Electrophysiologic Characteristics of Nitrous-Oxide-Associated Peripheral Neuropathy:A Retrospective Study of 76 Patients

Background@#and Purpose The electrophysiologic characteristics of peripheral neuropathy secondary to nitrous oxide (N2O) abuse remain unclear. The paper therefore aimed to summarize the electrophysiologic characteristics of N2O-associated peripheral neuropathy and identify the risk factors of severe nerve injury. @*Methods@#The electrophysiologic results and clinical data of patients with peripheral neuropathy secondary to N2O abuse at our hospital between 2018 and 2020 were analyzed retrospectively, and their electrophysiologic changes were summarized. @*Results@#Most patients exhibited decreased sensory and motor nerve conduction velocities (75% and 76%), decreased sensory nerve and compound motor action potentials (57% and 59%), and prolonged distal motor latency (59%), while a response was absent in 36%. These findings indicate that N2O abuse can result in generalized injury to sensory and motor nerves. Electrophysiologic results indicated axonal neuropathy in 37 cases (49%), demyelinating peripheral neuropathy in 4 (5%), and mixed neuropathy in 12 (16%). Peripheral nerve injury was more common in the lower limbs (72%) than in the upper limbs (42%, p<0.0001). The upper and lower limbs were primarily affected by sensory nerve demyelination (35%) and motor axonal injury (67%), respectively. Subgroup analysis indicated that longer N2O exposure and longer disease course were associated with more-severe motor axonal injury in the lower limbs. @*Conclusions@#N2O-associated peripheral neuropathy can lead to sensory and motor nerve injury, with axonal injury being the most common. Injuries were more severe in the lower limbs. Prolonged N2O exposure and disease course increased the severity of motor axonal injury in the lower limbs.

Modification of C20 oxidase in tanshinone biosynthesis pathway / 中国中药杂志

Tanshinones are one of the main effective components of Salvia miltiorrhiza, which play important roles in the treatment of cardiovascular diseases. Microbial heterogony production of tanshinones can provide a large number of raw materials for the production of traditional Chinese medicine(TCM) preparations containing S. miltiorrhiza, reduce the extraction cost, and relieve the pressure of clinical medication. The biosynthetic pathway of tanshinones contains multiple P450 enzymes, and the catalytic element with high efficiency is the basis of microbial production of tanshinones. In this study, the protein modification of CYP76AK1, a key P450-C20 hydroxylase in tanshinone pathway, was researched. The protein modeling methods SWISS-MODEL, Robetta, and AlphaFold2 were used, and the protein model was analyzed to obtain the reliable protein structure. The semi-rational design of mutant protein was carried out by molecular docking and homologous alignment. The key amino acid sites affecting the oxidation activity of CYP76AK1 were identified by molecular docking. The function of the obtained mutations was studied with yeast expression system, and the CYP76AK1 mutations with continuous oxidation function to 11-hydroxysugiol were obtained. Four key amino acid sites that affected the oxidation acti-vity were analyzed, and the reliability of three protein modeling methods was analyzed according to the mutation results. The effective protein modification sites of CYP76AK1 were reported for the first time in this study, which provides a catalytic element for different oxidation activities at C20 site for the study of the synthetic biology of tanshinones and lays a foundation for the analysis of the conti-nuous oxidation mechanism of P450-C20 modification.

Advances in research methods for biosynthetic pathway analysis of active ingredients in traditional Chinese medicine / 中国中药杂志

The active ingredients in traditional Chinese medicine(TCM)are the foundation for the efficiency of TCM and the key to the formation of Dao-di herbs. It is of great significance to study the biosynthesis and regulation mechanisms of these active ingredients for analyzing the formation mechanism of Daodi herbs and providing components for the production of active ingredients in TCM by synthetic biology. With the advancements in omics technology, molecular biology, synthetic biology, artificial intelligence, etc., the analysis of biosynthetic pathways for active ingredients in TCM is rapidly progressing. New methods and technologies have promoted the analysis of the synthetic pathways of active ingredients in TCM and have also made this area a hot topic in molecular pharmacognosy. Many researchers have made significant progress in analyzing the biosynthetic pathways of active ingredients in TCM such as Panax ginseng, Salvia miltiorrhiza, Glycyrrhiza uralensis, and Tripterygium wilfordii. This paper systematically reviewed current research me-thods for analyzing the biosynthetic functional genes of active ingredients in TCM, elaborated the mining of gene elements based on multiomics technology and the verification of gene functions in plants in vitro and in vivo with candidate genes as objects. Additionally, the paper summarized new technologies and methods that have emerged in recent years, such as high-throughput screening, molecular probes, genome-wide association studies, cell-free systems, and computer simulation screening to provide a comprehensive reference for the analysis of the biosynthetic pathways of active ingredients in TCM.

