Advance on anti-tumor theranostics and biosafety of bismuth-based nanomedicine / 药学学报

Nanomedicine is one of the most promising fields in biomedicine. Inorganic nanomaterials stand out among many nanomaterials due to their excellent physicochemical properties, stable chemical properties and high biocompatibility. As an inorganic nanomaterial, bismuth-based nanomaterials have the advantages of adjustable band gap, low toxicity, easy functionalization, large X-ray attenuation coefficient, high photothermal conversion efficiency and long cycle half-life, so they have good promising application in cancer diagnosis and treatment. This review summarizes the recent research progress of bismuth-based nanomaterials in tumor diagnosis, treatment and biosafety, which provides a theoretical basis for the design and exploitation of a new generation of bismuth-based nanomedicine systems.

Analysis of short-term efficacy and safety of the first subcutaneous injection of dupilumab in the treatment of moderate-to-severe childhood atopic dermatitis / 中华皮肤科杂志

Objective:To investigate short-term efficacy and safety of subcutaneous injection of dupilumab in the treatment of moderate-to-severe childhood atopic dermatitis (AD) .Methods:A retrospective study was conducted on clinical data from children who were diagnosed with moderate-to-severe AD and subcutaneously injected with dupilumab in Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from March 2021 to August 2021. Changes in the Eczema Area and Severity Index (EASI), itch Numeric Rating Scale (NRS) score, SCORing Atopic Dermatitis (SCORAD) index, and Dermatology Family quality of life Index (DFI) were analyzed before and 4 weeks after the first subcutaneous injection of dupilumab. Adverse events were collected during the first injection to the first follow-up visit at week 4 after the start of treatment. Normally distributed measurement indices were compared by using paired t test, non-normally distributed measurement indices were compared by using signed rank test, and logistic regression analysis was used to evaluate the effects of disease duration, eosinophil counts, IgE levels, personal and family history of allergic diseases on EASI50 (≥ 50% decrease in the EASI score) after dupilumab treatment. Results:A total of 39 children were enrolled in this study, including 21 males and 18 females. Twenty-one patients were aged 2 to < 6 years, 18 were aged 6 to < 18 years, and their median age ( Q1, Q3) was 65.0 (53.0, 111.0) months. Four weeks after the single-dose subcutaneous injection of dupilumab, 18 patients (84.85%) achieved ≥ 50% decrease in EASI score, 13 (60.61%) ≥ 75% decrease in EASI score; 18 (75.76%) experienced a decrease of ≥ 4 points in peak NRS, and 20 (81.82%) ≥ 3 points in peak NRS; the SCORAD score decreased by ≥ 50% in 15 (68.75%) patients, and by ≥ 75% in 7 (18.75%). Neither common adverse events such as conjunctivitis, skin infections, injection site reactions, nor serious adverse events were observed in any of the children from the first injection to the first follow-up visit at week 4. Logistic regression analysis showed no significant effect of the disease duration, eosinophil counts, IgE levels, personal or family history of allergic diseases on EASI50 (all P > 0.05) . Conclusion:A single-dose subcutaneous injection of dupilumab can markedly improve pruritus and severity of skin lesions in children with moderate-to-severe AD, and enhance the family quality of life, with favorable short-term safety.

Efficacy and Safety of the Safe Triangular Working Zone Approach in Percutaneous Vertebroplasty for Spinal Metastasis

