Research progress of Posner-Schlossman syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

Posner-Schlossman syndrome(PSS)is a sporadic and recurrent self-limiting anterior uveitis, and its pathogenesis remains unclear. It was considered to be a prostaglandin-mediated inflammatory response. In recent years, it has been found to be related to viral infection, immune genetics, vascular endothelial dysfunction, and other factors. Clinically, the disease is predominantly unilateral. The patients with PSS suffer from increased intraocular pressure, mild pain in the affected eye, as well as blurred vision, and irisopsia. Seldom damage to the optic nerve and visual field was reported. The commonly treatment of PSS is local medication, such as anti-inflammatory drugs and intraocular pressure lowering drugs; otherwise systemic medication can be employed in severe cases. Surgical treatment can be performed for PSS if uncontrolled intraocular pressure elevation, frequent attacks, and optic nerve damage and visual field defect due to prolonged disease course. Early diagnosis and treatment of PSS can effectively reduce glaucoma-related damages. This review discussed the research progress of PSS from various aspects, aiming to provide references for the etiology, pathogenesis, and clinical diagnosis and treatment of this disease.

Research progress of microparticles in traditional Chinese medicine decoction / 药学学报

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice / 中国生物制品学杂志

Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice@#Objective To investigate the effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 crown protein vaccine in mice.Methods The amantadine dimer was synthesized by substitution reaction ligation,hydrolytic acidification reaction ligation and amide condensation reaction ligation,with which as adjuvant,female BALB/c mice were immunized with the receptor-binding domain(RBD).The mice were randomly divided into five groups,six for each as follows:R6A+RBD group[21 μg(0.033 μmol)amantadine dimer+10 μg RBD],Ada+RBD group[10 μg(0.066 μmol)amantadine+10 μg RBD],Alu+RBD group(35 μg aluminum adjuvant+10 μg RBD),RBD group(10 μg RBD)and Blank group(0.9% normal saline),which were immunized i.m.on day 0,14 and 28 respectively.Serum samples were collected from tail vein of mice 7 d after the second dose and 14 d after the last dose and determined for specific IgG antibody levels by ELISA.Results The amantadine dimer was purified by thin layer chromatography(TLC)and identified by electrospray ionization-MS(ESI-MS)positive/negative ion mode.After two times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all higher than those of Ada+RBD group,while lower than those of Alu+RBD group.However,after three times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all significantly higher than those of Ada+RBD and Alu+RBD groups(each F > 30,each P < 0.000 1 and each P < 0.01).Conclusion Amantadine dimer adjuvant enhanced humoral immune response induced by SARS-CoV-2 protein vaccine in mice with good adjuvant effect,which may be used as an alternative adjuvant.This strategy based on existing drug transformation provided a new idea for the development of novel adjuvants.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis / 亚洲男科学杂志(英文版)

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing / 中国中药杂志

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

A family with early onset myopathy caused by MEGF10 gene defect and literature review / 中华儿科杂志

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.

Herbal Textual Research on Rhapontici Radix in Famous Classical Formulas / 中国实验方剂学杂志

This article systematically sorted out and researched the name， origin， harvesting and other aspects of Rhapontici Radix by referring to ancient materia medica， medical books and prescription books， combined with modern literature， in order to provide a reference basis for the development of the famous classical formulas containing this herb. According to the results of the herbal textual research， it can be seen that all the generations of the materia medica have taken Loulu as the proper name， and there are also aliases such as Luligen， Laowenghua and Jiahao. The mainstream base of Rhapontici Radix recorded in the past dynasties was the present Compositae plant Rhaponticum uniflorum， which is mostly used as medicine with roots. Since the Tang dynasty， the stems and leaves of Siphonostegia chinensis have been used as Rhapontici Radix in the northern region. Until modern times， Qizhou Pharmacognosy began to differentiate it into two categories， Qizhou Loulu and Yuzhou Loulu， according to the commodity circulation at that time， producing area and origin， of which Yuzhou Loulu is the roots of Echinops latifolius， a plant of Compositae family. In ancient times， the quality of Loulu was based on "the one that comes out of Shanzhou is the best". However， in modern times， the quality of Qizhou Loulu is better if the surface is black， neat， sturdy， firm， not broken， and without a withered heart， while the quality of Yuzhou Loulu is better if the branches are thick and long with an earthy-brown surface， solid texture and neat in length. In ancient times， most of the harvesting and processing of Loulu was "harvesting the roots in lunar August and drying them in the shade"， while in modern times， the roots are mostly excavated in the spring and autumn， and dried in the sun. Its ancient method of processing is to mix and steam with licorice， nowadays， it is prepared by removing impurities， washing， moistening thoroughly， cutting into thick slices and drying in the sun， and then taking the raw products as medicine. Based on the research conclusion， it is suggested that when developing and utilizing the famous classical formulas containing Loulu， the background of the formula should be verified， and if the original formula indicated the requirement of processing， it should be processed according to the requirement， but if not， it is recommended to use raw products as medicine.