Advances on the microbial synthesis of plant-derived diterpenoids / 生物工程学报

Natural plant-derived diterpenoids are a class of compounds with diverse structures and functions. These compounds are widely used in pharmaceuticals, cosmetics and food additives industries because of their pharmacological properties such as anticancer, anti-inflammatory and antibacterial activities. In recent years, with the gradual discovery of functional genes in the biosynthetic pathway of plant-derived diterpenoids and the development of synthetic biotechnology, great efforts have been made to construct a variety of diterpenoid microbial cell factories through metabolic engineering and synthetic biology, resulting in gram-level production of many compounds. This article summarizes the construction of plant-derived diterpenoid microbial cell factories through synthetic biotechnology, followed by introducing the metabolic engineering strategies applied to improve plant-derived diterpenoids production, with the aim to provide a reference for the construction of high-yield plant-derived diterpenoid microbial cell factories and the industrial production of diterpenoids.

Recent progress in aptamer-based microfluidics for the detection of circulating tumor cells and extracellular vesicles / 药物分析学报

Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circu-lating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based micro-fluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

Effect of titanium plate internal fixation combined with titanium nail intermaxillary traction on jaw fractures / 中华医学美学美容杂志

Objective:To observe the difference in the effect of simple titanium plate internal fixation and titanium plate internal fixation combined with titanium nail intermaxillary traction in the treatment of jaw fractures and their impact on the oral and maxillofacial function of patients.Methods:From August 2016 to May 2021, 94 patients with jaw fractures admitted to the Department of Stomatology, Linyi Central Hospital, Shandong (supplementing the gender, age range and average age of the patients), were divided into 47 cases in the control group, and the titanium plates were used alone, combined operation group 47 cases, titanium plate internal fixation combined with intermaxillary traction with titanium nails. The changes of oral and maxillofacial function and fracture healing were measured before operation and 3 months after operation, and the perioperative indicators and postoperative complications were recorded.Results:Three months after operation, the scores of maxillofacial function, mouth function and masticatory function in the combined operation group (0.52±0.09 points, 0.67±0.12 points, 0.58±0.08 points) were significantly lower than those in the control group (1.05±0.21 points, 1.14±0.22 points, 1.02±0.21 points) ( t=15.90, 12.86, 13.42, P<0.05). The effective rate of the combined operation group was 95.74% (45/47), which was significantly higher than that of the control group (80.85%, 38/47) (χ 2=5.05, P<0.05); there was no significant difference in operation time and hospitalization time between the groups ( P>0.05), the fracture healing time in the combined surgery group (65.02±7.06) d was significantly shorter than that in the control group (82.69±10.25) d ( t=9.73, P<0.05). The postoperative complication rate of combined treatment group was 6.38% (3/47), which was significantly lower than the control group 21.28% (10/47) (χ 2=4.37, P<0.05). Conclusions:In the treatment of jaw fractures, titanium plate internal fixation combined with titanium nail intermaxillary traction treatment can significantly improve the oral and maxillofacial function of patients, promote postoperative fracture healing, improve curative effect and reduce the incidence of complications compared with simple titanium plate internal fixation.