Objective@#This study aimed to assess the technical feasibility, efficacy, and safety of the safe triangular working zone (STWZ) approach applied in percutaneous vertebroplasty (PV) for spinal metastases involving the posterior part of the vertebral body. @*Materials and Methods@#We prospectively enrolled 87 patients who underwent PV for spinal metastasis involving the posterior part of the vertebral body, with or without the STWZ approach, from January 2019 to April 2022. Forty-nine patients (27 females and 22 males; mean age ± standard deviation [SD], 57.2 ± 11.6 years; age range, 31–76 years) were included in group A (with STWZ approach), accounting for 54 vertebrae. Thirty-eight patients (18 females and 20 males; 59.1 ± 10.9 years; 29–81 years) were included in group B (without STWZ approach), accounting for 57 vertebrae. Patient demographics, procedure-related variables, and pain relief as assessed using the visual analog scale (VAS) were collected at different time points. Tumor recurrence in the vertebrae after PV was analyzed using Kaplan–Meier curves. @*Results@#The STWZ approach was successful from T1 to L5 without severe complications. Cement filling was satisfactory in 47/54 (87.0%) and 25/57 (43.9%) vertebrae in groups A and B, respectively (v< 0.001). Cement leakage was not significantly different between groups A and B (p= 1.000). Mean VAS score ± SD before and 1 week and 1, 3, 6, 9, and 12 months after PV were 7.6 ± 1.8, 4.2 ± 2.0, 2.7 ± 1.9, 1.9 ± 1.5, 1.7 ± 1.4, 1.7 ± 1.1, and 1.6 ± 1.3, respectively, in group A and 7.2 ± 1.7, 4.0 ± 1.3, 3.4 ± 1.6, 2.4 ± 1.2, 1.8 ± 1.0, 1.4 ± 0.5, and 1.7 ± 0.9, respectively, in group B. Kaplan–Meier analysis showed a lower tumor recurrence rate in group A than in group B (p = 0.001). @*Conclusion@#The STWZ approach may represent a new, safe, alternative/auxiliary approach to target the posterior part of the vertebral body in the PV for spinal metastases.

Clinical Features and Genetic Analysis of Autosomal Dominant and Recessive Hyperimmunoglobulin E Syndrome / 罕见病研究

  Objective  To summarize the clinical and genetic features of children with autosomal dominant and recessive hyperimmunoglobulin E syndrome (HIES).  Methods  HIES patients were studied at the dermatology department of Beijing Children's Hospital, Capital Medical University were collected, from January 2013 to December 2021, diagnosed by both clinical manifestation and genetic assessment. The general data were summarized, the clinical and genetic characteristics were analyzed, and the similarities and differences between autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES) were compared.  Results  A total of 7 children with HIES were studied, including 3 cases of AD-HIES and 4 cases of AR-HIES. There were 4 males and 3 females. All children had recurrent eczema-like lesions, recurrent skin and pulmonary infections, and elevated serum IgE and eosinophil levels. The differences between AD-HIES and AR-HIES mainly include: the main cutaneous infection in 3 children with AD-HIES were bacterial infections (such as abscess and impetigo), while in 4 children with AR-HIES, cutaneous infections were mostly severe viral infection (such as verruca vulgaris and molluscum contagiosum). There were pulmonary parenchymal changes (such as pneumatoceles, cyst and atelectasis) in 3 children with AD-HIES, whilst there were no similar changes in the lungs of 4 children with AR-HIES; 75% of children with AR-HIES had allergic diseases (including asthma and food allergy), while there were no reports of allergic diseases in children with AD-HIES. As for manifestations outside of immune system, AD-HIES was more likely to appear facial dysmorphism(such a broad nasal bridge and a high-arched palate). Furthermore, the incidence of tumor in AR-HIES was higher than that in AD-HIES. AD-HIES was mainly caused by the mutation of STAT3 gene, and AR-HIES was mainly caused by the mutation of DOCK8 gene. We reported two new mutation sites of DOCK8 gene c.1798-2A > T and c.874G > A in two cases, respectively.  Conclusions  For children with clinical manifestations of recurrent eczema-like lesions, repeated infection and significant increase in serum IgE levels, HIES should be suspected, and genetic screening should be carried out to make definite diagnosis and classification, to achieve better long-term management and improve prognosis.

