Analysis on Components Absorbed into Blood and Cerebrospinal Fluid of Schisandrae Chinensis Fructus Based on Sequential Metabolism / 中国实验方剂学杂志

ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus（SCF） based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism， intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration， and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC Q-Exactive Orbitrap MS） was used to analyze and compare the differences in the spectra of SCF extract， blank plasma， administered plasma， blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column（2.1 mm×100 mm， 1.7 µm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-7 min， 95%B； 7-12 min， 95%-35%B； 12-17 min， 35%-15%B； 17-20 min， 15%-12%B； 20-22 min， 12%-5%B； 22-23 min， 5%B； 23-25 min， 5%-95%B； 25-28 min， 95%B）. And heated electrospray ionization（HESI） was used with positive and negative ion modes， the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time， characteristic fragments， molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF， including lignans， flavonoids， amino acids， tannins， and others， of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation， methylation， demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats， it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.

Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases.

AF6, a known polarity protein, contributes to the maintenance of homeostasis while ensuring tissue architecture, repair, and integrity. Mice that lack AF6 display embryonic lethality owing to cell-cell junction disruption. However, we show AF6 promotes necroptosis via regulating the ubiquitination of RIPK1 by directly interact with the intermediate domain of RIPK1, which was mediated by the deubiquitylase enzyme USP21. Consistently, while injection of mice with an adenovirus providing AF6 overexpression resulted in accelerated TNFα-induced necroptosis-mediated mortality in vivo, we observed that mice with hepatocyte-specific deletion of AF6 prevented hepatocytes from necroptosis and the subsequent inflammatory response in various liver diseases model, including non-alcoholic steatohepatitis (NASH) and the systemic inflammatory response syndrome (SIRS).Together, these data suggest that AF6 represents a novel regulator of RIPK1-RIPK3 dependent necroptotic pathway. Thus, the AF6-RIPK1-USP21 axis are potential therapeutic targets for treatment of various liver injuries and metabolic diseases.

Research progress of Mycobacterium abscessus complex diseases / 中华临床感染病杂志

Mycobacterium abscessus complex (MABC), a rapidly growing nontuberculous mycobacterium, has received increasing attention worldwide due to its rising isolation rate. The similarity of symptoms between MABC pulmonary disease and tuberculosis, different treatment methods required by different subtypes, as well as high levels of innate, adaptive and acquired antibiotic resistance, make MABC treatment more difficult and lead to unfavorable clinical outcomes of patients. This article reviews the basic characteristics, common antibiotic resistance mechanisms, as well as diagnosis and treatment of MABC, to provide reference for future research and clinical treatment of MABC lung disease.

Correlation analysis of BRAF V600E mutation with clinical pathological features and prognosis of differentiated thyroid cancer patients with different risk stratification / 中华核医学与分子影像杂志

Objective:To explore the relationship between B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation and clinical pathological features in patients with differentiated thyroid cancer (DTC), and to evaluate the value of BRAF V600E mutation in predicting the efficacy and follow-up of 131I treatment in DTC patients with different risk stratification. Methods:From January 2018 to June 2022, 893 DTC patients (205 males, 688 females, age (42.3±11.9) years) treated with 131I after total thyroidectomy in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Patients were divided into BRAF V600E mutation group ( n=729) and wild-type group ( n=164). According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into low-risk (39 cases), medium-risk (498 cases) and high-risk (356 cases), and the curative effect was divided into excellent response (ER) and non-excellent response (NER). The χ2 test, independent-sample t test and Mann-Whitney U test were used to compare differences between the two groups. Logistic regression analysis was performed to predict the influencing factors of treatment effect in DTC patients with different risk stratification. Results:The differences in age≥45 years, N stage, unilateral or bilateral DTC, multifocus, mode of operation, number and size of metastatic lymph nodes were statistically significant between BRAF V600E mutation group and wild-type group ( χ2 values: 4.45-17.40, t=-4.08, z=-3.08, all P<0.05). In medium- and high-risk stratification, the stimulated thyroglobulin (sTg) levels before and after 131I treatment were slightly higher in the BRAF V600E mutation group, while significantly sharp decreased of sTg and thyroglobulin antibody (TgAb) in wild-type group ( z value: from -9.30 to -2.65, all P<0.05). In medium- and high-risk stratification, 69.0%(60/87) and 64.3%(45/70) of BRAF V600E wild-type patients reached ER after 131I treatment, which were higher than those of mutant patients (57.4%(236/411) and 45.8%(131/286); χ2 values: 3.96, 7.39, P values: 0.046, 0.007). BRAF V600E mutation was the independent predictor affecting the efficacy of 131I treatment in DTC patients with medium- and high-risk stratification (odds ratio ( OR): 0.411 (95% CI: 0.196-0.864), 0.192 (95% CI: 0.096-0.384), P values: 0.019, <0.001). Conclusions:DTC patients with BRAF V600E mutation are related to the high invasiveness, and show poor improvement in biochemical indicators after initial 131I treatment. In addition, BRAF V600E mutation is an important factor in predicting the therapeutic effect of 131I in DTC patients with medium- and high-risk stratification.