Isolation, culture and validation of CD34+ vascular wall-resident stem cells from mice / 生理学报

Vascular wall-resident stem cells (VW-SCs) play a critical role in maintaining normal vascular function and regulating vascular repair. Understanding the basic functional characteristics of the VW-SCs will facilitate the study of their regulation and potential therapeutic applications. The aim of this study was to establish a stable method for the isolation, culture, and validation of the CD34+ VW-SCs from mice, and to provide abundant and reliable cell sources for further study of the mechanisms involved in proliferation, migration and differentiation of the VW-SCs under various physiological and pathological conditions. The vascular wall cells of mouse aortic adventitia and mesenteric artery were obtained by the method of tissue block attachment and purified by magnetic microbead sorting and flow cytometry to obtain the CD34+ VW-SCs. Cell immunofluorescence staining was performed to detect the stem cell markers (CD34, Flk-1, c-kit, Sca-1), smooth muscle markers (SM22, SM MHC), endothelial marker (CD31), and intranuclear division proliferation-related protein (Ki-67). To verify the multipotency of the isolated CD34+ VW-SCs, endothelial differentiation medium EBM-2 and fibroblast differentiation medium FM-2 were used. After culture for 7 days and 3 days respectively, endothelial cell markers and fibroblast markers of the differentiated cells were evaluated by immunofluorescence staining and q-PCR. Furthermore, the intracellular Ca2+ release and extracellular Ca2+ entry signaling were evaluated by TILLvisION system in Fura-2/AM loaded cells. The results showed that: (1) High purity (more than 90%) CD34+ VW-SCs from aortic adventitia and mesenteric artery of mice were harvested by means of tissue block attachment method and magnetic microbead sorting; (2) CD34+ VW-SCs were able to differentiate into endothelial cells and fibroblasts in vitro; (3) Caffeine and ATP significantly activated intracellular Ca2+ release from endoplasmic reticulum of CD34+ VW-SCs. Store-operated Ca2+ entry (SOCE) was activated by using thapsigargin (TG) applied in Ca2+-free/Ca2+ reintroduction protocol. This study successfully established a stable and efficient method for isolation, culture and validation of the CD34+ VW-SCs from mice, which provides an ideal VW-SCs sources for the further study of cardiovascular diseases.

Clinical characteristics and genetic analysis of 6 cases of neonatal diabetes mellitus / 中国新生儿科杂志

Objective:To study the clinical features, genetic characteristics and prognosis of neonatal diabetes mellitus (NDM).Methods:From January 2015 to January 2022, neonates with NDM admitted to the Department of Neonatology of our hospital were retrospectively reviewed.Their clinical manifestations, biochemical data, genetic tests, treatments and outcomes were analyzed.Results:A total of 6 cases with NDM were included, with 3 males and 3 females. All 6 cases were full-term infants, 5 were low birth weight infants and 1 had family history of diabetes. High blood glucose were found on 1~11 d (average 4 d) after birth. 3 cases were diagnosed during blood glucose screening for low birth weight and 3 cases were diagnosed due to infection and/or diabetic ketoacidosis. Blood C-peptide levels were below normal range in all 6 cases. Blood insulin levels were decreased in 5 cases and remained at the lower limit of normal range in 1 case. All infants received genetic tests and 4 showed abnormal results, including 2 cases of ABCC8 gene mutation [c.2060C>T (p.T687M), not reported; c.674T>C (p.L225P), reported], 1 case of KCNJ11 gene mutation [c.602G>A (p.Arg201His), not reported] and 1 case of paternal uniparental disomy (UPD)6q24 (reported). All 6 cases were treated with insulin. Glibenclamide was experimented to replace insulin in 3 cases and 1 case was successful. During follow-up (at the age 4 months~5 years old), 4 cases were diagnosed with transient NDM, 1 case with permanent NDM and 1 case died at the age of 4 months without classification. 1 case showed psychomotor and language delay and the others had otherwise normal development.Conclusions:Most NDM infants are low birth weight infants with reduced blood insulin and C-peptide.Transient NDM are common. Proactive genetic testing may help treatment.

Loss of ATM activity induces GADD45α-dependent apoptosis in cerebellar granular neurons / 中山大学学报(医学科学版)

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.

