Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Effects of intensive pharmaceutical intervention led by clinical pharmacists on the risk of ischemic stroke in hypertensive patients / 中国药房

OBJECTIVE To explore the effects of intensive pharmaceutical intervention led by clinical pharmacists on hypertension patients with medium and high risk of ischemic stroke. METHODS The hypertension outpatients with medium and high risk of ischemic stroke， who were assessed by the modified Framingham stroke scale in Zhengzhou People’s Hospital from Oct. 2019 to Apr. 2020， were randomly divided into control group and intervention group， with 200 cases in each group. Patients in the control group received conventional treatment without pharmaceutical intervention； on the basis of conventional treatment， patients in the intervention group received 12-month intensive pharmaceutical intervention （grading management of compliance+ regular follow-up， involving medication education and guidance， blood glucose， blood pressure， blood lipid management and healthy life guidance） provided by clinical pharmacists. The blood glucose indexes， blood lipid indexes， blood pressure compliance rate， medication compliance， 10-year stroke risk and stroke incidence were compared between two groups at baseline and 12 months after enrollment. RESULTS After 12 months of enrollment， the level of low-density lipoprotein cholesterol （LDL-C） in intervention group was significantly lower than that in the same group at baseline， and the levels of fasting blood glucose， glycosylated hemoglobin， total cholesterol and LDL-C in intervention group were significantly lower than those in control group at the same time points （P＜0.05 or P＜0.01）. The compliance rate of blood pressure and medication compliance in intervention group were significantly higher or better than those in control group （P＜0.01）. There were 12 and 15 patients in control group and intervention group turned into low-risk ones respectively， and the proportion of high-risk patients in intervention group was significantly lower than that in control group（P＜0.01）， while the proportion of medium-risk patients was significantly higher than that in control group（P＜0.05）； the incidence of stroke in intervention group was significantly lower than that in control group （1.0% vs. 4.5%， P＜0.05）. CONCLUSIONS The pharmaceutical intensive intervention led by clinical pharmacists can reduce blood glucose and blood lipid levels of hypertensive outpatients， improve their blood pressure compliance rate and medication compliance， and help reduce the risk of stroke.

Clinical study of using basement membrane biological products in pelvic floor reconstruction during pelvic exenteration / 中华胃肠外科杂志

Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study / 中华病理学杂志

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

Research progress in optimization of therapeutic effect of antibodies against flavivirus / 中华微生物学和免疫学杂志

Flaviviruses are a class of positive-strand RNA viruses mainly transmitted by arthropods, which can cause high mortality and morbidity worldwide. At present, there is no specific therapy. Therapeutic antibodies bring hope for the treatment of flavivirus infection, but the antibody-dependent enhancement (ADE) effect induced by flavivirus infection can lead to disease progression. The ideal therapeutic antibodies against flaviviruses should not only treat flavivirus infection, but also avoid the harm caused by ADE. Therefore, researchers have optimized some of the antibodies to seek the best therapeutic antibodies. This review briefly described the research progress and mechanism of therapeutic antibodies against flaviviruses as well as some strategies to reduce the ADE effect induced by the therapeutic antibodies.

Establishment of an in vivo neutralization model based on H5N1 pseudovirus / 中华微生物学和免疫学杂志