Antioxidant and anti-inflammatory activities of four kinds of Huangshan chrysanthemum / 药学实践杂志

Objective To investigate the antioxidant and anti-inflammatory activities of four kinds of Huangshan chrysanthemum. Methods ABTS, FRAP and DPPH were used to detect the antioxidant activities of Huangshan golden silk chrysanthemum, Huangshan chrysanthemum, Huangshan gongju, and Huangshan dendranthema. Their anti-inflammatory activities were evaluated by NF-κB reporter gene assay and rat foot swelling models. Results The outcomes of ABTS，FRAP and DPPH showed that the water extracts of four kinds of chrysanthemum all had certain antioxidant activities and the activities of Huangshan golden silk chrysanthemum were strongest, followed by Huangshan chrysanthemum , Huangshan gongju , and Huangshan dendranthema. Results of NF-κB reporter gene assay and rat foot swelling models showed that four extracts of chrysanthemum morifolium could inhibit the transcription of NF-κB induced by LPS and alleviate foot swelling of rat induced by carrageenan, with the strongest activity of Huangshan chrysanthemum, followed by Huangshan golden silk chrysanthemum, Huangshan gongju, and Huangshan dendranthema. Conclusion The antioxidant activities of Huangshan golden silk chrysanthemum were strongest, followed by Huangshan chrysanthemum, Huangshan gongju, and Huangshan dendranthema. The anti-inflammatory activities of Huangshan chrysanthemum were strongest, followed by Huangshan golden silk chrysanthemum, Huangshan gongju, and Huangshan dendranthema.

Study on the clinical comprehensive evaluation of blood lipid-regulating drugs in five provinces and regions in Northwest China / 中国药房

OBJECTIVE To explore standardized evaluation process for clinical comprehensive evaluation of blood lipid- regulating drugs and perform rapid assessment of clinical comprehensive evaluation of blood lipid-regulating drugs with different mechanisms so as to provide reference for the drug catalogue selection and rational drug use of medical institutions. METHODS Referring to guidelines and consensus such as the guideline for the management of comprehensive clinical evaluation of drugs， the methods such as literature research， expert interviews， and Delphi expert consultation were used to establish a multi-dimensional and multi-criteria clinical comprehensive evaluation index system and quantitative scoring table for blood lipid-regulating drugs around the two main lines of technical evaluation and policy evaluation. Then 13 blood lipid-regulating drugs with different mechanisms in 21 third-grade class-A medical institutions from five provinces and regions of Northwest China were scored from both technical and policy dimensions to form a comprehensive evaluation result. RESULTS The clinical comprehensive evaluation index system and corresponding rapid evaluation quantitative scoring table were constructed for blood lipid-regulating drugs in the five northwest provinces and regions. The technicalevaluation section included 6 primary indicators， 13 secondary indicators， and 34 tertiary indicators， totaling 110 points. The policy evaluation section included 4 primary indicators and 6 secondary indicators， with a total score of 40 points （30 points for some drugs） and a total score of 150 points （or 140 points）. The scoring results showed that the highest score was atorvastatin， followed by rosuvastatin and simvastatin. CONCLUSIONS Statins are still the cornerstone of drug therapy for patients with dyslipidemia； the rapid evaluation quantitative scoring table constructed in this study is comprehensive， systematic and operable. The evaluation process in this study can provide empirical references for other groups to exploring the standardized path and quality control mechanism of clinical comprehensive evaluation of drugs.

