Mesenchymal Stem Cells Ameliorate Fibrosis by Enhancing Autophagy via Inhibiting Galectin-3/Akt/mTOR Pathway and by Alleviating the EMT via Inhibiting Galectin-3/Akt/GSK3β/Snail Pathway in NRK-52E Fibrosis

Background and Objectives@#Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. @*Methods@#and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. @*Conclusions@#SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo explore the effect of Tangbikang granules （TBK） on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor （NF）-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin （STZ， ip） at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group， low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK groups， and lipoic acid group （0.026 8 g·kg-1） according to body weight and blood glucose level， and a normal group was designed. After modeling， administration began and lasted 12 weeks. The body mass， blood glucose level， and thermal withdrawal latency （TWL） of the rats were detected before treatment and at the 4th， 8th， and 12th week of administration. At the 12th week， the sciatic nerve was collected for hematoxylin-eosin （HE） and Luxol fast blue （LFB） staining， and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in sciatic nerve were measured by enzyme-linked immunosorbent assay （ELISA）， and the levels of AMPK， phosphorylated （p）-AMPK， and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point （P<0.01）. The levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group （P<0.01）， and the p-AMPK/AMPK ratio was smaller than that in the normal group （P<0.01）. Compared with the model group， TBK of the three doses lowered the TWL （P<0.05， P<0.01） and the levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve of rats （P<0.05， P<0.01）， and high-dose and medium-dose TBK raised p-AMPK/AMPK （P<0.05， P<0.01）. The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB， thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.

Preparation，characterization，in vitro drug release property and cytotoxicity of Periplaneta americana extract-loaded spider fibroin membrane / 中国药房

OBJECTIVE To prepare spider fibroin membrane loaded with Periplaneta americana extract， and investigate its characterization， in vitro drug release property and cytotoxicity. METHODS Using natural spider silk collected from Chilobrachys guangxiensis as raw material， P. americana extract as model drug， the drug-loaded spider fibroin membrane （hereinafter referred to as drug-loaded membrane） was prepared by solvent casting method. The material matrix spider fibroin membrane without P. americana extract （hereinafter referred to as blank membrane） was prepared with same method. The membrane structure was characterized by static water contact angle， Fourier infrared chromatography， X-ray diffraction and scanning electron microscopy from different angles； drug release characteristics in artificial saliva were simulated in vitro to evaluate the drug sustained-release performance. MTT assay was adopted to validate the cytotoxicity of drug-loaded membrane. RESULTS The drug-loaded membrane was prepared， and the static water contact angle was less than 90°， which was less than that of blank membrane. The drug-loaded membrane showed the characteristic absorption peak to polypeptide of P. americana extract at 1 500-1 700 cm－1. X-ray diffraction and scanning electron microscopy also proved that the drug was successfully loaded into the pellicle. The release time of the pellicle in artificial saliva was more than 200 min. The MTT test results showed that the cell proliferation rates of blank membrane and drug-loaded membrane were 84.6% and 79.4% （both greater than 70%）， respectively， without significant potential cytotoxicity. CONCLUSIONS Drug-loaded membrane prepared with natural spider silk has a certain sustained-release effect in artificial saliva， which can be further developed as a drug sustained-release carrier with excellent biological characteristics and biocompatibility.

Gegen Qinliantang Regulates Polarization Tendency of Macrophages to Intervene in Vulnerable Plaque in AS of ApoE-/- Mice / 中国实验方剂学杂志