Electroencephalogram for Patients with Post-stroke Cognitive Impairment before and after Treatment / 中国康复理论与实践

Objective:To analyze the changes of electroencephalogram (EEG) before and after treatment in patients with post-stroke cognitive impairment (PSCI). Methods:From October, 2018 to April, 2019, twelve PSCI patients received cognitive training and repetitive transcranial magnetic stimulation for six weeks. They were assessed with Mini-Mental State Examination, Montreal Cognitive Assessment and modified Barthel Index before and after treatment, while their closed-eye resting EEG were collected. Results:The scores of all the assessments improved after treatment (|t| > 3.507, P < 0.01); while alpha absolute power and alpha relative power increased (|t| > 2.522, P < 0.05), and brain symmetry index and DTABR decreased (t > 2.435, P < 0.05). Conclusion:The characteristics of EEG of PSCI patients changes with the recovery of cognitive function. Further research is needed about the relationship between EEG and cognitive function.

Mutation analysis of the ERCC2 and ERCC5 genes in two cases of xeroderma pigmentosum / 中华皮肤科杂志

Objective:To detect gene mutations in two patients with xeroderma pigmentosum (XP) .Methods:Clinical data were collected from two patients with XP. DNA was extracted from peripheral blood of the patients and their parents, and high-throughput whole-exome sequencing was performed in the patient to identify pathogenic gene mutations. Then, Sanger sequencing was performed to bidirectionally verify the mutations in the patients and their parents, with a focus on mutations in the candidate genes XPA, ERCC3, XPC, ERCC2, DDB2, ERCC4, ERCC5 and POLH.Results:Case 1, a 3-year-old male patient, presented with brown spots and hypopigmented macules on the face, ears, neck and back of both hands for 2 years, as well as gait instability for 1 year. The skin lesions were mainly distributed in sun-exposed areas and worsened in summer. Case 2, a male patient aged 1 year and 5 months, presented with scattered brown spots and a few hypopigmented macules on the face for 1 year. Genetic testing showed compound heterozygous mutations in the ERCC2 gene of case 1, including c.1805G>A (p.Gly602Asp) mutation inherited from his father and c.586C>T (p.Arg196Ter) mutation inherited from the his mother, so case 1 was diagnosed with XP group D (XPD) . Compound heterozygous mutations were identified in the ERCC5 gene of case 2, including c.2533+2T>C mutation inherited from his father and c.2453C>T (p.Ala818Val) mutation inherited from his mother, so case 2 was diagnosed with XP group G (XPG) . The c.586C>T (p.Arg196Ter) and c.2533+2T>C mutations had not been reported before. Sun protection was suggested. After a follow-up of 2 years, skin lesions increased in the 2 patients, but no malignant tumors occurred.Conclusions:The compound heterozygous mutations in the ERCC2 gene can lead to XPD, mainly manifesting as cutaneous and neurological symptoms, while the compound heterozygous mutations in the ERCC5 gene can lead to XPG, manifesting as a mild phenotype. Early clinical features combined with genetic testing are helpful for accurate diagnosis and classification of XP.

An emollient containing Prinsepia utilis Royle oil extracts and other extracts for the improvement of clinical symptoms among children aged 2-12 years with atopic dermatitis in the remission period:a multicenter,randomized,parallel-group,controlled clinical study / 中华皮肤科杂志

