 (0.36, 3.26) mL. The 5 hypertrophic scars and auricular keloids from 5 patients were unsuccessfully modeled. The longest length, maximum thickness, and volume measured by the software and clinical routine methods showed obvious linear correlation (with r values of 0.985, 0.917, and 0.998, P<0.05). The ICCs of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.993, 0.958, and 0.999 (with 95% confidence intervals of 0.989-0.995, 0.938-0.971, and 0.998-0.999, respectively). The longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods had good consistency. The Bland-Altman method showed that 3.92% (4/102), 7.84% (8/102), and 8.82% (9/102) of the scars with the longest length, maximum thickness, and volume respectively were outside the 95% consistency limit. Within the 95% consistency limit, 2.04% (2/98) scars had the longest length error of more than 0.5 cm, 1.06% (1/94) scars had the maximum thickness error of more than 0.2 cm, and 2.15% (2/93) scars had the volume error of more than 0.5 mL. The MAE and MAPE of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.21 cm, 0.10 cm, 0.24 mL, and 5.75%, 21.21%, 24.80%, respectively. Conclusions: The quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology can realize the three-dimensional modeling and measurement of morphological parameters of most pathological scars. Its measurement results were in good consistency with those of clinical routine methods, and the errors were acceptable in clinic. This software can be used as an auxiliary method for clinical diagnosis and treatment of pathological scars.

Clinical outcome of surgical resection for multifocal T2-T3 hepatocellular carcinoma up to 3 nodules: a comparative analysis with a single nodule

Background/Aims@#Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases. @*Methods@#Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated. @*Results@#All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038). @*Conclusions@#Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules.

Considerations on investigation on quality standard of Chinese patent medicine / 药学学报

Chinese patent medicine (CPM) is an important part of traditional and Chinese medicine (TCM). Its quality has direct impact on the safety and effectiveness of clinical use. The quality standard is the pivotal approach to guarantee the quality of CPM. Due to the complex material basis, multitudinous quality influencing factors and unveiled active ingredients, dose-effect relationship and action mechanism, the investigation on quality standard faces many difficulties. This paper surveys the current quality status of CPM and the general situation of CPM standards. At present, the dosing problem has the crucial impact on the quality of CPM. The current quality standard system of CPM is confirmed and the limitations are indicated. Based on the above analysis, the principles and considerations on investigation of quality standard are proposed as follows: ① Adhere to safety as the bottom line, strengthen the risk-control ability of the standard of CPM; ② Adhere to theory of TCM and comprehensive quality, improve the integrative control level of the CPM standard; ③ Emphasize technological development and innovation, promote the quality control competence of CPM standard; ④ Facilitate planning and coordination, optimize the management of the CPM standard system; ⑤ Reinforce investigation on evaluation method, develop grade evaluation standard, accelerate high-quality development of CPM. Finally, the future perspective on investigation of CPM quality standard is prospected.

Clinical Characteristics and Obstetric Outcomes of Pregnant Women Who Underwent Surgery for Adnexal Torsion / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical characteristics and obstetric outcomes of pregnant women who underwent surgery for adnexal torsion at different gestational weeks. MethodsA retrospective study was done on 39 women who underwent surgery for adnexal torsion during pregnancy in the First Affiliated Hospital， Sun Yat-sen University between March 2013 and March 2023， with 18 cases in 1st trimester （<14 weeks）， 11 in 2nd trimester （14-27+6 weeks） and 10 in 3rd trimester （≥28 weeks）. The clinical characteristics， treatment and obstetric outcomes were compared among the three groups. ResultsThe 1st trimester group had higher proportion of assisted reproductive technology （ART） use than the 2nd and 3rd trimester groups （P=0.026）. There was no significant difference in the clinical manifestations， including abdominal pain， nausea， vomiting and fever among the three groups， while elevated white blood cells （WBC） counts was more commonly seen in the 2nd and 3rd trimester groups. Adnexal masses <5 cm in diameter occurred in 0， 18.2%， and 10.0% of cases in 1st， 2nd and 3rd trimester groups respectively （P=0.014）. No statistical significance was found in the location of twisted adnexa， number of circles or pathological nature. The 1st trimester group had a higher sensitivity of ultrasound in the diagnosis of adnexal torsion compared with the 2nd and 3rd trimester groups （77.8%， 36.4%， 20.0%； P=0.008）. More laparoscopic surgery were performed in the 1st trimester group than the other two groups （55.6% ， 27.3%， 0.0%； P=0.008）. There was no significant difference in gestational week of delivery， delivery mode， newborn gender， neonatal birth weight and follow-up of newborns among the three groups. The 3rd trimester group showed a higher risk of preterm delivery （P=0.050）. ConclusionsDuring the 1st trimester of pregnancy， adnexal torsion is more common in patients using ART and ultrasound plays a crucial role in the diagnosis. During the 2nd and 3rd trimester， adnexal torsion should be suspected in patients with abdominal pain and elevated WBC but no aspetic inflammation. Laparoscopic surgery is safe for adnexal torsion during pregnancy and can achieve a favorable maternal and neonatal outcome.