Effects of platelet-rich plasma injection therapy combined with muscle strength training on ankle function in patients with traumatic ankle arthritis / 中国基层医药

Objective:To investigate the effects of platelet-rich plasma injection therapy combined with muscle strength training on ankle function in patients with traumatic ankle arthritis.Methods:The clinical data of 98 patients with traumatic ankle arthritis admitted to The 906 Hospital of PLA Joint Logistics Support Force from January 2020 to January 2021 were retrospectively analyzed. These patients were grouped according to different treatment methods. Patients in the control group ( n = 31) received muscle strength training. Patients in the sodium hyaluronate group ( n = 33) received muscle strength training and intraarticular injection of sodium hyaluronate. Patients in the platelet-rich plasma group ( n = 34) received muscle strength training and intraarticular injection of platelet-rich plasma. Ankle function, excellent and good recovery rate, and muscle strength were compared among the three groups before and after treatment. Results:After treatment, the American Orthopaedic Foot & Ankle Society scores in the control, sodium hyaluronate, and platelet-rich plasma groups were (38.22 ± 3.02) points, (41.55 ± 2.04) points, and (44.22 ± 2.69) points respectively, pain scores were (26.98 ± 4.05) points, (31.22 ± 4.20) points, and (34.44 ± 2.44) points respectively, on-line scores were (6.11 ± 1.41) points, (7.39 ± 1.06) points, and (8.25 ± 1.03) points respectively. There were significant differences in the American Orthopaedic Foot & Ankle Society scores, pain scores, and online scores among the three groups ( F = 43.01, 34.30, 27.21, all P < 0.001). In the control, sodium hyaluronate, and platelet-rich plasma groups, dorsiflexor strength was (103.66 ± 10.69) N·m, (129.33 ± 12.37) N·m, (133.69 ± 10.58) N·m, respectively, plantar flexor strength was (121.36 ± 15.69) N·m, (140.23 ± 14.66) N·m, (144.55±13.55) N·m, respectively, ankle function score was (84.22 ± 2.69) points, (88.55 ± 3.01) points, (92.56 ± 3.55) points, respectively. There were significant differences in dorsiflexor strength, plantar flexor strength, and ankle function score among the three groups ( F = 66.37, 22.70, 58.05, all P < 0.001). There was no difference in adverse reactions among the three groups ( Z = 1.05, P > 0.05). Conclusion:Platelet-rich plasma injection therapy combined with muscle strength training is highly effective on traumatic ankle arthritis and can markedly improve ankle function and prognosis.

Changes of humoral and cellular immune indexes in peripheral blood of children with Kawasaki disease at different stages / 中国医师进修杂志

Objective:To investigate the dynamic change characteristics of peripheral blood interferon-γ (INF-γ), interleukin (IL)-4 levels and T helper cell (Th)1/Th2 balance in acute, subacute and restoration stages of children with Kawasaki disease (KD).Methods:Forty-one children with KD received treatment in Women′s and Children′s Hospital Affiliated of School of Medicine University of Electronic Science and Technology of China, Chengdu Women′s and Children′s Central Hospital from May 2017 to January 2020 were enrolled as the observation group, and 41 healthy children examinee from the same period were enrolled as the control group. Children with KD of the observation group were performed with tuberculin pure protein derivative (PPD) test when acute and restoration stage of KD respectively. Peripheral venous blood were drawn from KD children of the observation group in acute, subacute and restoration stage and the control group respectively, serum immune globulin IgG, IgA, IgM and IgE, serum IFN-γ and IL-4 levels were detected by enzyme linked immunosorbent assay (ELISA).Results:Positive rates of PPD test in the restoration stage was higher than that in the acute stage: 65.85%(27/41) vs.17.07%(7/41), there was statistical difference ( χ2 = 20.10, P<0.05). The levels of serum IgG, IgA, IgM and IgE in the acute stage , subacute stage and restoration stagewere gradually decreased ( P<0.05). The levels of serum IgG, IgA, IgM and IgE in the restoration stage and the control group had no significant differences ( P>0.05). The levels of serum IFN-γ and IFN-γ/IL-4 in the acute stage , subacute stage and restoration stage were gradually increased ( P<0.05), the level of IL-4 was gradually decreased ( P<0.05), but the levels of serum IFN-γ, IL-4 and IFN-γ/IL-4 in the restoration stage and the control group had no significant differences ( P>0.05). Conclusions:Among the children with KD in acute stage, serum level of IFN-γ is decreased while serum IL-4 level is increased, and Th1/Th2 balance shifts to Th2. Along with the stabilization of disease, the levels of serum IFN-γ and IL-4 are normalized, and Th1/Th2 balance presents a recovering trend and they almost recover to normal after entering the restoration stage.