Objective:To establish an in vivo infection model of H5N1 pseudovirus and to detect the neutralizing activity of FHA3 antibody using this model. Methods:Based on the sequence information of hemagglutinin (HA) and neuraminidase (NA) of A/Anhui/1/2005/H5N1 strain, two recombinant plasmids of pcDNA3.1-HA5 and pcDNA3.1-NA1 were constructed. The two plasmids and plasmid pNL4-3.Luc.R-E- were co-transfected into 293T cells to prepare H5N1 pseudovirus supernatant. The morphology of pseudovirus particles in the supernatant was observed by electron microscopy. MDCK cells were infected with the pseudovirus supernatant and the virus titer was detected. BALB/c mice were injected with the pseudovirus supernatant by intraperitoneal injection and subjected to bioluminescence imaging at 2, 5, 8, and 12 d after infection to detect the pseudovirus infection in vivo. The functional activity of FHA3 antibody in vivo was evaluated using the established mouse infection model. Results:The recombinant plasmids pcDNA3.1-HA5 and pcDNA3.1-NA1 were correctly constructed and could be used to prepare pseudovirus supernatants of high titer by co-transfecting 293T cells with the plasmid pNL4-3.Luc.R-E-. The virus particles were round under electron microscope. H5N1 pseudovirus-infected mice exhibits strong fluorescence signals, which were attenuated by FHA3 treatment before challenge.Conclusions:The in vivo infection model of H5N1 pseudovirus was successfully constructed and FHA3 antibody was proved to be protective against the pseudovirus infection.

Fabry disease: recent advances in precision treatment / 中华肾脏病杂志

Fabry disease is a X-linked inherited lysosomal storage disease. The pathogenesis is that mutations in the GLA gene lead to the decrease or lack of α-galactosidase A activity, followed by the accumulation of substrate and its intermediate metabolites in cells and tissues, eventually leading to multiple organ injury. The rise of specific treatment and gene technology pushes the application of precision medicine in patients with Fabry disease. As a milestone in the specific treatment of Fabry disease, enzyme replacement therapy can delay disease progression and improve quality of life, but not all carriers with GLA mutation need intervention immediately, and indeed individualized treatment is required. However, enzyme-enhanced therapy is only suitable for "amenable mutations" and has clinical application limitation. Therefore, new treatments such as substrate reduction therapy, second-generation enzyme replacement therapy, and gene therapy are already undergoing clinical trials, expected to bring new gospel to Fabry disease patients. This article will review development of precision treatment on Fabry disease, providing the basis of individualized treatment for the drug selection and prevention of side effect. The expectation is to drive future therapeutic strategies toward precision-based treatment.

Research progress on the definition of intermediate risk factors and postoperative adjuvant therapy for early cervical cancer / 中华放射肿瘤学杂志

Cervical cancer is still a common gynecolgical tumor in China. Radical surgery is often the first choice for the treatment of early stage cervical cancer (FIGO stage ⅠB-ⅡA), and postoperative pathological examination often has adverse prognostic factors affecting the survival. According to the NCCN guidelines, patients with cervical cancer who meet Sedlis criteria and have intermediate-risk factors (lymphatic vascular space involvement, tumor size or deep interstitial infiltration) are recommended to receive concurrent chemotherapy with postoperative pelvic external irradiation ± cisplatin. However, the diagnostic criteria, indications and methods of adjuvant therapy for patients with intermediate risk factors after early cervical cancer surgery are still controversial. In this article, research progress on the definition of intermediate risk factors for early cervical cancer after radical hysterectomy and adjuvant treatment was mainly reviewed.

Slowing the progression of myopia with the optical defocus strategies / 国际眼科杂志(Guoji Yanke Zazhi)

@#Myopia is a common ocular disorder. In recent years, the incidence of myopia presents an increasing trend year by year. Patients with high myopia are at an increased risk for severe visual impairment. The economic and societal impacts of complication associated with myopia are enormous. Therefore, it is essential and imminent for implementing effective myopia control strategies. The results of the current study suggest that uncontrolled axial elongation produced by periphral hyperopic defocus could be one of the possible mechanisms for myopia development, multiple strategies especially optical defocus technology based on this are increasingly becoming part of the mainstream clinical practice in myopia management. This article reviews the principle of optical defocus on myopia control, experimental research on defocus myopia animals, and the latest clinical applications of different optical defocus technologies on myopia control, summarizes the clinical research results of myopia control using progressive addition spectacle lenses, peripheral defocus spectacle lenses, defocus incorporated multiple segments spectacle lenses, orthokeratology contact lenses and multifocal soft contact lenses. It is proposed to provide a new option for the treatment plan to delay the progression of myopia.