ObjectiveTo explore the mechanism underlying the intervention of Gegen Qinliantang （GQL） in vulnerable plaques in atherosclerosis （AS） of ApoE-/- mice by regulating the polarization of macrophages. MethodTwelve normal C57BL/6CNC mice were used as the control group， and 60 ApoE-/- mice of the same line were randomized into 5 groups： model group， low-dose， middle-dose， and high-dose GQL groups （GQL-D， GQL-Z， and GQL-G groups， respectively）， and atorvastatin group （western medicine group）. High-fat diet was used for modeling. The control group and the model group were given （ig） equal volume of sterile distilled water， and GQL-D， GQL-Z， GQL-G， and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. The levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected with biochemical methods. The distribution of plaques in the aortic region was observed based on oil red O staining and hematoxylin-eosin （HE） staining. Serum levels of M1 pro-inflammatory factors tumor necrosis factor （TNF）-α and interleukin （IL）-6 and M2 anti-inflammatory factors IL-13 and transforming growth factor （TGF）-β were detected by enzyme-linked immunosorbent assay （ELISA）. Protein expression of macrophage mannose receptor CD206/arginase-1 （Arg-1） and CD206/inducible nitric oxide synthase （iNOS） was determined by double-labeling immunofluorescence， and mRNA expression of aortic Arg-1 and iNOS by real-time polymerase chain reaction （PCR）. ResultLevels of TG， TC， and LDL-C were significantly lower and HDL-C level was significantly higher in the GQL-Z， GQL-G， and western medicine groups than in the model group. As the concentration of GQL rose， the area with plaques gradually shrunk and the color became lighter. The staining areas of the GQL-G group and the western medicine group were the most scattered. The administration groups showed significant increase in the protein levels of Arg-1 and CD206， significant decrease in the protein level of iNOS， significant rise of Arg-1 mRNA level， and significant drop of iNOS mRNA level （P<0.05）. ConclusionGQL intervenes in the vulnerable plaques in AS by improving lipid metabolism， inhibiting macrophage M1 polarization， promoting macrophage M2 polarization， and further improving the inflammatory microenvironment.

Explore Potential Molecular Mechanism of Gegen Qinliantang in Intervention of Atherosclerosis Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveThis study aims to explore the potential molecular mechanism of Gegen Qinliantang （GQL） in the intervention of atherosclerosis （AS） based on network pharmacology and molecular docking. MethodThe active components and targets of each medicinal in GQL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and AS-related genes from 7 databases. Thereby， the anti-AS targets of GQL were screened out. Cytoscape 3.8.0 was employed to construct the "component-target" network， and STRING the protein-protein interaction （PPI） network. Core targets were screened out with CytoNCA. R clusterProfiler was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of target genes， which were then visualized. Finally， molecular docking of the top ten active components with the core targets of AS was performed and the binding affinity was compared with that between atorvastatin and the core targets. ResultIn the end， 150 active components of GQL， 20 289 AS targets， and 213 common targets were retrieved， and 48 core common targets were screened out. They were mainly involved in the GO terms of nuclear receptor activity， ligand activation， and transcription factor activity and the pathways of fluid shear force and AS， advanced glycation end products-receptor for advanced glycation end products （AGE/RAGE）， interleukin-17 （IL-17）， tumor necrosis factor （TNF）， Toll-like receptor pathways and other signaling pathways closely related to AS. The molecular docking results showed that the effective components of GQL had high binding affinity to core targets of AS， and the binding affinity was even higher than that between the atorvastatin and core targets. The five groups with high binding affinity were puerarin-TNF， baicalein-inducible nitric oxide synthase 2 （NOS2）， puerarin-NOS2， and formononetin-NOS2， wogonin-NOS2. ConclusionThe above result provides new ideas for further exploration of this classical decoction.

Application of Three Blood Stasis Models in Zebrafish in Evaluation of Anti-thrombosis and Anti-myocardial Hypoxia Activities of Notoginseng Radix et Rhizoma / 中国实验方剂学杂志