Retrograde thoracic duct approach via left venous angle in the treatment of chylothorax / 中华放射学杂志

Objective:To investigate the feasibility and effect of retrograde thoracic duct approach via left venous angle in the treatment of chylothorax.Methods:From July 2019 to April 2021, the clinical data of 16 patients with chylothorax in Shanghai Pulmonary Hospital Tongji University were retrospectively collected. All patients underwent percutaneous inguinal lymphography, super selective retrograde thoracic duct catheterization was attempted via the left venous angle. Successful patients underwent direct thoracic ductography. After the position of the rupture was shown, the thoracic duct was embolized with microcoils and glue.Results:The inguinal lymphography of 16 patients was successful, and the end of thoracic ducts was identified. Retrograde thoracic duct catheterizations were successful in 10 patients, 6 cases showed contrast agent overflow in thoracic ductography, and the thoracic ducts were embolized using microcoils combined with glue. Chylothorax was improved in 16 patients, and 6 cases were completely cured. All patients had no serious complications.Conclusion:It is an effective and feasible method to treat chylothorax by retrograde thoracic ductography and embolization approach via left venous angle.

Polysaccharide Krestin Prevents Alzheimer's Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-β Processing / 神经科学通报·英文版

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.

Value of central vein sign and iron deposition to differentiate multiple sclerosis from neuromyelitis optica spectrum disorder / 中华放射学杂志

Objective:To investigate the value of central vein sign (CVS) and iron deposition on quantitative susceptibility imaging (QSM) of 3.0 T MRI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disease (NMOSD).Methods:This study was a retrospective study. A total of 54 MS patients and 49 NMOSD patients were enrolled from July 2018 to December 2020 in People′s Hospital of Leshan and the First Affiliated Hospital of Chongqing Medical University. All patients underwent conventional MRI and three-dimensional enhanced T 2*-weighted angiography (3D-ESWAN), and ESWAN-filtered phase and QSM were reconstructed from 3D-ESWAN data. First, brain lesions of MS and NMOSD were screened on proton density (PD)-T 2WI, and then the location of lesions, CVS and nodular/annular iron deposition were observed on phase and QSM images. The χ 2 test was used to compare the differences in intracranial lesion location, CVS and iron deposition between MS and NMOSD patients. Receiver operating characteristic curve and area under the curve (AUC) were used to assess the efficiency of CVS and QSM iron deposition to differentiate MS from NMOSD. Results:A total of 968 MS lesions were observed in 54 MS patients, of which CVSs were found in 354 lesions and 227 CVSs were located around the lateral ventricles, 117 in deep white matter (DWM) and 10 in the cortex/subcortex; 372 lesions showed nodular iron deposition, and 193 lesions ring iron deposition on QSM. Totally 247 brain lesions were observed in 41 of 48 patients with NMOSD, of which CVSs were found in 4 lesions and 1 located around the lateral ventricle, 3 located in the DWM; 3 lesions showed nodular iron deposition on QSM. There were significant differences in cortex/subcortex lesions, CVS and iron deposition between MS and NMOSD patients (χ 2 were 29.33, 115.66 and 258.21, respectively, all P<0.001). The AUC of CVS for differentiating MS from NMOSD was 0.941 (95%CI 0.887-0.994), with a sensitivity of 96.3% and a specificity of 91.8%; the AUC of iron deposition for differentiating MS from NMOSD was 0.969 (95%CI 0.930-1.000), with a sensitivity of 100% and a specificity of 93.9%. Conclusion:CVS and iron deposition on 3.0 T MRI are distinct radiologic features of MS lesions from those of NMOSD lesions, and have certain value in the differential diagnosis.

Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To detect whether Danlou Tablet (DLT) regulates the hypoxia-induced factor (HIF)-1α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia (CIH)-induced dyslipidemia and arteriosclerosis.@*METHODS@#The mature adipocytes were obtained from 3T3-L1 cell culturation and allocated into 8 groups including control groups (Groups 1 and 5, 0.1 mL of cell culture grade water); DLT groups (Groups 2 and 6, 0.1 mL of 1,000 µg/mL DLT submicron powder solution); dimethyloxalylglycine (DMOG) groups (Groups 3 and 7, DMOG and 0.1 mL of cell culture grade water); DMOG plus DLT groups (Groups 4 and 8, DMOG and 0.1 mL of 1,000 µg/mL DLT submicron powder solution). Groups 1-4 used mature adipocytes and groups 5-8 used HIF-1 α-siRNA lentivirus-transfected mature adipocytes. After 24-h treatment, real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1 α and Angptl4. In animal experiments, the CIH model in ApoE-/- mice was established. Sixteen mice were complete randomly divided into 4 groups including sham group, CIH model group [intermittent hypoxia and normal saline (2 mL/time) gavage once a day]; Angptl4 Ab group [intermittent hypoxia and Angptl4 antibody (30 mg/kg) intraperitoneally injected every week]; DLT group [intermittent hypoxia and DLT (250 mg/kg) once a day], 4 mice in each group. After 4-week treatment, enzyme linked immunosorbent assay was used to detect the expression levels of serum total cholesterol (TC) and triglyceride (TG). Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques.@*RESULTS@#Angptl4 expression was dependent on HIF-1 α, with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α -transfected cells. DLT inhibited HIF-1 α and Angptl4 mRNA expression (P<0.05 or P<0.01) and reduced HIF-1 α and Angptl4 protein expressions with DMOG in mature adipocytes (all P<0.01), as the effect on HIF-1 α protein also existed in the presence of siHIF-1 α (P<0.01). ApoE-/- mice treated with CIH had increased TG and TC levels (all P<0.01) and atherosclerotic plaque. Angptl4 antibody and DLT both reduce TG and TC levels (all P<0.01), as well as reducing atherosclerotic plaque areas, narrowing arterial wall thickness and alleviating atherosclerotic lesion symptoms to some extent.@*CONCLUSION@#DLT had positive effects in improving dyslipidemia and arteriosclerosis by inhibiting Angptl4 protein level through HIF-1 α-Angptl4 mRNA signaling pathway.

Effects of NLRP3-mediated pyroptosis on olfaction dysfunction in allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.

Generation of Highly Expandable Intestinal Spheroids Composed of Stem Cells

Many of early findings regarding intestinal stem cells (ISCs) and their niche in the human intestine have relied on colorectal cancer cell lines and labor-intensive and time-consuming mouse models. However, these models cannot accurately recapitulate the physiologically relevant aspects of human ISCs. In this study, we demonstrate a reliable and robust culture method for 3D expanding intestinal spheroids (InSexp ) mainly comprising ISCs and progenitors, which can be derived from 3D human intestinal organoids (HIOs). We did functional chararcterization of InSexp derived from 3D HIOs, differentiated from human pluripotent stem cells, and optimization culture methods. Our results indicate that InSexp can be rapidly expanded and easily passaged, and show enhanced growth rates via WNT pathway activation. InSexp are capable of exponential cell expansion and cryopreservation. Furthermore, in vitro-matured HIO-derived InSexp proliferate faster than immature HIO-derived InSexp with preservation of the parental HIO characteristics. These findings may facilitate the development of scalable culture systems for the long-term maintenance of human ISCs and provide an alternative platform for studying ISC biology.

Neuropathologic damage induced by radiofrequency ablation at different temperatures

Abstract Objective To explore the molecular mechanism of neuropathologic damage induced by radiofrequency ablation at different temperatures. Methods This is basic research, and 36 SD rats were used to construct the neuropathological injury model. The rats were subjected to radiofrequency stimulation at different temperatures and were divided into 6 groups according to the temperature injury: 42°, 47°, 52°, 57°, 62°, and 67°C groups. Conduction time, conduction distance, and nerve conduction velocity were recorded after temperature injury. HE-staining was used to observe the histopathological morphology of the sciatic nerve. The expression of SCN9A, SCN3B, and NFASC protein in sciatic nerve tissue were detected by western blot. Results With the increase in temperature, nerve conduction velocity gradually decreased, and neurons were damaged when the temperature was 67°C. HE-staining showed that the degrees of degeneration of neurons in rats at 47°, 52°, 57°, 62°, and 67°C were gradually increased. The expression of SCN9A, SCN3B protein in 57°, 62°, 67°C groups were much higher than that of NC, 42°, 47°, 52°C groups. However, the expression of NFASC protein in 57°, 62°, 67°C groups was much lower than that of the NC, 42°, 47°, 52°C groups. Conclusion There was a positive correlation between temperature caused by the radiofrequency stimulation to neuropathological damage. The mechanism is closely related to the expression of SCN9A, SCN3B, and NFASC protein in nerve tissue caused by heat transfer injury.

Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro / 中国中药杂志

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP)

Background/Aims@#Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. @*Methods@#Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. @*Results@#Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. @*Conclusions@#The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Clinical efficacy of sticking-needle acupuncture plus tendon-regulating manipulation in the treatment of acute ankle sprain / 针灸推拿医学（英文版）

Objective: To explore the treatment effect of sticking-needle acupuncture plus tendon-regulating manipulation on pain, swelling and joint dysfunction due to acute ankle sprain.Methods: A total of 80 patients with acute ankle sprain were recruited and divided into a control group and a treatment group according to the random number table method, with 40 patients in each group. Both groups received the same conventional interventions. The control group was treated with additional tendon-regulating manipulation, and the treatment group was treated with tendon-regulating manipulation plus sticking-needle acupuncture. The pain, swelling and joint dysfunction of the ankle were observed in both groups before and after 3 d, 7 d and 14 d of treatment. Results: Before treatment, there was no statistically significant difference in the visual analog scale (VAS) score of pain between the two groups (P>0.05). After treatment, the VAS scores of both groups showed a decreasing trend over time, and the differences within the groups were statistically significant (P<0.05). After 3 d, 7 d and 14 d of treatment, the VAS scores in the treatment group were lower than those in the control group, with statistically significant differences (P<0.05). Before treatment, there was no statistically significant difference in the degree of swelling between the two groups (P>0.05). After treatment, the degrees of swelling in both groups showed a decreasing trend over time, and the differences within the groups were statistically significant (P<0.05). After 3 d and 7 d of treatment, the degrees of swelling in the treatment group were lower than those in the control group, with statistically significant differences (P<0.05). There was no statistical difference in the degree of swelling between the two groups after 14 d of treatment (P>0.05). Before treatment, there was no statistically significant difference in the American Orthopedic Foot Ankle Society (AOFAS) ankle-hindfoot scale score between the two groups (P>0.05). After treatment, the AOFAS ankle-hindfoot scale scores of both groups showed an increasing trend over time, and all the differences within the groups were statistically significant (P<0.05). After 3 d, 7 d and 14 d of treatment, the AOFAS ankle-hindfoot scale scores in the treatment group were higher than those in the control group, with statistically significant differences (P<0.05). Conclusion: Based on the routine intervention, the addition of sticking-needle acupuncture and tendon-regulating manipulation was better in alleviating pain and swelling and improving joint function in patients with acute ankle sprain than the addition of tendon-regulating manipulation alone.

Anti-cancer Mechanism of "Clematis Radix et Rhizoma-Trichosanthis Radix" Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the potential targets and mechanism of action of "Clematis Radix et Rhizoma-Trichosanthis Radix" based on network pharmacology. Method:Chinese Medicine System Pharmacology Analysis Platform（TCMSP） was used to screen out active ingredients and corresponding target proteins of Clematis Radix et Rhizoma and Trichosanthis Radix according to oral bioavailability（OB） and drug likeness（DL），cancer disease targets were screened out using GeneCards and OMIM databases，R language software was used to screen out common targets of clematis，trichosanthin and cancer diseases， Cytoscape 3.7.2 software was used to construct a network map of "drug-active ingredient-disease-target"， STRING database was used to draw protein protein interaction（PPI）of common target proteins， R language software was used to perform enrichment analysis of gene ontology（GO） functions and Kyoto encyclopedia of genes and genomes（KEGG） channels on effective targets. Result:A total of 9 effective active ingredients were obtained from Clematis Radix et Rhizoma-Trichosanthis Radix powder pair. A total of 31 target genes were searched，and 814 relevant target genes were searched from cancer diseases. The two kinds of relevant target genes were matched to obtain 9 common target genes，which mainly involved endopeptidase，cysteine-type endopeptidase activities involving in the apoptosis process and cancer necrosis factor receptor superfamily binding and other biological processes，and played a role in the treatment of cancers by regulating apoptosis，measles，hepatitis B，kaposi sarcoma-associated herpesvirus infection，p53，interleukin-17（IL-17），tumor necrosis factor（TNF） and many other pathways. Conclusion:The mechanism of Clematis Radix et Rhizoma-Trichosanthis Radix in the treatment of cancer is preliminarily studied. Clematis Radix et Rhizoma-Trichosanthis Radix has multiple active ingredients and can play a role in treating cancer through multiple targets and multiple pathways.