Mechanism of Chemotherapy Resistance of Hepatocellular Carcinoma and Intervention with Chinese Medicine： A Review / 中国实验方剂学杂志

Multidrug resistance （MDR） has been a main culprit behind the failure of chemotherapy in patients with malignant tumors and a major obstacle to improving the life quality and prolonging the survival of patients. Hepatocellular carcinoma cells， the innate drug-resistant cells， are generally insensitive to radiotherapy and chemotherapy. Moreover， as the early symptoms of hepatocellular carcinoma are atypical， most patients are diagnosed at the advanced stage， with short survival period and high recurrence rate. Thus， the sensitivity to chemotherapy drugs is decreased. This explains how MDR becomes one of the important reasons for the failure of primary hepatocellular carcinoma （PHC） treatment. Therefore， it is an urgent task to search for safe and effective chemosensitizers with little adverse effect in the research on the drug resistance of hepatocellular carcinoma. As Chinese medicine has been widely applied in the treatment of tumors， the mechanisms of compound Chinese medicine prescriptions， Chinese medicine injections， and single Chinese medicinal in reversing chemotherapy resistance in liver cancer have attracted the interest of scholars. According to previous reports， the mechanisms can be summarized as increasing intracellular drug concentration， influencing changes in enzyme activity， inducing apoptosis， reversing abnormalities in cellular signaling pathways， and regulating the tumor microenvironment. Traditional Chinese medicine reduces the chemotherapy resistance of hepatocellular carcinoma cells through multiple targets and multiple pathways， thereby improving the chemotherapy sensitivity of the cancer cells and enhancing the toxicity of chemotherapeutic drugs to hepatocellular carcinoma cells. Therefore， exploring the mechanism of MDR of hepatocellular carcinoma from the perspective of traditional Chinese medicine is important for reversing the MDR and is of great reference value for clinical treatment of hepatocellular carcinoma. However， there are few experimental types and adverse effects available. Thus， the multi-mechanism and multi-target experiments and clinical research should be carried out in the future.

Study of intermolecular interactions of piroxicam polymorphs / 药学学报

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

Value of metagenomic next-generation sequencing in children with severe infectious diseases / 中国当代儿科杂志

OBJECTIVES@#To study the application value of metagenomic next-generation sequencing (mNGS) in children with severe infectious diseases.@*METHODS@#An analysis was performed on the clinical data and laboratory test results of 29 children with severe infection who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to December 2020. Conventional pathogen culture was performed for the 29 specimens (27 peripheral blood specimens and 2 pleural effusion specimens) from the 29 children, and mNGS pathogen detection was performed at the same time.@*RESULTS@#Among the 29 children, 2 tested positive by conventional pathogen culture with 2 strains of pathogen, and the detection rate was 7% (2/29); however, 20 children tested positive by mNGS with 38 strains of pathogen, and the detection rate was 69% (20/29). The pathogen detection rate of mNGS was significantly higher than that of conventional pathogen culture (P<0.05), and mNGS could detect the viruses, fungi, and other special pathogens that conventional pathogen culture failed to detect, such as Orientia tsutsugamushi. The univariate analysis showed that gender, routine blood test results, C-reactive protein, procalcitonin, D-dimer, radiological findings, and whether antibiotics were used before admission did not affect the results of mNGS (P>0.05).@*CONCLUSIONS@#Compared with conventional pathogen culture, mNGS is more sensitive for pathogen detection, with fewer interference factors. Therefore, it is a better pathogenic diagnosis method for severe infectious diseases in children.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Preliminary study on differentially expressed proteins in a mouse model of secondary alveolar echinococcosis based on data independent acquisition proteomics / 中国血吸虫病防治杂志

Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. Methods Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. Results A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. Conclusion A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.

Advance in application and efficacy of ketogenic diet therapy in drug-resistant epilepsy caused by gene mutation / 国际儿科学杂志

Genetic factors are important causes of drug-resistant epilepsy.In most cases, epilepsy caused by gene mutation cannot be controlled by existing antiepileptic drugs.Ketogenic diet controls seizures through multi-target mechanism, which is widely used in the treatment of drug-resistant epilepsy caused by gene mutation.In this paper, the advance in application and efficacy of ketogenic diet therapy in 23 kinds of gene mutation related drug-resistant epilepsy is reviewed, which involves energy metabolism, ion channel, mTOR signaling pathway and some other rare diseases.

MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40

Purpose@#Cerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species (ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40) in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion (I/R) injury. @*Materials and Methods@#A mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemia in vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation (OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. The relationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays. @*Results@#Bhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40 overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p was verified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/ R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reverse the effects of miR-494-3p overexpression on ROS production and cell apoptosis. @*Conclusion@#MiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.