Objective To evaluate the effect of an emollient containing Prinsepia utilis Royle oil extracts and other extracts on clinical symptoms and disease recurrence in children aged 2-12 years with atopic dermatitis (AD) in the remission period.Methods A multicenter,randomized,parallel-group,controlled clinical trial was conducted from December 2017 to September 2018.A total of 297 children aged 2-12 years with moderate AD were enrolled from 5 hospitals in China,and randomly divided into the test group (148 cases) and control group (149 cases).In the acute stage,the two groups were both topically treated with mometasone furoate cream once a day on the skin lesions,and with an emollient containing Prinsepia utilis Royle oil extracts and other extracts twice a day throughout the whole body for 2-4 weeks.The children would be enrolled into the remission stage if their Investigator's Global Assessment (IGA) score was ≤ 1 at following visits.In the remission stage,the test group was only topically treated with the emollient twice a day throughout the whole body,while mometasone furoate cream and the emollient were both withdrawn in the control group.At weeks 4,8 and 12 in the remission stage,the recurrence of AD,eczema area and severity index (EASI),children's dermatology life quality index (CDQOL) and adverse events were evaluated.Statistical analysis was carried out with SAS 9.4 software by using t test for comparison of normally distributed continuous data between two groups,chi-square test for comparison of unordered categorical data,Kaplan-Meier method for analysis of survival rates,Cox regression analysis for evaluating the effect of different therapies on AD recurrence in children in the remission stage,and Logistic regression analysis for analysis of odds ratio (OR) of EASI or CDQOL at week 4 in the remission stage between the test group and control group.Results Of the 297 children with AD,31 breached the clinical trial protocol,and 266 were included in the per protocol set (PPS),including 132 in the test group and 134 in the control group.In the PPS,114 and 106 patients completed the follow-up in the test group and control group respectively,and the recurrence rate was significantly lower in the test group (47,41.23％) than in the control group (84,79.25％;x2 =32.96,P ＜ 0.001).The time to recurrence was significantly longer in the test group(61.99 d ± 2.80 d)than in the control group(39.17 d ± 2.54 d,t =6.03,P ＜ 0.001),and the recurrence risk was significantly lower in the test group than in the control group (Log rank test,x2 =32.02,P ＜ 0.001).After adjustment for age and gender,Cox regression analysis showed that the recurrence risk in the test group was 0.35 times that in the control group (HR =0.35,95％ CI:0.24-0.51,P ＜ 0.01).At week 4 in the remission stage,the EASI score at P50-P75 and P75-P100 in the test group were 0.42,0.25 times that in the control group respectively (95％ CI:0.20-0.86,0.12-0.54 respectively;P =0.02,＜ 0.01respectively).Moreover,the CDQOL score at P75-P100 in the test group was 0.33 times that in the control group (95％ CI:0.17-0.65,P ＜ 0.01).No significant difference in the incidence of adverse events was observed between the two groups (P ＞ 0.05).Conclusion Maintenance treatment with the emollient containing Prinsepia utilis Royle oil extracts and other extracts can markedly reduce the recurrence risk in AD children,improve clinical symptoms,and enhance the quality of life.

Changes of intrapulmonary vascular volume for chronic obstructive pulmonary disease patients based on computer-assisted measurement / 西安交通大学学报(医学版)

Objective: To investigate the changes of intrapulmonary vascular volume (IPVV) of patients with chronic obstructive lung disease (COPD) based on computer-assisted measurement. Methods: One-hundred and sixty-seven male COPD patients were collected retrospectively from the "Digital Lung" database, and divided into four subgroups: GOLD 1, GOLD 2, GOLD 3 and GOLD 4 according to the pulmonary function test of Global Initiative for Chronic Obstructive Lung Disease (GOLD). Chest CT images of 315 non-smoking normal males were collected from the "Digital Lung" database. The intrapulmonary vessels were extracted by an automated 3-dimentional protocol, IPVV of the whole lung and each lobe were obtained. The differences in IPVV between COPD and normal groups and among different COPD subgroups were compared. Results: The IPVV of the whole lung and each lobe of COPD was significantly larger than that in normal control group (P0.05). Conclusion: IPVV is a sensitive biomarker between normal cohorts and COPD patients, but cannot differentiate COPD stages.