Exploration and practice of multiple campuses of one hospital for public hospitals / 中华医院管理杂志

The construction of multiple campuses of one public hospital is an effective way to enlarge supply of high-quality medical resources. On the basis of sorting out the key and difficult problems faced in " multiple campuses" , People′s Hospital of Zhengzhou took " integrated management, homogeneous service, joint logistics support, and high quality development" as the main goal. It followed the guidelines of " Party committee taking overall charge, headquarters taking charge of building, campuses taking charge of routine operations, and orchestrated logistics support" . The hospital took the tactics of " collaborative oriented homogenization management" and " demand oriented and differentiated hospital positioning and discipline layout" . The practice and effect of the hospital included building multiple campuses in terms of management system, medical quality system, outstanding service system, personnel management system, cost management system, cultural construction system, and information management system. By such measures, the hospital has scientifically determined its orientation and discipline layout of every campus, hence offering references for the establishment and management model of " multiple campuses" at public hospitals at large.

The effect of different body positions after pars plana vitrectomy and inert gas filling for rhegmatogenous retinal detachment / 中华眼底病杂志

Objective:To compare and observe the curative effect of different body positions after pars plana vitrectomy (PPV) combined with inert gas filling for rhegmatogenous retinal detachment (RRD).Methods:A retrospective clinical study. From October 2019 to September 2021, 192 eyes of 192 RRD patients who were diagnosed and received PPV combined with inert gas filling in Qingdao Eye Hospital of Shandong First Medical University were included in the study. Best corrected visual acuity (BCVA), intraocular pressure, ultra-wide-angle fundus photography, optical coherence tomography, and B-mode ultrasonography were performed in all affected eyes. The BCVA examination was performed using a standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. According to the post-operative position requirements, the affected eyes were divided into the face-down positioning group and the adjustable positioning group, with 97 eyes in 97 patients and 95 eyes in 95 patients, respectively. Age ( Z=0.804), course of disease ( Z=-0.490), eye type ( χ2=0.175), logMAR BCVA( Z=-0.895), intraocular pressure ( Z=0.178), lens status ( χ2=1.090), number of detached clocks ( Z=0.301) and macular involvement ( χ2=0.219), number of holes ( Z=-1.051) and number of lower holes ( χ2=0.619) were compared, there was no significant difference ( P>0.05). The gender composition ratio was compared, and the difference was statistically significant ( χ2=5.341, P<0.05). The follow-up time after surgery was more than 3 months. The retinal reattachment rate in one operation, the improvement of BCVA and the incidence of complications were observed. The independent sample Mann-Whitney test was used for the comparison of continuous variables between groups; the χ2 test was used for the comparison of categorical variables. Results:In the face-down positioning group and the adjustable positioning group, retinal reattachment in one operation was performed in 92 (94.8%, 92/97) and 89 (93.7%, 89/95) eyes, respectively; logMAR BCVA was 0.45±0.34, 0.41±0.21. There was no significant difference in the retinal reattachment rate in one operation ( χ2=0.120, P=0.729) and logMAR BCVA ( Z=-0.815, P=0.416) between the two groups. After surgery, the intraocular pressure increased in 11 (11.3%, 11/97) and 5 (5.3%, 5/95) eyes in the face-down positioning group and the adjustable positioning group, respectively; the secondary epimacular membrane was 2 (2.1%, 2/97), 3 (3.2%, 3/95) eyes. There was no significant difference in the incidence of elevated intraocular pressure and secondary epimacular membrane between the two groups after surgery ( χ2=2.320, 0.227; P=0.128, 0.634). Conclusion:It is safe and effective to adopt adjustable positioning after PPV combined with inert gas filling for RRD, which is equivalent to the effect of face-down positioning.