Effects of titanium dioxide nanoparticles on circRNA expression profiles in human hepatocellular carcinoma cells HepG2 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of titanium dioxide nanoparticles (TiO2 NPs) on the expression profile of circular ribonucleic acid (circRNA) in human hepatocytes through in vitro cell experiments, and to attempt to understand the potential mechanism of hepatotoxicity through bioinformatics analysis.@*METHODS@#TiO2 NPs were characterized from the aspects of particle size, shape and agglomeration state. The cell counting kit-8 (CCK8) was used to detect the cytotoxicity of TiO2 NPs against human hepatocellular carcinoma cells (HepG2) after exposure to 0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100, and 200 mg/L TiO2 NPs for 24 h or 48 h. The cells were treated at doses of 0 mg/L TiO2 NPs (control group) and 100 mg/L TiO2 NPs (treatment group), and collected after exposure for 48 h, and then RNA from the extracted cell samples was collected and sequenced. The differential circRNAs between the control and the TiO2 NPs treatment groups were screened, and then the enrichment pathway of the differential circRNA target gene was analyzed by multivariate statistics. According to the sequencing results, significantly altered genes and important genes in the significant enrichment pathways were screened, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) was performed to verify the results.@*RESULTS@#TiO2 NPs were spherical anatase with a hydrated particle size of (323.50±85.44) nm and a Zeta potential of (-21.00±0.72) mV in a serum-free medium. The results of the CCK8 cytotoxicity assay showed that with the increase of TiO2 NPs concentration, cell viability gradually decreased. A total of 11 478 circRNAs were found by RNA sequencing. Compared with the control groups, TiO2 NPs treatment groups (100 mg/L) had a total of 89 differential circRNAs, of which 59 were up-regulated and 30 were down-regulated. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the targeted genes of differential circRNAs were mainly enriched in fatty acid degradation, Fanconi anemia pathway, and fatty acid metabolism. The expression levels of circRNA.6730, circRNA.3650 and circRNA.4321 were significantly different between the TiO2 NPs treatment group and the control group, which were consistent with the sequencing results.@*CONCLUSION@#TiO2 NPs can induce changes in circRNA expression profile, and epigenetics may play an important role in the mechanism of hepatotoxicity.

Analysis of the direct economic burden of measles cases and its influencing factors in Shanghai from 2017 to 2019 / 中华预防医学杂志

Objective: To analyze the direct economic burden caused by measles cases in Shanghai from 2017 to 2019 and its influencing factors. Methods: A total of 161 laboratory-confirmed measles cases reported from January 1, 2017, to December 31, 2019, in Shanghai were included in the study through the "Measles Surveillance Information Reporting and Management System" of the "China Disease Surveillance Information Reporting and Management System". Through telephone follow-up and consulting hospital data, the basic information of population, medical treatment situation, medical treatment costs and other information were collected, and the direct economic burden of cases was calculated, including registration fees, examination fees, hospitalization fees, medical fees and other disease treatment expenses, as well as transportation and other expenses of cases. The multiple linear regression model was used to analyze the main influencing factors of the direct economic burden. Results: The age of 161 measles cases M (Q1, Q3) was 28.21 (13.33, 37.00) years. Male cases (56.52%) were more than female cases (43.48%). The largest number of cases was≥18 years old (70.81%). The total direct economic burden of 161 measles cases was 540 851.14 yuan, and the per capita direct economic burden was 3 359.32 yuan. The direct economic burden M (Q1, Q3) was 873.00 (245.01, 4 014.79) yuan per person. The results of multiple linear regression model analysis showed that compared with other and unknown occupations, central areas and non-hospitalized cases, the direct economic burden of measles cases was higher in scattered children, childcare children, students, and cadre staff in the occupational distribution, suburban areas and hospitalized, with the coefficient of β (95%CI) values of 0.388 (0.150-0.627), 0.297 (0.025-0.569), 0.327 (0.148-0.506) and 1.031 (0.853-1.209), respectively (all P values<0.05). Conclusion: The direct economic burden of some measles cases in Shanghai is relatively high. Occupation, area of residence and hospitalization are the main factors influencing the direct economic burden of measles cases.

Research on rapid detection technology of airborne pathogenic organisms based on up-conversion phosphor technology / 中华预防医学杂志

Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 107 CFU/ml and 108 CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 104 CFU/ml. Detection sensitivity of Yersinia pestis ≥103 CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥103 CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 104 CFU/m3, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.