Predictive value of metabolic tumor volume and total lesion glycolysis in 18F-FDG PET/CT imaging for prognosis in patients with extensive-stage small cell lung cancer / 中华核医学与分子影像杂志

Objective:To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with extensive-stage small cell lung cancer (ES-SCLC).Methods:From March 2019 to June 2020, 69 patients (55 males, 14 females, age: 38-87 years) with ES-SCLC who underwent pretreatment 18F-FDG PET/CT in First Affiliated Hospital of Zhengzhou University were retrospectively enrolled. The variables including gender, age, smoking, weight loss, liver metastasis, bone metastasis, malignant effusion, SUV max of the primary tumor, whole-body MTV (wbMTV) and whole-body TLG (wbTLG) (including wbMTV 40%, wbTLG 40%, wbMTV 2.5 and wbTLG 2.5) were analyzed. The predictors of overall survival (OS) were analyzed by using Kaplan-Meier method (log-rank test). Results:Of 69 ES-SCLC patients, 43(62%) died and 26(38%) were still alive by the end of follow-up, with a median survival time of 15.0(95% CI: 11.7-18.3) months. Univariate analysis revealed that age ( χ2=4.53, P=0.033), bone metastasis ( χ2=18.05, P<0.001), liver metastasis ( χ2=27.94, P<0.001), wbMTV 2.5 ( χ2=3.98, P=0.046), and wbTLG 2.5( χ2=5.80, P=0.016) were significant predictors of OS. Conclusion:wbMTV 2.5 and wbTLG 2.5 are assosciated with OS and may provide some reference value for predicting the prognosis of ES-SCLC patients.

Effect of normal iodized salt diet on urinary iodine concentration and iodine uptake rate in patients with differentiated thyroid cancer before 131I treatment / 中华核医学与分子影像杂志

Objective:To investigate the effects of normal iodized salt diet on urinary iodine concentration and iodine uptake rate in patients with differentiated thyroid cancer (DTC) before 131I treatment. Methods:A prospective study was conducted on patients with DTC (59 male patients and 130 female patients, age (43.7±12.2) years) who received 131I treatment for the first time after total thyroidectomy in the First Affiliated Hospital of Zhengzhou University between January 2021 and April 2022. Patients were divided into normal iodized salt diet group and limited iodized salt diet group according to whether iodized salt diet was administered 4 weeks before 131I treatment. The age, gender, urinary iodine concentration, iodine uptake rate and tumor risk stratification of the two groups were compared by independent-sample t test or χ2 test. In addition, according to the concentration of urinary iodine, patients were divided into group a1 (urinary iodine <200 μg/L) and group a2 (urinary iodine ≥200 μg/L). Logistic regression analysis was used to analyze the factors affecting urinary iodine concentration. Results:The urinary iodine concentration of normal iodized salt diet group was not significantly different from that of non-iodized salt diet group ((140.53±76.66) vs (121.74±74.64) μg/L; t=1.67, P=0.489). The iodine uptake rates at 2 h, 4 h and 24 h in the 2 groups were (3.77±1.06)% vs (3.42±0.97)%, (3.33±1.07)% vs (3.21±1.15)%, (2.90±2.60)% vs (3.23±2.94)%, respectively ( t values: 2.33, 0.68, -0.81, all P>0.05). There were no significant differences in age ( t=0.56, P=0.889), gender ( χ2=1.33, P=0.250) and tumor risk stratification ( χ2=0.14, P=0.709) between the two groups. Logistic regression analysis showed that tumor risk stratification was associated with urinary iodine concentration (odds ratio ( OR)=3.914, 95% CI: 1.505-10.176; P=0.005). Conclusion:Normal iodized salt diet may have no effect on urinary iodine concentration and iodine uptake rate of patients with DTC before 131I treatment.