ObjectiveTo establish blood stasis models in zebrafish using three inducers and select the optimal model for evaluating the activity of Notoginseng Radix et Rhizoma in promoting blood circulation. MethodArachidonic acid （AA）， ponatinib， and isoprenaline （ISO） were used to induce blood stasis models in zebrafish. A normal group， a model group， a positive drug group， and Notoginseng Radix et Rhizoma water extract freeze-dried powder groups at different concentrations were set up. The staining intensity of cardiac erythrocytes and the fluorescence intensity of cardiac apoptotic cells were calculated， the anti-thrombotic effect and anti-myocardial hypoxia activity of Notoginseng Radix et Rhizoma were evaluated. The activities of water extract and 70% methanol extract of Notoginseng Radix et Rhizoma were compared based on the preferred AA- and ISO-induced blood stasis models in zebrafish and the difference in the chemical composition was analyzed by UHPLC LTQ-Orbitrap MS/MS. ResultAfter induction by AA and ponatinib， the staining intensity of cardiac erythrocytes was reduced （P<0.01）， and the fluorescence intensity of cardiac apoptotic cells increased after the induction by ISO （P<0.01）. The freeze-dried powder of the water extract of Notoginseng Radix et Rhizoma could antagonize the thrombosis in the AA-induced model （P<0.01） and the myocardial apoptosis in the ISO-induced model （P<0.05）， while no significant improvement in the thrombosis was observed in the ponatinib-induced model. The freeze-dried powder of 70% methanol extract of Notoginseng Radix et Rhizoma could inhibit myocardial apoptosis in the ISO-induced blood stasis model （P<0.01）， and the effect was stronger than that of the freeze-dried powder of Notoginseng Radix et Rhizoma water extract. The difference in chemical composition lay in some saponins （such as ginsenoside Re）， amino acids， and acetylenic alcohols. ConclusionAA， ponatinib， and ISO all can serve as inducers for the blood stasis model in zebrafish. AA- and ISO-induced models can be used to evaluate the activity of freeze-dried powder of Notoginseng Radix et Rhizoma water extract in promoting blood circulation. The chemical compositions of the freeze-dried powders of Notoginseng Radix et Rhizoma extracted with water and 70% methanol are quite different. For the ISO-induced blood stasis model， the freeze-dried powder of Notoginseng Radix et Rhizoma extracted with 70% methanol has a stronger ability against myocardial hypoxia. Saponins and acetylenic alcohols may be closely related to the effects of promoting blood circulation and resolving blood stasis.

Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study / 中国中药杂志

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Comprehensive evaluation system for quality of Chinese medicinal decoction pieces based on "experience-ingredients-activity-electronic sensing" / 中国中药杂志

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

Endoscopic posterior nasal neurectomy for the treatment of allergic rhinitis: anatomy and analysis of clinical efficacy / 中华耳鼻咽喉头颈外科杂志

Objective: To propose total posterior nasal neurectomy with transection of sphenopalatine neurovascular bundle from anatomy for the treatment of allergic rhinitis, and to explore its clinical application. Methods: Two fresh cadaveric heads (4 sides) were dissected through endoscopic transnasal middle meatus approach at Otorhinolaryngology Anatomy Laboratory of China-Japan Friendship Hospital. The structures of the craniofacial bone related to the surgical approach were observed. Twelve patients with allergic rhinitis who treated in Department of Otorhinolaryngology, China-Japan Friendship Hospital from Feb. 1 2019 to Jun. 10 2021 were selected. All the patients were treated by posterior nasal neurotomy with the technique of complete transection of sphenopalatine neurovascular bundle and followed up for 1 year after sugery. During the follow-up, 2 patients were lost. The other 10 patients included 4 males and 6 females, aging from 29 to 69 years. Visual Analogue Scale (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were used to evaluate the effect of the surgery. SPSS 25.0 software was used for statistical analysis. Results: Important anatomic landmarks of transnasal middle meatus approach were obtained during anatomy, such as ethmoid crest, sphenopalatine foramen/notch, palatine orbital process and sphenopalatine process. The postoperative VAS scores of nose, eye, pharynx, ear and whole body and total VAS scores were significantly lower than those before operation, with statistically significant difference (nose 2.50±1.70 vs 6.47±2.17, eyes 1.15±0.89 vs 3.60±2.57, pharynx 1.30±1.36 vs 4.25±3.64, ear 1.10±1.03 vs 2.67±2.00, whole body 1.08±1.24 vs 3.60±1.17, total 7.13±4.31 vs 20.58±9.05, all P<0.05). The postoperative RQLQ scores of sleep, nose, eyes, practical problems, emotion, activity and the total RQLQ scores of patients were significantly lower than those before operation, with statistically significant difference (sleep 0.80±0.69 vs 2.93±1.33, nose 1.38±1.18 vs 3.93±1.50, eyes 0.58±0.66 vs 1.80±1.25, practical problems 1.10±1.22 vs 3.03±1.84, emotion 1.00±1.81 vs 2.58±2.00, activity 2.77±2.93 vs 6.00±1.85, total 8.99±8.92 vs 22.42±8.69, all P<0.05). There was no significant difference in preoperative and postoperative scores of non-nasal/ocular symptoms (1.37±1.60 vs 2.16±1.12, P=0.166). There was no other complication except 2 cases with short-term postoperative numbness. Conclusions: Total posterior nasal neurectomy with transection of sphenopalatine neurovascular bundle is a safe, effective and feasible method for the treatment of intractable allergic rhinitis, and its long-term efficacy needs further observation.