Constructions of the scale of difficulty in the extraction of impacted mandibular third molars by using Delphi method / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the relevant indicators affecting difficulty in the extraction of impacted mandibular third molars and score difficulty of different operation and risk indicators, so as to build an intuitive and accurate scale to help operators make more accurate analysis and prediction of difficulty before the operation.@*METHODS@#Based on literature and the clinical review, the difficulty indicators of tooth extraction were summarized. Firstly, 10 doctors from Peking University School and Hospital of Stomatology who had been engaged in alveolar surgery for a long time established an expert nominal group, and then rated whether the summarized indicators needed to be retained in the form of face-to-face questionnaires. A level 1 and 2 item frame for evaluating difficulty in the tooth extraction was formed after discussion; Then Delphi method was used to send a questionnaire to 30 experts by e-mail. After two rounds of scoring and modification, the scale of difficulty in the extraction of impacted mandibular third molars was formed.@*RESULTS@#The recycling rate of two rounds of questionnaires was 100.0%, which showed that the experts were very enthusiastic about the study; The authority coefficients (Cr) of the two rounds of Delphi expert consultation were both 0.92, which showed that the results were representative and authoritative. After two rounds of grading and revision, the variable coefficient (CV) decreased and the Kendall's concordance coefficient (W) increased, which were statistically significant: In the first round, the CV was 0.24 and W was 0.56 (P < 0.001), and in the second, the CV was 0.19 and W was 0.72 (P < 0.001), which indicated that there was a good convergence among the expert opinions. Finally, a scale of difficulty in the tooth extraction containing 12 items at level A and 37 items at level B was formed, including operation difficulty indicators, risk difficulty indicators and common difficulty indicators.@*CONCLUSION@#Based on comprehensive literature retrieval, the study has put forward the concept that difficulty in the extraction of impacted mandibular third molars is composed of operation difficulty and risk difficulty. Using Delphi method, the long-term clinical experience and professional knowledge of experts are transformed into quantitative indicators as a scoring scale. The scale has certain representativeness and authority.

Application of lymphocytes test in peripheral blood of patients with systemic sclerosis during the treatment / 北京大学学报(医学版)

OBJECTIVE@#To explore the significance of lymphocytes in systemic sclerosis (SSc), by detecting the levels of T lymphocytes, B lymphocytes and natural killer (NK) cells, and analyzing the correlation between the lymphocytes and clinical laboratory indexes.@*METHODS@#The numbers and proportion of T, CD4+T, CD8+T, B, and NK cells were detected by flow cytometry in peripheral blood of 32 SSc patients who had taken immunosuppressive drugs and 30 healthy controls (HC). The comparison of the lymphocyte subsets in SSc with them in the HC groups, and the correlation between the lymphocytes and other clinical and laboratory indicators were analyzed by the relevant statistical analysis.@*RESULTS@#Compared with the HC group, the numbers of T, CD4+T, CD8+T, and NK cells in peripheral blood of SSc group, who had taken immunosuppressive drugs, were significantly decreased (P < 0.05). More-over, the proportion of NK cells in peripheral blood of the SSc group was also significantly lower than that in the HC group (P=0.004). In addition, all the lymphocyte subsets were decreased in peripheral blood of more than 65% of the SSc patients who had taken immunosuppressive drugs. Compared with CD4+T normal group, the positivity of Raynaud's phenomenon, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was significantly increased in CD4+T reduction group, respectively (P＝0.024, P < 0.001, P=0.018). ESR was higher in CD8+T reduction group than CD8+T normal group (P＝0.022). The prevalence of fingertip ulcer was significantly increased in B cell decrease group (P=0.019). Compared with NK cell normal group, the prevalence of fingertip ulcer was significantly increased in NK cell lower group (P=0.033), IgM was remarkablely decreased yet (P=0.049). The correlation analysis showed that ESR was negatively correlated with the counts of T lymphocytes (r＝－0.455, P＝0.009), CD4+T lymphocytes (r＝－0.416, P＝0.018), CD8+T lymphocytes (r＝－0.430, P=0.014), B cells (r＝－0.366, P＝0.039).@*CONCLUSION@#The number of CD4+T, CD8+T, B, and NK cells significantly decreased in peripheral blood of SSc patients who had used immunosuppressive drugs, some lymphocyte subsets might be related with Raynaud's phenomenon and fingertip ulcer, and reflected the disease activity by negatively correlated with ESR and CRP; the numbers of lymphocyte subsets in peripheral blood should be detected regularly in SSc patients who had taken immunosuppressive drugs.