Preparation of 89Zr-labeled mesenchymal stem cells and PET monitoring in mice with systemic lupus erythematosus / 中华核医学与分子影像杂志

Objective:To label mesenchymal stem cells (MSCs) with 89Zr-oxine complex, and assess its characteristics of PET imaging in systemic lupus erythematosus (SLE) model (MRL/lpr mice). Methods:SLE mice were screened by 18F-FDG PET imaging. 89Zr-oxine was prepared and used for labeling MSCs (10 6 MSCs and 1 MBq 89Zr-oxine). 89Zr-oxine-labeled MSCs (0.2 MBq) were injected into MRL/lpr mice and BALB/c mice (each n=5) via tail vein at a dose of 1.2×10 6 cells per mouse, and followed with microPET imaging in vivo at 2 h, 6 h, 1 d, 3 d, 7 d, 10 d and 14 d after injection. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used to analyze the data. Results:MSCs was successfully labeled with 89Zr-oxine, with the labeling efficiency of 20% and cell viability >90%. MicroPET imaging showed that MSCs were mainly distributed in lungs and the liver sites at 2 h after injection. The number of MSCs homing to kidneys of MRL/lpr mice ( n=5) increased significantly 24 h after the injection, and the renal uptake of MSCs in MRL/lpr mice was much higher than that in BALB/c mice ((8.28±1.27) vs (4.33±0.94) %ID/g; t=3.54, P=0.024). The renal uptake increased firstly and then decreased and then leveled off, indicating MSCs homing to kidneys. Conclusions:A method for 89Zr-oxine labeling of MSCs is successfully established. 89Zr-labeled MSCs can home to kidneys of SLE mice. PET imaging of 89Zr-labeled MSCs can be effectively used to explore the in vivo distribution and migration behavior of transplanted MSCs during the treatment of diseases such as SLE.

Intervention of Traditional Chinese and Western Medicine in NLRP3 Inflammasome-mediated Digestive System Diseases： A Review / 中国实验方剂学杂志

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 （NLRP3） inflammasome as an essential component of the innate system is implicated in the pathogenesis of several human inflammatory diseases. Studies have confirmed its association with digestive system diseases such as ulcerative colitis， Crohn's disease， and acute pancreatitis， suggesting that the NLRP3 inflammasome plays a role in the initiation and progression of these diseases. Based on the mechanism of NLRP3 inflammasome activation and the pathways that mediate the inflammatory response， this article introduced the relationship between the NLRP3 inflammasome and the pathogenesis of multiple digestive system diseases and the Chinese and western medical therapies. Traditional Chinese medicine （TCM） has demonstrated definite effects on the NLRP3 inflammasome-mediated digestive system diseases. Some single Chinese medicines or TCM prescriptions can treat digestive system diseases by activating or inhibiting NLRP3 inflammasome activation. NLRP3 inflammasome can receive a variety of endogenous and exogenous stimulatory signals， which can initiate， activate， and mediate inflammatory responses. The inflammasome formation and downstream inflammatory cytokines are involved in not only the inflammatory responses but also the development and progression of multiple digestive system diseases. Therefore， the NLRP3 inflammasome can serve as an ideal target for disease treatment. The future rediscovery and in-depth studies of multiple inflammasomes will shed new light on the treatment of multiple digestive system diseases.

Study on the medication law and mechanism of treatment of lumbar disc herniation by national Traditional Chinese Medicine master Liu Bailing based on data mining and network pharmacology / 国际中医中药杂志