Research on lightweight model of intelligent-assisted diagnosis of common fundus diseases based on fundus color photography / 中华眼底病杂志

Objective:To observe the diagnostic value of six classification intelligent auxiliary diagnosis lightweight model for common fundus diseases based on fundus color photography.Methods:A applied research. A dataset of 2 400 color fundus images from Nanjing Medical University Eye Hospital and Zhejiang Mathematical Medical Society Smart Eye Database was collected, which was desensitized and labeled by a fundus specialist. Of these, 400 each were for diabetic retinopathy, glaucoma, retinal vein occlusion, high myopia, age-related macular degeneration, and normal fundus. The parameters obtained from the classical classification models VGGNet16, ResNet50, DenseNet121 and lightweight classification models MobileNet3, ShuffleNet2, GhostNet trained on the ImageNet dataset were migrated to the six-classified common fundus disease intelligent aid diagnostic model using a migration learning approach during training as initialization parameters for training to obtain the latest model. 1 315 color fundus images of clinical patients were used as the test set. Evaluation metrics included sensitivity, specificity, accuracy, F1-Score and agreement of diagnostic tests (Kappa value); comparison of subject working characteristic curves as well as area under the curve values for different models.Result:Compared with the classical classification model, the storage size and number of parameters of the three lightweight classification models were significantly reduced, with ShuffleNetV2 having an average recognition time per sheet 438.08 ms faster than the classical classification model VGGNet16. All 3 lightweight classification models had Accuracy > 80.0%; Kappa values > 70.0% with significant agreement; sensitivity, specificity, and F1-Score for the diagnosis of normal fundus images were ≥ 98.0%; Macro-F1 was 78.2%, 79.4%, and 81.5%, respectively.Conclusion:The intelligent assisted diagnosis of common fundus diseases based on fundus color photography is a lightweight model with high recognition accuracy and speed; the storage size and number of parameters are significantly reduced compared with the classical classification model.

Spine curvature and the cardiopulmonary exercise endurance of adolescents with idiopathic scoliosis / 中华物理医学与康复杂志

Objective:To quantify any correlation between the severity of spinal curvature of an adolescent with idiopathic scoliosis and their cardiopulmonary exercise endurance.Methods:The cardiopulmonary exercise test (CPET) results and the full-length spinal X-rays in a standing position of 64 adolescents with idiopathic scoliosis were reviewed retrospectively. Independent t-tests were used to compare the two datasets obtained from those with left or right thoracic scoliosis. The correlation between the Cobb angle and cardiopulmonary exercise endurance was analyzed using Pearson correlation coefficients, multiple factor linear regression and two-stage linear regression.Results:After adjusting for gender, age, height and weight, the multiple linear regression analysis showed that the Cobb angle was significantly negatively correlated with maximum tidal volume (β=-0.013) and significantly positively correlated with the rate of respiration (β=0.421). The relationship between the Cobb angle and cardiopulmonary exercise endurance was non-linear. With a Cobb angle > 34°, a 1° increase reduces cardiopulmonary exercise endurance by a factor of 1.4 on average. At smaller Cobb angles the corresponding increase is about 0.87 times.Conclusions:The Cobb angle is a negative predictor of ventilation during exercise among adolescents with idiopathic scoliosis. The more severe a patient′s spinal curvature, the lower the cardiopulmonary exercise endurance is likely to be.