Predictive model of curative effect of mite subcutaneous immunotherapy in 5-18 years of age patients with allergic asthma / 中华儿科杂志

Objective: To analyze the factors affecting the efficacy of mite subcutaneous immunotherapy (SCIT) in allergic asthma patients aged 5-18 years, and to find the best predictive model for the curative effect. Methods: The data of 688 patients aged 5-18 years with allergic asthma who completed more than 3 years of mite SCIT from December 2006 to November 2021 in the Department of Respiratory Medicine, Children's Hospital Affiliated to Nanjing Medical University were retrospectively analyzed. Male, results of skin prick test (SPT), age, daily medication score (DMS), visual analogue scale (VAS) score, and enrollment season were defined as independent variables. R language models, including Logistic regression model, random forest model and extreme gradient boosting (XGboost) model, were used to analyze the impact of these independent variables on the outcomes. The receiver operating characteristic curve was applied to compare the predictive ability of the models. Hypothesis testing of the area under curve (AUC) of the 3 models was performed using DeLong test. Results: There were 435 males and 253 females in the 688 patients. There were 349 patients aged 5-<8 years, 240 patients aged 8-<11 years, and 99 patients aged 11-18 years. SPT showed that 429 cases (62.4%) were only allergic to mite, and 259 cases (37.7%) were also allergic to other allergens. According to the efficacy after 3 years of SCIT, 351 cases (51.0%) discontinued the treatment and 337 cases (49.0%) required continued treatment. The DMS was 4 (3, 6) at initiation, 3 (2, 5) at 3 months, 3 (2, 5) at 4 months, 2 (1, 3) at 12 months, and 0 (0, 1) at 3 years of SCIT treatment. The VAS was 3.5 (2.5, 5.2) at initiation, 3.2 (2.2, 4.8) at 3 months, 2.6 (1.4, 4.1) at 4 months, 1.0 (0.6, 1.8) at 12 months, and 0.5 (0, 1.2) at 3 years of treatment. At 3, 4, and 12 months, the rate of decline in DMS was 0 (0, 20%), 16.7% (0, 33.3%), and 50.0% (31.0%, 75.0%), respectively; and the VAS decreased by 7.1% (3.2%,13.8%), 27.6% (16.7%,44.4%), and 70.2% (56.1%, 82.3%), respectively. Regarding the enrollment season, 99 cases were in spring, 230 cases in summer, 171 cases in autumn, and 188 cases in winter. The R language Logistic regression model found that DMS>3 points at 3 months (OR=-3.5, 95%CI:-4.3--2.7, P<0.01), male (OR=-1.7, 95%CI:-2.3--1.0), P<0.01), DMS decline rate>16.7% at 4 months (OR=-1.6, 95%CI:-2.3--0.8, P<0.01) and DMS decline rate>0 at 3 months (OR=-0.7, 95%CI:-1.3--0.2, P<0.05) had higher possibility of drug discontinuation; whereas, the decline rate of DMS at 12 months>50.0% (OR=0.7, 95%CI: 0.1-1.3, P<0.05), VAS at 12 months>1.0 points (OR=0.9, 95%CI: 0.3-1.6, P<0.05), and initial VAS<4.0 points (OR=1.0, 95%CI: 0.4-1.6, P<0.01) had lower possibility of drug discontinuation. Both the random forest model and the XGboost model showed that DMS>3 points at 3 months (mean decrease accuracy=30.9, importance=0.45) had the greatest impact on drug discontinuation. The AUC of the random forest model was the largest at 0.900, with an accuracy of 78.2% and a sensitivity of 84.5%. Logistic regression model had AUC of 0.891, accuracy of 80.0%, and sensitivity of 80.0%; XGboost model had AUC of 0.886, accuracy of 76.9%, and sensitivity of 84.5%. The AUC of the pairwise comparison model by DeLong test found that all three models could be used for the prediction of this data set (all P>0.05). Conclusions: The more drugs used to control the primary disease, and the more careful reduction of the control medicine after starting SCIT treatment, the more favorable it is to stop all drugs after 3 years. The random forest model is the best predictive model for the efficacy of mite SCIT in asthmatic children.

