Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS / 中国中药杂志

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Application of CRISPR-Cas9 gene editing technology in crop breeding / 生物工程学报

The CRISPR-Cas9 system is composed of a clustered regularly interspaced short palindromic repeat (CRISPR) and its associated proteins, which are widely present in bacteria and archaea, serving as a specific immune protection against viral and phage secondary infections. CRISPR-Cas9 technology is the third generation of targeted genome editing technologies following zinc finger nucleases (ZFNs) and transcription activator like effector nucleases (TALENs). The CRISPR-Cas9 technology is now widely used in various fields. Firstly, this article introduces the generation, working mechanism and advantages of CRISPR-Cas9 technology; secondly, it reviews the applications of CRISPR-Cas9 technology in gene knockout, gene knock-in, gene regulation and genome in breeding and domestication of important food crops such as rice, wheat, maize, soybean and potato. Finally, the article summarizes the current problems and challenges encountered by CRISPR-Cas9 technology and prospects future development and application of CRISPR-Cas9 technology.

A new macrocyclic flavonoid from Onychium japonicum / 药学学报

Seven compounds were isolated from Onychium japonicum by macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were identified by NMR, MS and other spectroscopic methods as onychone A (1), quercetin (2), quercetin-3-O-α-L-rhamnoside (3), kaempferol-7-O-β-D-glucopyranoside (4), kaempferol-3-O-α-L-rhamnopyranoside (5), (-)-prunin (6), and norathyriol (7). Compound 1 is a novel macrocyclic flavonoid, and all the others are reported from this plant for the first time. In vitro cytotoxic activities of compounds 1-7 were evaluated by MTS testing with five cancer cell lines. Compound 7 exhibited weak cytotoxicity against tumor cell lines A549, SMMC-7721, and SW480.

Research progress on pathogenesis and treatment of drug-resistant epilepsy / 药学学报

Epilepsy is a chronic nervous system disease, which affects more than 70 million people all over the world. Although more than 30 kinds of antiepileptic drugs (AEDs) have been on the market, about one third of the patients with epilepsy fail to respond to medical treatment, who become drug-resistant epilepsy patients. Identifying the mechanism and developing effective treatment methods for drug-resistant epilepsy have become a hot area in the field of epilepsy research. This review discussed resent advance on the pathogenesis of drug-resistant epilepsy from the transporter hypothesis, neural network hypothesis and target hypothesis, and we also summarized the existing potential treatment methods and research progress of drug-resistant epilepsy, such as surgical resection, deep brain stimulation, ketogenic diet, precise treatment, and traditional Chinese medicine treatment. Our review may provide useful clues for the mechanisms research and clinical treatments of drug-resistant epilepsy.

Research progress on the mechanism of exosomes in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Exosomes are nanoscale extracellular vesicles that are secreted by a variety of cells in the body. They carry particular miRNA, protein molecules, transcription factors, and other information molecules, and they play a role in the pathophysiological regulation of a number of diseases in the body. Exosomes can persist steadily in biological tissues and bodily fluids. Exosomes have quickly advanced in ophthalmology in recent years due to the extensive studies of exosomes in a variety of fields, such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, corneal disease, glaucoma, and other diseases. The number of people who are blind caused by diabetic retinopathy is rising as living standards rise. However, it is still unclear how diabetic retinopathy works. In recent years, many studies have found that exosomes play an important role in diabetic retinopathy. In this paper, the most recent developments in exosome studies as they relate to the pathogenesis and progression of diabetic retinopathy are reviewed.