Treatment of Diabetic Nephropathy from Collateral Diseases： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is classified into "collateral diseases" in traditional Chinese medicine （TCM）. This study reviewed， analyzed， and discussed the clinical and basic research on DN treatment from collateral diseases in recent years. The main TCM therapeutic principles of DN from collateral diseases are dominated by reinforcing the deficiency and dredging collaterals. Fundamental research showed that the relevant mechanism is related to the improvement of oxidative stress and endoplasmic reticulum stress， reduction of inflammatory responses， coping with microcirculation disorder and vascular endothelial damage， and alleviation of renal injury. The theory of collateral diseases can provide ideas for clinical and basic research on DN and also shows advantages in clinical application. However， the present clinical application of this therapeutic principle is mainly based on the combination of deficiency-reinforcing drugs and blood stasis-resolving drugs. In spite of some overlap， blood stasis syndrome and collateral diseases are not in the same category. Therefore， the current diagnosis and treatment of DN from collateral diseases fail to combine with the changes of collateral vessels， main pathogenic factors， and the changes of the secondary pathogenesis. The application of classic collateral drugs such as pungent drugs， rattan drugs， and insect drugs has not been paid enough attention in syndrome differentiation and treatment. In addition， there is a lack of correlation with clinical symptoms and laboratory indexes in the basic research on the treatment of DN by Chinese medicinal prescriptions. Accordingly， the present study advocates systematic research on DN under the guidance of collateral diseases theory， clarifying the essence of DN in collateral diseases and emphasizing the importance of collateral drugs and microscopic syndrome differentiation in screening target drugs for DN to explore the underlying mechanism of collateral drugs in the treatment of DN， so as to provide evidence for the clinical application of collateral diseases theory and Chinese medicinal prescriptions against collateral diseases in the treatment of DN.

Overweight and obesity status among children in Beijing and Tokyo and its relationship with lifestyle / 中国学校卫生

Objective@#To describe the status quo of overweight and obesity among children aged 3 to 5 in Beijing and Tokyo, and to explore its relationship with lifestyle.@*Methods@#Using the method of cluster stratified random sampling, a sample of 444 children aged 3-5 years from Beijing and Tokyo were selected in Oct. and Nov. of 2019. Height, weight and lifestyle were measured. Overweight and obesity among children in the two cities and its relationship with lifestyle were compared and analyzed.@*Results@#Average level of BMI, rate of overweight and obesity of children in Beijing(25.28%) were higher than those in Tokyo( 18.44 %). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with physical activity before breakfast( χ 2=29.14, 31.18, P <0.05). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with different snack frequency after dinner( χ 2=24.72, 21.93, P <0.05). Logistic regression analysis further showed that children s lack of physical activity before breakfast in Beijing is positively related to overweight and obesity( OR= 1.45, 95%CI =1.10-2.68). Beijing children who often eat snacks after supper ( OR=2.56, 95%CI =1.44-3.57,) and sometimes eat snacks were positively correlated with the occurrence of overweight or obesity ( OR=1.72, 95%CI =1.21-2.72).@*Conclusion@#The prevalence of overweight and obesity among preschool children in Beijing is higher than that in Tokyo. Potential risk factors for overweight and obesity among infants in Beijing include lack of physical activity before breakfast and frequent snacking after dinner.

Pollution characteristics and health risk assessment of major air pollutants in Yinchuan City / 公共卫生与预防医学

Objective To understand the characteristics of environmental air pollution in three districts, two counties and one city of Yinchuan in 2020, to evaluate the air quality and the impact of air pollutants on population health, and to provide a theoretical basis for fine management of atmospheric environment in Yinchuan. Methods Based on the air pollution situation in districts and counties of Yinchuan in 2020, the air pollution characteristics were analyzed and summarized using Excel and SPSS 23.0 software. The health risks of SO2, NO2, PM10 and PM2.5 in the air were estimated using the health risk model recommended by the US Environmental Protection Agency. Results The average annual concentrations of PM10 and PM2.5 (except for Lingwu City) in all counties of Yinchuan in 2020 were higher than the national standard, while the average annual concentrations of SO2, NO2, CO and O3 in all regions were lower than the national secondary standard, indicating that the pollution level was low. Both ambient air quality and atmospheric pollutants (except O3) showed a “V” emission trend of less in summer and more in winter, while O3 was the opposite. The average annual concentrations of PM10, PM2.5, SO2 and O3 decreased from north to south, while the concentrations of NO2 and CO in Xingqing District, Xixia District and Jinfeng District were significantly higher than those in other regions. O3, NO2 and particulate matter were the primary atmospheric pollutants in the study area. The health risks of PM10, PM2.5, SO2 and O3 did not exceed the values recommended by the US Environmental Protection Agency. However, these air pollutants posed the greatest health risk to children, while the health risk to the elderly was the least. There were differences in the health risks of these air pollutants between men and women of different ages. Among children and young adults, the health risk for men was higher than that for women. Among adolescent people and the elderly, the health risk of females was obviously higher than that of males. Conclusion The air quality in Yinchuan is good, and the health risk of the population is low.