Objective:To explore the core prescriptions and mechanism of national TCM master Liu Bailing in the treatment of lumbar disc herniation (LDH) based on data mining and network pharmacology methods; To provide the clinical reference for the treatment of LDH.Methods:The cases of LDH treated by Professor Liu in Affiliated Hospital of Changchun University of Chinese Medicine, from January 1, 2011 to December 31, 2019 were collected and analyzed. Hierarchical clustering and association rules were used to analyze the medication rules and core prescriptions. TCMSP, GeneCards, ETCM, SymMap, DAVID, etc. were used to analyze the network pharmacology of the core compounds in treating LDH and symptoms, and reveal the mechanism.Results:A total of 1 334 prescriptions were included, involving 201 kinds of Chinese materia medica, among which the medicinal property was mainly warm, the flavor was mainly sweet and the meridians were mainly liver meridian and kidney meridian; the core medicines for the treatment of LDH included Aconiti Lateralis Radix Praeparata, Spatholobi Caulis, Cinnamomi Cortex, Corydalis Rhizoma, Eucommiae Cortex, Paederia Foetida and Amomi Fructus, reflecting that Professor Liu Bailing often treats LDH from the perspective of kidney deficiency, and commonly uses the treatment methods of dispelling wind, relieving pain, warming yang and benefiting the kidney. The core prescriptions mainly participated in three pathways of cancer, immunity and cell metabolism, including PI3K-Akt signaling pathway, TNF signaling pathway and FoxO signaling pathway. Conclusion:Professor Liu Bailing's treatment of LDH focuses on overall dialectical treatment, which mainly dispels wind, relieves pain, warms yang and benefits the kidney and the mechanism of the core prescriptions may lie in diminishing the inflammatory response. The core prescriptions may treat LDH by regulating the immune response and cellular physiological functions.

Investigation of occupational hazard emergencies in power grid enterprises in three regions from 2018 to 2020 / 中国职业医学

Objective: To analyze the occurrence and risk factors of various occupational hazard incidents in China's power grid enterprises. Methods: A total of 4 191 workers from eight power grid enterprises in Jilin Province, Shandong Province, and Chongqing City were selected using a convenience sampling method. Their exposure in workplace and the occurrence of various occupational hazard incidents from 2018 to 2020 were investigated. Results: Among the participants, 71.7% were engaged in outdoor operations. The incidence rates of occupational hazard emergency, ranking from high to low, were electric ophthalmia, acute mountain sickness, heatstroke, electro-flash dermatitis, sunburn, cold injury, solar ophthalmia, and gas poisoning in confined space, with the rate of 42.3%, 42.3%, 38.1%, 24.3%, 17.4%, 16.5%, 10.0%, and 1.3%, respectively (P<0.01). The results of multivariate logistic regression analysis showed that workers in Jilin Province had a higher risk of cold injury compared to those in Shandong Province and Chongqing City (all P<0.01). Workers in Chongqing City had a higher risk of solar ophthalmia than those in Jilin Province (P<0.01). Workers in inspection and maintenance positions had a higher risk of heatstroke and sunburn compared to those in substation positions (all P<0.05). Power grid workers with protective systems in enterprises had a lower risk of sunburn and solar ophthalmia compared to those without protective systems (all P<0.01). The risks of sunburn and solar ophthalmia among power grid workers increased with age and daily outdoor working time (all P<0.05). Taking protective measures was a protective factor against heatstroke and cold injury (all P<0.01). Conclusion: Power grid workers face the risk of various occupational hazard incidents. Relevant organizations should conduct targeted preventive measures based on regional and worker characteristics, and ensure the implementation of protective systems in different work environments.

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial / 医学前沿

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

Advances in anti-invasive fungal drug delivery systems / 浙江大学学报·医学版

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.

Establishment of Reference Values for Early Auditory Preverbal Skills of Children with Cochlear Implants.

Auditory and verbal abilities of children with early cochlear implant (CI) surgery usually take some time to develop, and a reference index of early development for horizontal comparisons is urgently needed to guide the mapping process and adjust rehabilitation programs. Therefore, the aim of this study was to establish a reference value for early auditory preverbal skills development in children with CI and investigate the developmental curve and influencing factors for these children. The LittlEARS® Auditory Questionnaire (LEAQ) scores of 287 eligible Chinese participants were obtained at 1, 2, 3, 6, 9, 12, 18, 24, 28, and 36 months interval after CI activation. The median and standard deviation of the LEAQ score of each hearing stage for these children with different activation ages were calculated to establish the reference values. Quadratic regression was conducted to fit the expected developmental curve of the LEAQ score (y=-0.057x2+2.55x+5.45 [0 to 20 months]). With a linear mixed-effects model, we found that the receptive auditory behavior increased rapidly after CI activation, while expressive language skills developed at a steady rate. We also found that the following factors all significantly influenced the LEAQ: the duration of CI use, the development quotient, age of implantation and activation, and the presence of large vestibular aqueduct syndrome or auditory neuropathy spectrum disorder. The reference values and the expected developmental curve for the LEAQ in children with CI established by the present study provides guidance to clinicians and parents as well as realistic expectations regarding language and speech outcomes.