Progress in research of economic evaluation of COVID-19 vaccination strategies / 中华流行病学杂志

Objective: To understand the research progresses of economic evaluation of COVID-19 vaccination strategies both at home and abroad, and provide reference for the economic evaluation of COVID-19 vaccination strategies using real word data in China. Methods: Literature retrieval was conducted for related papers published from January, 2020 to December, 2021 in Chinese and English databases, including the economic evaluation of COVID-19 vaccination, and the results of the related literatures were narratively integrated. Results: A total of 16 English literatures (including 3 reviews) were included, and it was found that the COVID-19 vaccination was cost-effective or cost-saving regardless of the vaccine types, while the cost-effectiveness in different population and under different vaccination dose strategies varied due to vaccine efficacy, vaccine price, duration of natural immunity, duration of vaccination campaign, vaccine supply, and vaccination pace. Conclusions: China lacks suitable evidences of economic evaluation of COVID-19 vaccination strategies based on real-world data in the context of long-term epidemic. Therefore, further researches of suitable strategies of booster COVID-19 vaccination are needed.

Artificial intelligence-based literature data warehouse for vaccine safety / 中华流行病学杂志

Objective: To establish a sustainable updated literature data warehouse for global vaccine safety assessment, and provide data support for evidence-based vaccine safety assessment. Methods: Semi-automated construction and updating of a literature data warehouse were achieved through the continuous integration of standard operating steps of evidence-based reviews with artificial intelligence technologies. Following the standard procedure of a systematic literature review, the literatures about vaccine safety assessment published before November 29, 2020 were retrieved from 9 databases including OVID, Scopus, Web of Science, Cochrane Library, and ClinicalTrails.org in English and Wanfang, CNKI, VIP, and SinoMed in Chinese. Literatures were screened for two rounds in a semi-automatic manner (by artificial intelligence literature processing system and manual work) according to the inclusion/exclusion criteria. Furthermore, the literatures were classified according to the types of vaccines and adverse events. The updating strategy was established, and the literature data warehouse was updated regularly. Experts were organized to select specific vaccine safety topics and carry out special demonstration studies. Results: More than 0.41 million articles were retrieved. According to the inclusion/exclusion criteria, 23 304 articles were included after two rounds of screening. At present, we have selected and completed three prior topics as demonstration studies, including the systematic review of "DPT (diphtheria, pertussis and tetanus) vaccine and encephalopathy/encephalitis", and the classified management of literatures about allergic purpura and brachial plexus neuritis. Conclusions: The sustainable updated literature data warehouse of vaccine safety can provide high-quality research data for vaccine safety research, including evidence support for immunization related policy-making and adjustment and vaccine safety-related methodological research or clinical tool development; and further demonstration studies can provide references for building a new methodological framework system for timely and efficient completion of the evidence-based assessment of vaccine safety.

Effect of wheat-grain moxibustion on the expression of 5-HT and cortisol in the serum, and MR and GR in the hippocampus in rats with hypothyroidism complicated with depression / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.@*METHODS@#A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.@*RESULTS@#Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.