Curative effect of full-femtosecond small incision lenticule extraction on the treatment of high myopia based on propensity score matching / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the effect of full-femtosecond small incision lenticule extraction(SMILE)on the treatment of high myopia based on propensity score matching.METHODS: A total of 48 cases(48 eyes)of high myopia patients who underwent SMILE surgery in our hospital from May 2019 to May 2021 were selected as the observation group, and 48 cases(48 eyes)of high myopia patients who underwent FS-LASIK surgery were matched using propensity score matching as the control group. Follow up for 6mo after surgery, the changes in cylindrical, central corneal thickness, uncorrected visual acuity(UCVA), corneal endothelial cell related indicators [percentage of hexagonal endothelial cells(6A), coefficient of variation(CV)of endothelial cell area, central corneal endothelial cell density(ECD)] and corneal biomechanical indicators [simulated Goldman intraocular pressure(IOPg), corneal hysteresis(CH), corneal resistance factor(CRF), corneal compensated intraocular pressure(IOPcc)] between the two groups were compared, and the incidence of complications in both groups of patients was recorded.RESULTS: Both groups of patients showed significant improvements in cylindrical and UCVA at 3 and 6mo after surgery, as well as decreased central corneal thickness, corneal endothelial cells, and corneal biomechanics related indicators. The changes in the observation group were more significant(all P<0.05). During the follow-up period, there was no significant difference in the incidence of complications between the observation group and the control group(8% vs. 17%, P>0.05).CONCLUSION: SMILE has a definite effect on patients with high myopia and is helpful to improve visual acuity.

Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study / 亚洲男科学杂志(英文版)

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development.

Galloway-Mowat Syndrome in an infant caused by OSGEP gene mutation: a case report and literature review / 中国新生儿科杂志

Objective:To summarize the clinical features and pathogenic gene mutation of Galloway-Mowat syndrome (GAMOS).Methods:We retrospectively collected the medical history, physical signs, laboratory findings, imaging, and molecular data of GAMOS in an infant diagnosed at the department of Pediatrics of Women and Children's Hospital, School of Medicine, Xiamen university. Relevant literature up to December 2021, retrieved from PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang and the Chinese Medical Journal Full Text database with the terms of "Galloway-Mowat syndrome", "infant", "WDR73", "LAGE3", "OSGEP", "TP53RK" and "TPRKB".Results:The male infant with dysmorphic facial features and microcephaly at birth gradually displayed growth restriction and developmental delay. He was admitted to hospital at 3 months and 1 day due to "tachypnea for a half day", and suffered from severe pneumonia, urinary tract infection, nephrotic syndrome, repetitive convulsion, septic shock, disseminated intravascular coagulation, acute renal damage and multiple organ failure during hospitalization. He died when his family had given up treatment. Whole exome sequencing revealed a homozygous mutation c.740G>A (p.Arg247Gln) in the OSGEP gene and both of his parents were heterozygous variation carriers. In the total 14 publications (13 were in English and only 1 in Chinese) that were retrieved, with 78 patients from 58 pedigrees. Together with the index case, there were 79 patients in total. The main clinical manifestations were craniofacial and skeletal dysmorphism, as well as nervous system, renal and eye impairment. Obstetric problems were detected in 15 cases (19.0%), including intrauterine growth restriction, microcephaly, oligohydramnios and fetal distress in utero. 49 cases (62.0%) died when reported. The genetic cause of GAMOS had been reported in 79 patients: OSGEP in 36 (45.6%), WDR73 in 29 (36.7%), TP53RK in 7(8.9%), LAGE3 in 5 (6.3%), and TPRKB in 2(2.5%).Conclusions:The main clinical manifestations of GAMOS were craniofacial and skeletal dysmorphism, development delay, leukoencephalopathy, myelination defect, proteinuria and nephrotic syndrome, and associated with poor prognosis. Prenatal findings may be useful for an early diagnosis.

Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.

Cloning and prokaryotic expression analysis of AlCMK from Atractylodes lancea / 药学学报