Comparison of foramen magnum decompression with and without duraplasty in the treatment of adult Chiari malformation Type I: a meta-analysis and systematic review.

AIM: Some meta-analyses have focused on foramen magnum decompression with duraplasty (PFDD) and without duraplasty (PFD) in paediatric or mixed populations. Nevertheless, no meta-analysis has evaluated adults only. This study aimed to include new relevant findings in a systematic review to provide the first comparison of PFDD and PFD in adult CM-I. MATERIAL AND METHODS: We retrospectively searched Web of Science, PubMed, Embase and ClinicalTrials.gov to summarize all relevant published papers on adults. A systemic review was adopted to evaluate clinical or radiological improvement, surgical complications, and reoperation rates between the PFD and PFDD groups. RESULTS: Nine papers containing information on 497 adult participants met the criteria. PFDD was related to a lower revision rate (RR=2.96, 95% CI: 1.34-6.51, P=0.007) but a higher complication rate (RR=0.35, 95% CI: 0.22-0.55, P 0.00001). No significant difference was noted between PFD and PFDD in terms of overall symptom improvement (RR=0.93, 95% CI: 0.84-1.03, P = 0.17) or syringomyelia reduction (RR=0.84, 95% CI: 0.63-1.12, P = 0.24). No significant difference in symptom improvement was observed between patients with syringomyelia (RR=0.86, 95% CI: 0.69-1.08, P = 0.20) and patients without syringomyelia (RR=0.94, 95% CI: 0.68-1.30, P = 0.73). CONCLUSION: This systematic review of observational studies reveals that PFDD may provide lower revision rates but pose a higher risk than PFD in the management of CM-I in adults. However, PFD is similar to PFDD in clinical and radiological improvements.

Amentoflavone attenuates Listeria monocytogenes pathogenicity through an LLO-dependent mechanism.

BACKGROUND AND PURPOSE: L. monocytogenes remain a leading cause of foodborne infection. Listeriolysin O (LLO), an indispensable virulence determinant involved in diverse pathogenic mechanisms of L. monocytogenes infection, represents a promising therapeutic target. In this study, we sought to identify an effective inhibitor of LLO pore formation and its mechanism of action in the treatment of L. monocytogenes infection. EXPERIMENTAL APPROACH: Haemolysis assays were carried out to screen an effective LLO inhibitor. The interaction between candidate and LLO was investigated using surface plasmon resonance and molecular docking. The effect of candidate on LLO-mediated cytotoxicity, barrier disruption and immune response were investigated. Finally, the in vivo effect of candidate on mice challenged with L. monocytogenes was examined. KEY RESULTS: Amentoflavone, a natural flavone present in traditional Chinese herbs, effectively inhibited LLO pore formation by engaging the residues Lys93, Asp416, Tyr469 and Lys505 in LLO. Amentoflavone dose-dependently reduced L. monocytogenes-induced cell injury in an LLO-dependent manner. In the Caco-2 monolayer model, amentoflavone maintained the integrity of the epithelial barrier exposed to LLO. Amentoflavone inhibited the inflammatory response evoked by L. monocytogenes in an LLO-dependent manner, and inhibition was attributed to ability to block perforation-associated K+ efflux and Ca2+ influx. In the mouse infection model, amentoflavone treatment significantly reduced bacterial burden and pathological lesions in target organs, with a significant increase in survival rate. CONCLUSIONS AND IMPLICATIONS: Amentoflavone reduced the pathogenicity of L. monocytogenes by specifically inhibiting LLO pore formation, and this may represent a potential treatment for L. monocytogenes infection.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Trends of hospitalized cases of children′s hospitals in China before and after COVID-19 / 中华医院管理杂志