Efficacy and Safety of Ultrasound-Guided Radiofrequency Ablation for Primary Hyperparathyroidism: A Prospective Study

Objective@#To assess the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) in patients with primary hyperparathyroidism (PHPT). @*Materials and Methods@#This prospective study enrolled 39 participants (14 male, 25 female; mean age, 59.5 ± 15.3 [range, 18–87] years) between September 1, 2018, and January 31, 2021. All participants had parathyroid lesions causing PHPT, proven biochemically and through imaging. The imaging features of the PHPT nodules, including the shape, margin, size, composition, and location, were evaluated before treatment. Serum intact parathyroid hormone, calcium, and phosphorus levels; parathyroid nodule volume; and PHPT-related symptoms were recorded before and after treatment. We calculated the technical success, biochemical cure, and clinical cure rates for these patients. Complications were evaluated during and after the ablation. @*Results@#Complete ablation was achieved in 38 of the 39 nodules in the 39 enrolled participants. All the patients were treated in one session. The technical success rate was 97.4% (38/39). The mean follow-up duration was 13.2 ± 4.6 (range, 6.0–24.9) months. At 6 and 12 months post-RFA, the biochemical cure rates were 82.1% (32/39) and 84.4% (27/32), respectively, and the clinical cure rates were 100% (39/39) and 96.9% (31/32), respectively. Only 2.6% (1/39) of the patients had recurrent PHPT. At 1, 3, 6, and 12 months after technically successful RFA, 44.7% (17/38), 34.3% (12/35), 15.8% (6/38), and 12.5% (4/32) of participants, respectively, had elevated eucalcemic parathyroid hormone levels. Recurrent laryngeal nerve paralysis occurred in 5.1% (2/39) of the patients, who recovered spontaneously within 1–3 months. @*Conclusion@#US-guided RFA was effective and safe for PHPT patients. RFA may be an alternative treatment tool for patients who cannot tolerate or refuse to undergo surgery.

Research process of reactive oxygen species-based tumor immunomodulation / 药学学报

Reactive oxygen species (ROS) is defined as the electron reduction product of oxygen with high reactivity which can maintain normal physiological functions and redox homeostasis. The tumor microenvironment is in a state of oxidative stress. ROS can affect multiple processes of tumor immune response by modulating the phenotype and functions of tumor cells and immune cells. With the rapid development of immunology, ROS-based tumor immunomodulation has been widely concerned and studied. In this review, the mechanism of ROS participating in tumor immune response is elaborated. Meanwhile, the research process and application of ROS in tumor immunomodulation in recent years are reviewed and analyzed.

Effect of nasolacrimal duct packing combined with sodium hyaluronate gel injection in locating the nasal broken end in lacrimal canaliculus anastomosis which is difficult to find the broken end / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of nasolacrimal duct packing combined with sodium hyaluronate gel injection in locating the nasal broken end in lacrimal canaliculus anastomosis which is difficult to find the broken end.METHODS:A total of 13 patients(13 eyes)with traumatic single lacrimal canaliculus rupture were treated in our hospital. RS lacrimal duct drainage tube was inserted into the lacrimal duct from intact lacrimal canaliculus to fill the nasolacrimal duct, then sodium hyaluronate gel was injected to make sodium hyaluronate gel overflow from the nasal broken end of fractured lacrimal canaliculus, which was used to locate the nasal broken end which was difficult to find and completed the lacrimal anastomosis operation.RESULTS: Among the patients with 13 eyes who were difficult to find the broken end, the nasolacrimal duct was filled with RS lacrimal duct drainage tube. After injection of sodium hyaluronate gel, the gel overflowed from the nasal broken end under direct vision of the microscope, and the lacrimal duct drainage tube was successfully inserted, and the success rate of finding the broken end was 100%. Thirteen eyes were extubated after being placed for 3mo, and then were followed up for 6mo. Among them, 9 eyes were cured, 3 eyes were markedly effective and 1 eye was ineffective. The cure rate was 69%, and the total effective rate was 92%.CONCLUSION: A new technique for rapid location of nasal broken end is proposed for patients in which are difficult to find the broken end. This method is simple to operate and requires a relatively low clinical experience. It is suitable for patients with different degrees of single lacrimal canaliculus rupture and can complete complex lacrimal canaliculus rupture anastomosis in a short time.