4-(Cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase (CMK) was one of the key enzymes in the methylerythritol-4-phosphate (MEP) pathway to generate terpenoids. In this study, based on the transcriptome data of Atractylodes lancea, the sequence of the CMK gene was cloned, named AlCMK (GenBank accession number OM283293). The results showed that AlCMK contains a 1 230 bp open reading frame (ORF) encoding 409 amino acids. The deduced protein had a theoretical molecular weight of 44 752.53 and an isoelectric point of 6.67. Transmembrane structure analysis showed that there was no transmembrane structure, and the secondary structure of AlCMK was predicted to be mainly composed of random coil. Homologous alignment revealed that AlCMK shared high sequence identity with the CMK proteins of Tanacetum cinerariifolium, Osmanthus fragrans, Eucommia ulmoides, Lonicera japonica and Salvia miltiorrhiza. Phylogenetic analysis indicated that AlCMK protein had the higher homology with CMK protein of Compositae. The pET-32a-AlCMK prokaryotic expression vector was constructed and a fusion protein with molecular mass of about 65 kDa was expressed in the E. coli BL21 (DE3). The qRT-PCR was used to analyze the expression pattern of AlCMK gene in different tissues and after MeJA treatment. Meanwhile, the enzyme activity was determined by ELISA kit. The results showed that AlCMK gene was tissue-expressed in different origins and its expression was induced by MeJA, and the results of the enzyme activity assay showed that the AlCMK enzyme activity in different regions was higher in the leaves. The subcellular localization showed that AlCMK was located in the chloroplast. This study provides a reference for further elucidating the biological function of AlCMK gene in terpenoid synthesis pathway in Atractylodes lancea.

Design and application of extracorporeal membrane oxygenation transport vehicle / 中华危重病急救医学

With the widespread application of extracorporeal membrane oxygenation (ECMO) technology, ECMO centers have been established in most regions of China, and the demand for ECMO transport is also increasing. Critically ill patients with ECMO carry many catheters. ECMO devices and accessories are cumbersome and numerous, requiring a large amount of manpower to assist in the transfer. At present, most of ECMO transport equipment are vertical carts provided by equipment suppliers, which cannot accommodate all ancillary equipment and are difficult to be loaded into ambulances for transportation. Therefore, critically ill patients face many risks if they need to be transported inter-hospital. A specific vehicle for ECMO patients was designed by the medical staff of the department of critical care medicine of Zhujiang Hospital of Southern Medical University, which integrates the ECMO host, oxygenator, centrifugal pump, portable ventilator, coagulation instrument, injection pump, monitor, oxygen cylinder, and etc., to greatly facilitate the transportionation. This invention obtained the National Utility Model Patent of China (ZL 2019 2 1201261.4). The new ECMO transport vehicle can facilitate the interhospital transport of critically ill patients, reduce the occurrence of accidents, shorten the transport time and reduce the number of transport personnel, and has a good clinical application value.

Epidemiological characteristics of pulmonary tuberculosis patientsaged 60 years and older in Quzhou City / 预防医学

Objective@#To analyze the epidemiological characteristics of pulmonary tuberculosis cases at ages of 60 years and older in Quzhou City, Zhejiang Province, so as to provide the evidence for formulating the pulmonary tuberculosis control strategy among the elderly. @*Methods@#The data pertaining to pulmonary tuberculosis cases at ages of 60 years and older in Quzhou City from 2010 to 2020 were collected through the Tuberculosis Management Information System of the China Disease Prevention and Control Information System. The trends for incidence, population distribution, diagnosis and treatment of pulmonary tuberculosis cases aged 60 years and older were analyzed using a descriptive epidemiological method.@*Results@#Totally 8 754 pulmonary tuberculosis cases aged 60 years and older were reported in Quzhou City from 2010 to 2020, accounting for 47.65% of all pulmonary tuberculosis cases, and the number of pulmonary tuberculosis appeared a tendency towards a rise ( χ2trend=173.320, P<0.001 ), while the incidence of pulmonary tuberculosis showed a tendency towards a decline ( χ2trend=389.820, P<0.001 ), with an annual decline rate of 177.11/105. There were 4 307 smear-positive pulmonary tuberculosis cases, accounting for 58.71% of all smear-positive cases, and the number of smear-positive pulmonary tuberculosis cases showed a tendency towards a rise ( χ2trend=126.320, P<0.001 ), while the proportion of smear-positive cases showed a tendency towards a decline ( χ2trend=21.680, P<0.001 ), with an annual smear-positive rate of 87.14/105. The incidence of pulmonary tuberculosis was 256.94/105 among males and 91.43/105 among females at ages of 60 years and older ( χ2=20.903, P<0.001 ). The highest incidence of pulmonary tuberculosis was seen in patients aged 80 to 84 years ( 235.17/105 ), and farmers were the predominant occupation ( 7 171 cases, 81.92% ), while the highest number of cases was reported in Quzhou City (8 676 cases, 99.11%). There were 7 752 treatment-naïve cases ( 88.55% ), while 5 830 cases with delay in seeking healthcare services, and the proportion of delay in seeking healthcare services showed a tendency towards a rise from 2010 to 2020 ( χ2trend=4.853, P=0.028 ), with an annual mean delay rate of was 66.60%.@*Conclusion@#The incidence of pulmonary tuberculosis appeared a tendency towards a decline among patients aged 60 years and older in Quzhou City from 2010 to 2020, and the elderly aged 80 years and older and farmers should be paid more attention.