Efficacy of optimal pulse technology in the treatment of demodex blepharitis and its effect on ocular surface function / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of optimal pulse technology(OPT)in the treatment of demodex blepharitis and its influence on ocular surface function.METHODS: A retrospective study was conducted from February 2018 to October 2020. A total of 127 patients(254 eyes)with demodex blepharitis were assigned to the observation group and the control group according to the treatment method. The control group(63 patients, 126 eyes)were given conventional hot compress, eye cleansing and drug therapy. On this basis, the observation group(64 patients, 128 eyes)was treated with OPT. Both groups were given 6wk of continuous treatment. Demodex count, Marx's line scores, meibum character scores, ocular surface disease index(OSDI)scores, non-invasive tear break-up time(NIBUT), non-invasive tear meniscus height(NITMH)and lipid layer thickness(LLT)were compared between the two groups, and safety was evaluated.RESULTS: After 6wk of treatment, demodex count, Marx's line scores, meibum character scores and OSDI scores of the two groups decreased. NIBUT, NITMH and LLT increased. Meanwhile, demodex count, Marx's line scores, meibum character scores and OSDI scores of the observation group were significantly lower than those in the control group. NIBUT, NITMH and LLT were longer/larger than those in the control group(P<0.001). No obvious abnormality of intraocular pressure or conjunctival/corneal injury was observed in either group.CONCLUSION:OPT is effective and safe in the treatment of demodex blepharitis.

Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression / 老年心脏病学杂志（英文版）

BACKGROUND@#Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood.@*METHODS@#Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.@*RESULTS@#In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.@*CONCLUSIONS@#CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Analysis of teaching difficulties in the chapter of antigen in Medical Immunology and teaching strategy / 细胞与分子免疫学杂志

The concept of "ntigen"is a relative one. The narrow concept of it condenses the process of activation of adaptive immune response and re-recognition of the same antigen, revealing the protective mechanism of vaccines with great significance for research and development of vaccines. However, the narrow concept involves adaptive immune system members: B cells, T cells and their effector products, which is difficult for beginners to understand the inherent meaning. Meanwhile, antigen classification fully summarizes the immune response process, so a variety of classification approach increases the difficulty in learning. Our teaching team analyzes the difficulties of this chapter in depth, and we implements the strategy that takes antibody structure and function as the breakthrough point and simplified adaptive immune response process as the core in teaching. A mind map that includes the main contents of this chapter is made during the process, which promotes the effectiveness of classroom teaching greatly.

Distribution of monocyte subsets and their surface CD31 intensity are associated with disease course and severity of hemorrhagic fever with renal syndrome / 细胞与分子免疫学杂志

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14++CD16-), intermediated monocyte subsets (CD14++CD16+) and non-classical monocyte subsets (CD14+CD16++) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.

Research progress in antisense drug mechanism and chemical modification strategies / 药学学报

Over the past three decades, more and more antisense drugs have been approved for marketing or clinical trails. Antisense technology has become the focus of pharmaceutical research due to its unique advantages in treating diseases and strong clinical development potential. There is a big difference from traditional small molecule chemical drugs, and macromolecular protein biological drugs. Antisense drugs are a very independent drug form. Antisense drugs were initially used to treat diseases with single gene mutations, but recently they have gradually begun to be used for the treatment of common diseases. Rational antisense drug design is crucial for disease treatment based on genetics. This paper reviews the latest progress in the field of action mechanism, chemical modification and delivery strategy of antisense drugs, and analyzes the current intractable problems. It is believed that with the resolution of these problems, the research of antisense drugs can reach a new level.