Juglone induces proliferation inhibition and apoptosis of cervical cancer cells via promoting c-Myc ubiquitination / 南方医科大学学报

OBJECTIVE@#To observe the expression of c-Myc protein in cervical cancer HeLa cells and explore the effect of juglone on the proliferation and apoptosis of HeLa cells by affecting c-Myc ubiquitination.@*METHODS@#HeLa cells treated with different concentrations (0, 10, 20, or 50 μmol/L) of juglone or with 20 μmol/L juglone for different time lengths were examined for expression of c-Myc protein with Western blotting. The half-life of c-Myc protein was determined using cycloheximide (CHX) and c-Myc protein degradation was detected using coimmunoprecipitation. We also assessed the effects of 20 μmol/L juglone combined with 0, 1.0 or 2.0 μmol/L MG132 (a proteasome inhibitor) on c-Myc expression. The effects of 20 μmol/L juglone on the proliferation and apoptosis of HeLa cells with RNA interference-mediated knockdown of c-Myc were evaluated with MTT assay and flow cytometry.@*RESULTS@#Treatment with juglone significantly lowered c-Myc protein expression in HeLa cells in a concentration-and time-dependent manner (P < 0.05). Juglone obviously shortened the half-life of c-Myc protein, and the addition of MG132 significantly up-regulated the expression level of c-Myc protein (P < 0.05). Juglone treatment also promoted ubiquitination of c-Myc protein in HeLa cells. Compared with the cells transfected with a negative control construct, the cells transfected with si-c-Myc showed significantly decreased proliferation inhibition and a lowered cell rate with early apoptosis after juglone treatment (P < 0.05).@*CONCLUSION@#Juglone inhibits proliferation and promotes apoptosis of HeLa cells by affecting the ubiquitination of c-Myc protein.

Infective endocarditis in pregnancy: A case report / 北京大学学报(医学版)

Infective endocarditis in pregnancy is extremely rare in clinical practice. Guidelines addressing prophylaxis and management of infective endocarditis do not extensively deal with concomitant pregnancy, and case reports on infective endocarditis are scarce. Due to increased blood volume and hemodynamic changes in late pregnancy, endocardial neoplasms are easy to fall off and cause systemic or pulmonary embolism, respiratory, cardiac arrest and sudden death may occur in pregnant women, the fetus can suffer from intrauterine distress and stillbirth at any time, leading to adverse outcomes for pregnant women and fetuses. The disease is dangerous and difficult to treat, which seriously threatens the lives of mothers and babies. Early diagnosis and reasonable treatment can effectively improve the prognosis of patients. The most important method for the treatment of infective endocarditis requires early, adequate, long-term and combined antibiotic therapy. Moreover, surgical controversies regarding indication and timing of treatment exist, especially in pregnancy. In terms of the timing of termination of pregnancy, the timing of cardiac surgery, and the method of surgery, individualized programs must be adopted. A pregnant woman with 30+5 weeks of gestation is reported. She was admitted to hospital due to intermittent chest tightness, suffocation and fever, with grade Ⅲ cardiac insufficiency. Imaging revealed large mitral valve vegetation, 22.0 mm×4.1 mm and 22.0 mm×5.1 mm, respectively, and severe valve regurgitation. Mitral valve perforation was more likely, blood culture suggested Staphylococcus epidermidis infection, after antibiotic conservative treatment, the effect was poor. After the joint consultation including cardiology, neonatology, interventional vascular surgery, anesthesiology, and obstetrics, the combined operation of obstetrics and cardiac surgery was performed in time. The heart was blocked for 60 minutes, the bleeding was 1 200 mL, the newborn was mildly asphyxiated after birth, and the birth weight was 1 890 g. Nine days after the operation, the patient was discharged from the hospital, and the newborn was discharged with the weight of 2 020 g. Critical cases like this require a thorough weighing of risks and benefits followed by swift action to protect the mother and her unborn child. An optimal outcome in a challenging case like this greatly depends on effective interdisciplinary communication, informed consent of the patient, and concerted action among the specialists involved.