Metformin and tanshinone llA as ethnodrugs protect heart against injury by inhibiting microRNA-1 / 中国药理学与毒理学杂志

OBJECTIVE To explore the protection mechanism of metformin and tanshinone IIA on myocardial injury. METHODS The cultured neonatal rat ventricular cells (NRVCs) were exposed to 100 μmol·L-1H2O2to simulate the in vitro model of ischemia-reperfusion injury.MTT,TUNEL and Viability/Cytotoxicity Assay were used to evaluate the effect of metformin on the viability of cardiomyocytes after treated with H2O2. The target of miR-1 was verified by Dual luciferase reporter assay. ChIP analyses was adopted to reveal the relationship between C/EBP β and miR-1.Tanshinone IIA was administrated daily for 7 d before ligation of the left anterior descending artery (LAD) and lasted for 3 months after LAD.Whole-cell patch-clamp techniques were used to measure the inward rectifying K+current(IK1)in rat isolated ventricular myocytes.GRP94,p-AMPKα,C/EBP β,CHOP,Caspase-3,Kir2.1,p38 MAPK, Cx43, MEF2 and SRF levels were analyzed by Western blot and miR-1 level was quantified by Real-time PCR.RESULTS The expression of miR-1 was significantly increased in NRVCs exposed to H2O2 in vitro. miR-1 was shown to target the 3′-untranslated region (UTR) of GRP94, which results in the accumulation of un/misfolded proteins,leading to the endoplasmic reticulum(ER)stress.C/EBP β directly induces the upregulation of miR-1 by binding to its promoter.Furthermore,metformin,a direct allosteric AMPK activator, significantly reduces C/EBP β and miR-1 levels comparing with control group. Similarly, tanshinone IIA decreased the incidence of arrhythmias and relieved ischemia-induced injury.Moreover, tanshinone IIA depressed the elevated miR-1 level and inhibited the activation of p38 MAPK and heart special transcription factors SRF and MEF2 in ischemic cardiomyocytes. CONCLUSION Metformin protects cardiomyocytes against H2O2damage through AMPK/C/EBPβ/miR-1/GRP94 pathway.Tanshi-none IIA play a role in protection cardiomyocytes from ischemic injury based on inhibiting miR-1 expres-sion through p38 MAPK signal pathway.

Changing curve of mean lung density of normal preschool children based on computer assisted measurement / 实用放射学杂志

Objective To investigate the changing curve of mean lung density (MLD)in normal preschool children based on CT quantitative measurement.Methods Chest CT data of 409 preschool children were reviewed retrospectively from the "digital lung"database.A computerized algorithm based on the "digital lung"was applied to all examinations in a batch manner.The MLD values of total lung,right lung,left lung and each lobe were obtained automatically.Results There was no correlation between the gender and MLD,however a moderately negative correlation was found between the age of month and MLD (P＜0.05).No significant difference of MLD was found between genders of the same age of month group,except in left lower lobe of 49-60 months of age (P=0.043). The MLD was decreased gradually with age (P＜0.05).Conclusion There is not a statistical difference in MLD between the preschool boys and preschool girls of the same age of month.With the growth of preschool children,the MLD is gradually decreased.

Novel Insights into the Pathogenesis of Hirschsprung's-associated Enterocolitis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To systematically summary the updated results about the pathogenesis of Hirschsprung's-associated enterocolitis (HAEC). Besides, we discussed the research key and direction based on these results.</p><p><b>DATA SOURCES</b>Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords "Hirschsprung enterocolitis", "Hirschsprung's enterocolitis", "Hirschsprung's-associated enterocolitis", "Hirschsprung-associated enterocolitis", "HAEC", and "EC".</p><p><b>STUDY SELECTION</b>Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded.</p><p><b>RESULTS</b>Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC.</p><p><b>CONCLUSIONS</b>The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung's disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system.</p>

Brain Functional Connectivity in Patients with Migraine Based on Complex Networks Analysis / 中国医学影像学杂志