Preparation of oxytocin liposomes modified by cell penetrating peptides and evaluation on brain targeting efficiency via intranasal delivery / 药学学报

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Research progress of delivery strategies related mucus barrier in mucosal drug delivery / 药学学报

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity / 神经科学通报·英文版

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.

Effect and Safety of Acupuncture for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of 21 Randomised Controlled Trials / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM).@*METHODS@#PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.@*RESULTS@#Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD -6.46 mg/dL, 95% CI -11.95 to -0.98; moderate-quality evidence) and HOMA-IR (MD -1.23, 95% CI -2.16 to -0.31; low-quality evidence), but comparable changes in HbA1c (MD -0.39%, 95% CI -0.84 to 1.61; very-low-quality evidence), 2hBG (MD -4.99 mg/dL, 95% CI -20.74 to 10.76; low-quality evidence), and FINS (MD -1.32 µIU/mL, 95% CI -3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild.@*CONCLUSIONS@#The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Trial registration No. CRD42018115639).

Research progress of exosomes based targeted delivery of antitumor drugs / 药学学报

Exosomes are one of the most important ways of cell-to-cell communication in living lives. They are involved in major physiological and pathological processes, including drug resistance, infection propagation, cancer development and cardiovascular diseases. The biological functions of exosomes made it possess characteristics of low immunogenicity, high delivery efficiency, ability to cross multiple biological barriers and targeting capacity, which also encourage people to try to use it as a drug carrier to overcome the disadvantages of poor stability, low solubility, low bioavailability and high toxicity of some drugs. In this paper, the latest progress of exosomes in the delivery of antitumor drugs, including small chemotherapeutic drugs, biological macromolecules and nucleic acid drugs, is reviewed. In addition, the isolation, drug loading, and modification method and the application prospect of exosomes are also discussed.

The diagnostic value of changes in peripheral blood cell ratioin children with infectious mononucleosis / 西安交通大学学报(医学版)

【Objective】 To investigate the diagnostic value of neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte (MLR), and lymphocyte (LYM) count in children with infectious mononucleosis (IM). 【Methods】 Clinical and laboratory data of 134 IM children hospitalized between September 2017 and March 2020 were collected. A total of 60 healthy children during the same period were selected as the control group. The subjects’ NLR, MLR, and LYM were calculated according to the results of peripheral blood. The values of NLR, MLR, and LYM in diagnosing and predicting IM were analyzed with ROC. 【Results】 The MLR and LYM values of IM children were significantly higher than those of the control group (P0.05). ROC results showed that the area under the ROC curve (AUC) of NLR was 0.397, AUC of MLR was 0.648, and LYM's AUC was 0.680. The ROC curve AUC of MLR+LYM was 0.878, the optimal threshold was 0.59, the sensitivity was 82.09%, and the specificity was 85.00%. 【Conclusion】 MLR and LYM are independent biomarkers for the prediction of IM in children.