Association between sleep duration and social anxiety in children and adolecsents / 中国学校卫生

Objective@#To analyze the association between sleep duration and social anxiety in Chinese children and adolescents to provide evidence for promoting healthy lifestyle and mental health in children and adolescents.@*Methods@#A total of 1 145 children and adolescents aged 7-16 were recruited by cluster random sampling in Beijing in 2020, and received a series of body measurements and questionnaire survey. Social Anxiety Scale for Children (SASC) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the social anxiety symptoms and sleep duration of children and adolescents. T test was used to compare the differences of social anxiety level in different groups, and multivariate linear regression analysis was used to analyze the relationship between sleep duration and social anxiety.@*Results@#The average score of social anxiety was (5.47±4.18). The social anxiety score of girls, participants aged 13-16, with insufficient physical activity and insufficient sleep duration were higher ( t =-4.34, -6.14, 3.35, 2.93, P < 0.05). The results of multivariate linear regression model showed that after adjusting confounding factors, social anxiety decreased by 0.78 for each additional hour of sleep duration ( β =-0.78, 95% CI =-1.03--0.54, P <0.01), with 0.60 in boys (95% CI = -0.95 --0.25), 0.90 in girls (95% CI =-1.24--0.56), 0.75 among participants aged 7-12 (95% CI =-1.11--0.40) and 0.76 among participants aged 13~16 (95% CI =-1.11--0.41)( P <0.01), respectively. Social anxiety among participants who were not over weight or obese decreased by 0.78(95% CI =-1.09--0.48) and 0.81 among overweight and obese group (95% CI =-1.22- -0.41 )( P <0.01) for each additional hour of sleep duration, respectively.@*Conclusion@#Substantial differences in social anxiety are observed in children and adolescents by gender, age group and nutritional status. Sufficient sleep duration is significantly related to the decrease of social anxiety, and improve the overall level of student mental health.

Association between sleep duration and social anxiety in children and adolecsents / 中国学校卫生

Objective@#To analyze the association between sleep duration and social anxiety in Chinese children and adolescents to provide evidence for promoting healthy lifestyle and mental health in children and adolescents.@*Methods@#A total of 1 145 children and adolescents aged 7-16 were recruited by cluster random sampling in Beijing in 2020, and received a series of body measurements and questionnaire survey. Social Anxiety Scale for Children (SASC) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the social anxiety symptoms and sleep duration of children and adolescents. T test was used to compare the differences of social anxiety level in different groups, and multivariate linear regression analysis was used to analyze the relationship between sleep duration and social anxiety.@*Results@#The average score of social anxiety was (5.47±4.18). The social anxiety score of girls, participants aged 13-16, with insufficient physical activity and insufficient sleep duration were higher ( t =-4.34, -6.14, 3.35, 2.93, P < 0.05). The results of multivariate linear regression model showed that after adjusting confounding factors, social anxiety decreased by 0.78 for each additional hour of sleep duration ( β =-0.78, 95% CI =-1.03--0.54, P <0.01), with 0.60 in boys (95% CI = -0.95 --0.25), 0.90 in girls (95% CI =-1.24--0.56), 0.75 among participants aged 7-12 (95% CI =-1.11--0.40) and 0.76 among participants aged 13~16 (95% CI =-1.11--0.41)( P <0.01), respectively. Social anxiety among participants who were not over weight or obese decreased by 0.78(95% CI =-1.09--0.48) and 0.81 among overweight and obese group (95% CI =-1.22- -0.41 )( P <0.01) for each additional hour of sleep duration, respectively.@*Conclusion@#Substantial differences in social anxiety are observed in children and adolescents by gender, age group and nutritional status. Sufficient sleep duration is significantly related to the decrease of social anxiety, and improve the overall level of student mental health.

Clonal hematopoiesis of indeterminate potential and aging / 中华老年医学杂志

Clonal hematopoiesis with indeterminant potential(CHIP)is defined as the proportion of detectable clonal hematopoietic cells in peripheral blood exceeding 2% and without confirmed hematologic malignancy.CHIP could increase the risk of malignant diseases through changes in DNA damage response, transcriptional programming and epigenetic modification.The incidence of malignant tumors in the blood system is significantly higher in the CHIP patients than healthy person.In addition, CHIP represents a negative factor associated with aging.Recent studies have found that the incidences of infections, anemia, heart failure, thrombotic events, and tumors of the blood system in CHIP carriers were significantly increased.Starting with the epigenetic modifications, phenotypic changes and inflammatory mechanisms of CHIP-related gene mutations, this paper discussed the mechanisms of CHIP-related diseases and possible intervention aimed at aging.