Preparation and identification of antibodies targeting influenza A virus N1 subtype neuraminidase / 中华微生物学和免疫学杂志

Objective:To prepare and identify a functional antibody FNA1 targeting the neuraminidase (NA) of influenza A virus N1 subtype.Methods:According to single-chain antibody fragment (scFv) sequence, the heavy chain and light chain variable region sequences of FNA1 were synthesized, and the recombinant expression plasmid pFRT-IgG1κ-FNA1 was constructed by linking the expression vector pFRT-IgG1κ. The FNA1 antibody was expressed in ExpiCHO cells and purified using affinity purification technique. The binding ability of FNA1 to the target proteins, influenza A virus N1 subtype NA antigens, was detected by ELISA. Flow cytometry was performed to analyze the binding ability of FNA1 to the NA antigens expressed on the surface of cell membrane. The in vitro activity of FNA1 against NA was evaluated by infecting 293T cells with pseudovirus. Results:Protein electrophoresis showed that FNA1 with high purity was obtained. FNA1 specifically recognized and bound to N1 subtype NA antigens in a concentration-dependent manner. FNA1 could effectively block NA activity by binding to N1 subtype NA protein expressed on the surface of cell membrane, thus inhibiting the release of packaged pseudovirus from cell surface and further inhibiting target cell infection.Conclusions:An antibody FNA1 targeting influenza A virus N1 subtype NA with in vitro functional activity was obtained.

Preparation and identification of a broad-spectrum antibody targeting hemagglutinin protein of influenza A virus / 中华微生物学和免疫学杂志

Objective:To prepare and identify a broad-spectrum antibody FHA3 targeting influenza A virus hemagglutinin (HA).Methods:According to the single-chain antibody fragment (scFv) sequence, the heavy chain (VH) and light chain (VL) variable regions of FHA3 were amplified by PCR and a recombinant plasmid pFRT-IgG1κ-FHA3 was constructed by linking the expression vector pFRT-IgG1κ. FHA3 was expressed in the ExpiCHO system and purified by affinity purification. The binding activity of FHA3 to influenza A virus HA was detected by ELISA. The neutralizing activity of FHA3 was detected in vitro by infecting host cells with pseudovirus. Results:SDS-PAGE showed that high-purity FHA3 was obtained. FHA3 could bind to H1N1 HA, H2N2 HA, H3N2 HA, H5N1 HA, H7N9 HA and H9N2 HA in a concentration-dependent manner. FHA3 had good neutralizing activity in vitro that was it could effectively block the invasion of H5N1 and H7N9 pseudoviruses into target cells at a low concentration of 5 μg/ml and H1N1 pseudovirus at 0.012 5 μg/ml. Conclusions:A broad spectrum antibody targeting HA protein of influenza A virus with neutralizing activity in vitro was obtained.

Progress in cross reactivity of neutralizing monoclonal antibodies against dengue virus / 中华微生物学和免疫学杂志

Neutralizing monoclonal antibodies against dengue virus cross-react with other flaviviruses due to the sequence homology between them, such as the antibodies targeting envelope protein and non-structural protein 1. Apart from exerting protective effects in infected animals, cross-neutralizing antibodies could also cause antibody-dependent enhancement (ADE) in vivo. This review summarized the progress in cross-reactivity of neutralizing antibodies against dengue virus.