Efficacy Prediction Model for Neoadjuvant Chemotherapy on Breast Cancer Based on Differential Genes Expression / 肿瘤防治研究

Objective To screen out significant differential genes for predicting the effect of neoadjuvant chemotherapy (NAC) and select the most suitable breast cancer patients for NAC. Methods A total of 60 breast cancer patients' samples before and after NAC were collected for high-throughput RNA-Seq. We selected AHNAK, CIDEA, ADIPOQ and AKAP12 as the candidate genes that related to tumor chemotherapeutic resistance. We analyzed the correlation of AHNAK, CIDEA, ADIPOQ, AKAP12 expression levels with the effect of NAC by logistic regression analysis, constructed a prediction model and demonstrated the model by the nomogram. Results AHNAK, CIDEA, ADIPOQ and AKAP12 expression were up-regulated in the residual tumor tissues of non-pCR group after NAC(P < 0.05). Compared with pCR group, non-pCR group presented higher expression levels of AHNAK, CIDEA, ADIPOQ and AKAP12 (P < 0.05). The high expression levels of AHNAK, CIDEA, ADIPOQ and AKAP12 significantly reduced the pCR rate of NAC for breast cancer (P < 0.05). Our prediction model which AHNAK, CIDEA, ADIPOQ and AKAP12 were involved in showed a good fitting effect with H1 test (χ2=6.3967, P=0.4945) and the ROC curve (AUC 0.8249, 95%CI: 0.722-0.9271). Conclusion AHNAK, CIDEA, ADIPOQ and AKAP12 may be novel marker genes for NAC effect on breast cancer. The efficacy prediction model based on this result is expected to be a new method to select the optimal patients of breast cancer for neoadjuvant chemotherapy.

Mechanism of Kaixinsan on Learning and Memory Ability and Synaptic Function of APP/PS1 Mice / 中国实验方剂学杂志

Objective:To explore the underlying protective mechanism of Kaixinsan on learning， memory， and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group， a donepezil （2 mg·kg^-1·d^-1） group， and low- （0.7 g·kg^-1·d^-1）， medium- （1.4 g·kg^-1·d^-1）， and high-dose （2.8 g·kg^-1·d^-1） Kaixinsan groups， and the wild-type mice of the same age in the same litter were assigned to the normal group， with 12 mice in each group. After continuous intragastric administration for two months， the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine （ACh）， choline acetyltransferase （ChAT）， acetylcholinesterase （AChE）， and levels of hippocampal reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Real-time fluorescence-based quantitative polymerase chain reaction （Real- time PCR） was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor （BDNF）， beta-nerve growth factor （NGFB）， discs large homolog (DLG)2， DLG4， and synaptophysin （SYP）. Result:Compared with the normal group， the model group showed prolonged escape latency， reduced number of crossing platforms， shortened stay in the target quadrant （<italic>P</italic><0.01）， decreased number of mitochondria with different shapes and irregular arrangement， some swollen and deformed mitochondria with broken mitochondrial cristae， endolysis， and cytoplasm vacuole， and more cell debris. Additionally， the model group also displayed reduced serum levels of ACh and ChAT， increased AChE （<italic>P</italic><0.01）， elevated hippocampal ROS and MDA （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining SOD and GSH-Px （<italic>P</italic><0.01）， and diminished hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the donepezil group， and the medium- and high-dose Kaixinsan groups showed shortened escape latency， increased number of crossing platforms， prolonged stay in the target quadrant （<italic>P</italic><0.05，<italic>P</italic><0.01）， improved mitochondrial damage with a regular shape （mainly oval shape）， relieved mitochondrial swelling and deformation， and clear mitochondrial cristae. Furthermore， the donepezil group， and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels （<italic>P</italic><0.05，<italic>P</italic><0.01）， blunted AChE activity （<italic>P</italic><0.05）， reduced hippocampal ROS level （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining MDA level （<italic>P</italic><0.05）， potentiated SOD and GSH-Px activities， and up-regulated hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. In the low-dose Kaixinsan group， the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly （<italic>P</italic><0.05）. There was no statistical difference in swimming speed between the groups. Conclusion:Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins， reducing the ultrastructural damage to hippocampal neurons， resisting oxidative stress， and regulating cholinergic neurotransmitters， thereby exerting neuroprotective effects.