A new anisotane-type sesquiterpene from Anisodus tanguticus / 药学学报

To investigate the chemical constituents of Anisodus tanguticus, silica gel column chromatography, Sephadex LH-20 column chromatography, preparative thin layer chromatography, and semi-preparative HPLC were used to separate and purify the chemical constituents from the extract of A. tanguticus. The planar structure of the isolated compound was identified by HRMS, IR, and 2D NMR experiments. The absolute configuration of the isolated compound was determined by a combination of NOESY, coupling constant, circular dichroism (CD), and transition metal chelate reagent dimolybdenum tetraacetate [Mo2(OAc)4]-induced circular dichroism (ICD) data analysis. A new compound of the anisotane-type sesquiterpene (1) was isolated, which was determined to be (1R,2S,3R,4R,6R,7R,9R)-anisotane-11(13)-ene-3,4,9-triol and named anisotanol F. This is the second report of anisotane-type sesquiterpene, which has previously been reported as a novel sesquiterpenoid skeleton by our research group. Furthermore, the cytotoxicity against HUVECs and inhibitory effect on NO release in LPS-induced RAW264.7 cells of compound 1 were investigated. However, the results showed that it was inactive. Compound 1 is a new compound isolated from A. tanguticus. It belongs to the unusual anisotane-type sesquiterpene. This result enriches the chemical composition of A. tanguticus.

Self-rated health status and its influencing factors of medical staff in Lanzhou City / 环境与职业医学

Background Because of high working intensity, high responsibility, and unexpected situations, health care workers may suffer great work pressure, which may lead to health damage. Objective To explore the self-rated health status and its influencing factors such as demographic and occupational-related factors of medical staff in Lanzhou. Methods In-service medical staff were selected by using cluster random sampling method from 18 public hospitals in Lanzhou City and were investigated with a self-made questionnaire and the Self-rated Health Measurement Scale (SRHMS). SRHMS includes 48 items in 10 dimensions, which are divided into three sub-scales of physical health, mental health, and social health, and another independent dimension is overall health. The scores were converted into a percentage scale and expressed as the percentage of measured score to full score; a higher score indicated better health, and >70% was considered good health status. t test, Kruskal-Wallis H test, and Spearman correlation were used to analyze the scores of SRHMS and the demographic and occupational-related factors affecting the scores of physical, mental, and social health sub-scales. Results A total of 2989 valid questionnaires were recovered. There were statistically significant differences in total score and the scores of physical, mental, and social health among medical staff of different age, educational background, length of service, and weekly working hours groups (P < 0.05). The percentage of total score to full score in the medical staff was 71.41%, but the scores of physical, mental, and social health sub-scales and total scale of selected participants were all lower than the corresponding domestic norms (t=−3.323, −12.283, −7.157, −9.659, P < 0.05); the percentage of psychological symptoms and negative emotions in mental health scale to full score was the lowest, only 58.39%. Educational background, length of service, and weekly working hours were negatively correlated with physical health score (r=−0.061, −0.060, −0.165, P < 0.05); professional title was positively correlated with mental health score (r=0.045, P < 0.05), while educational background and weekly working hours were negatively correlated with it (r=−0.051, −0.172, P < 0.05). Monthly income, professional title, and length of service were positively correlated with social health score (r=0.040, 0.049, 0.071, P < 0.05), while educational background and weekly working hours were negatively correlated with it (r=−0.038, −0.110, P < 0.05). Conclusion The self-rated health status of selected medical staff in Lanzhou is generally good, but lower than that of the norm, especially the mental health score is the lowest. The self-rated health score of total scale is correlated with education, length of service, professional title, and working time per week.