Objective:To analyze the impact of COVID-19 on the number of hospitalization and the disease spectrum of children′s hospitals in China, so as to provide scientific basis for improving the epidemic response policy of children′s hospitals and restoring hospital operations.Methods:Discharged patients from 27 children′s hospitals from January 1, 2019, to December 31, 2020, were selected from the FUTang Updating medical Records(FUTURE) Database. The ratio of discharge number in 2020 to that in 2019 was calculated. Age groups, disease types, and discharge months were further divided to calculate the ratio of discharge numbers under different conditions.Results:The total number of discharged patients in 2020 was 76.76% of the total number in 2019. In terms of discharge time, the ratio rose slowly from the lowest values in February and March, and reached about 90% of the same period of 2019 at the end of 2020. In terms of age, the biggest change in the discharge number was among children aged 1-3 years, which was 71.87% in 2019. In terms of disease classifications, respiratory diseases changed the most in the number of discharged patients in 2020, accounting for 56.03% of that in 2019. The top five hospitalized diseases of children did not change, while the other ranks changed slightly.Conclusions:COVID-19 has a huge and lasting impact on the number of hospitalizations in children′s hospitals, and the hospitals should develop multiple approaches such as online medical care to cope with the long-term negative impact of the pandemic.

Effect of plastic and aesthetic surgery on complex facial injuries in children / 中华医学美学美容杂志

Objective:To analyze the anatomical distribution of complex facial injuries (woun-ds ≥8 cm in length and involving two or more anatomical areas) in children, and to explore the effect of plastic and aesthetic surgery.Methods:A total of 157 children with complex facial injury were admitted to the Plastic Surgery Department of Hangzhou Plastic Surgery Hospital from January 2019 to June 2021, including 94 males and 63 females, aged from 2 to 18 years, with an average age of 6.2 years. The wound length was 8-20 cm, with an average length of 10.3 cm. Plastic surgery techniques were used to design different primary repair schemes according to specific wound conditions, and early postoperative scar prevention and treatment were carried out.Results:In 157 cases, 331 anatomical areas were involved, most of which were buccal (75 sites). The injury caused by sharp instruments (glass, ceramic tile, cutting tools, etc.) ranked the first place with 78 cases. All patients were followed up for more than 3 months, and the results showed 146 cases of primary healing, 11 cases of delayed healing, 8 cases of scar hyperplasia, 149 cases of good morphological and functional recovery.Conclusions:The advantages of using plastic and cosmetic surgery techniques to treat complex facial injuries lie in the emphasis on anatomical and functional reduction and tension-reducing suture, combined with a variety of postoperative scar prevention and treatment measures, and the results are satisfactory.

Evaluation value of drug balloon therapy for intracranial atherosclerotic stenosis based on high-resolution vascular wall MRI / 中华放射学杂志

Objective:To explore the value of high resolution vascular wall MRI (VW-MRI) in drug balloon therapy of intracranial atherosclerotic stenosis.Methods:A total of 21 patients with intracranial atherosclerotic stenosis admitted to the First Affiliated Hospital of Shandong First Medical University from September 2019 to July 2021 were retrospectively analyzed, aged 22-73 (49±15) years, including 15 males and 6 females. All patients were treated with SeQuent Please drug coated balloon recanalization, and performed digital subtraction angiography (DSA), routine MRI and VW-MRI examinations within one week before operation and 2 to 3 months after treatment. The changes of atherosclerotic plaque area, length, enhancement index and stenosis degree before and after recanalization were evaluated. Paired t-test or Wilcoxon test was separately used to compare the difference before and after operation. The value of plaque characteristics in evaluating postoperative efficacy was analyzed by the receiver operating characteristic (ROC) curve. Pearson correlation analysis and Bland-Altman images method were used to test the correlation and consistency of VW-MRI and DSA in measuring the lumen stenosis degree. Results:After endovascular treatment with drug-coated balloon, the plaque area [(1.86±1.28)mm 2], length [3(2, 4)mm],enhancement index [(60±20)%] and lumen stenosis degree [(28±16)%] were significantly lower than those before endovascular treatment [(5.97±1.15)mm 2, t=10.93, P<0.001; 7(6, 9)mm, Z=-3.94, P<0.001; (107±46)%, t=4.26, P<0.001; (89±5)%, t=17.27, P<0.001]. The plaque area, length and enhancement index showed diagnostic value for evaluating the endovascular treatment efficacy (area under the ROC curve=0.89, 0.86, 0.74, respectively). Stenosis degree measured by VW-MRI had a positive correlation ( rpreoperative=0.66, P<0.001; rpostoperative=0.96, P<0.001) and consistency with DSA before and after recanalization. Conclusion:VW-MRI can be used to comprehensively and effectively evaluate treatment effect after endovascular treatment from the changes of plaque basic characteristics and stenosis degree, which is a good imaging follow-up tool.