Purpose To investigate the topological structure differences between the migraine patients group and the normal control group by using resting-state brain complex networks constructed based on graph theory. Materials and Methods Resting-state functional magnetic resonance imaging dataset were obtained from 22 migraine patients and 22 normal subjects. The functional complex networks of the two groups were constructed, and parameters including average clustering coefficient, characteristic path length, small worldness, assortativity, and betweenness of the two groups were respectively calculated. Results When compared with the parameters of normal control group, average clustering coefficient of migraine patients group was larger, small worldness and assortativity were also changed. The characteristic path length of the caudate nucleus and putamen areas presented abnormal in the migraine patients group. Betweenness centrality of the thalamus, inferior occipital gyrus and occipital gyrus increased in the migraine patients group. Conclusion The abnormal brain regions in the migraine patients group were mainly associated with pain processing, visual processing and sensory information relay. This study may contribute to better understanding and interpreting corresponding clinical condition of migraine.

Studies on the relationship between polymorphism of IL-28B rs8099917 and the outcome of HBV infection / 中华流行病学杂志

Objective To investigate the correlation between IL-28B rs8099917 polymorphism and the outcome of HBV infection.Methods Genotype ofrs8099917(T＞G) in IL-28B locus was determined by TaqMan SNP genotyping from 486 individuals which including 199 chronic HBV carriers (including 100 HBV-induced liver cirrhosis and 99 HBV-related HCC).143 people with selflimited infection and 144 healthy people served as controls.Multivariate analysis was used to assess the effect of IL-28B rs80999 1 7 SNP among all the studied groups.Results Distribution of genotype and allele of the rs8099917 locus were in accordance with Hardy-Weinberg equilibrium in different groups or with the total population.The frequencies of the rs8099917 TT,GT,GG genotypes were 89.3％,10.5％ and 0.2％,and the frequency of allele T and G accounted for 94.5％ and 5.5％,respectively.In respect of genotype or allele frequency,there was no significant differences found among the groups(P＞0.05 ).When comparing with the TT genotype,data from the multinomial logistic analysis showed that the ORs and (95％CI) of TG/GG genotypes were 1.589 (0.735-3.437),1.351 (0.550-3.316) and 1.704 (0.717-4.052),respectively.The genotype frequencies in different groups with different clinical features showed that TG/GG genotypes significantly increased the risk of r-GT Ⅱ( + ) for individuals with HBV-related HCC (X2=17.534,P=0.001 ),with OR as 14.821 (3.227-68.064).It was particularly so for males(X2=14.924,P=0.014),with OR(95％CI) as 45.000(2.772-730.571 ).Conclusion IL-28B rs8099917 SNP had no correlation with the outcome of HBV infection.

INFLUENCE OF CALCITONIN GENE-RELATED PEPTIDE ON THE PROLIFERATION AND PHENOTYPE TRANSFORMATION OF VASCULAR SMOOTH MUSCLE CELLS / 解剖学报

Objective To investigate whether calcitonin gene-related peptide(CGRP) can influence the proliferation and phenotypic modulation of vascular smooth muscle cells(VSMCs),and what is the relationship between them. Methods Vascular smooth muscle cells(VSMCs) were cultured respectively with rat aorta cultivated for 8 days in vitro and with normal aorta(not culture) through the explant-attached method,and CGRP was added into the culture medium of the experimental groups.The proliferation of cells was labeled by 5-bromodeoxyuridine(5-BrdU) with immunocytochemical method,and the mRNA expression of hypertension-related gene-1(HRG-1) and smooth muscle 22 alpha(SM22?) were determined by RT-PCR. Results The proliferating cells labeled by BrDU from the aorta cultured for 8 days in vitro were increased notablly and the mRNA expression of HRG-1 and SM22? were decreased.While the VSMCs were cultured in the culture medium containing CGRP,the proliferous cells labeled by BrdU were obviously decreased and the mRNA expression of HRG-1 and SM22? were significantly increased.Conclusion It is showed that CGRP could inhibit the proliferation of VSMCs and change the phenotype of VSMCs from synthesize to contractile type.It might be a good cellular model which provides a good experimental platform to research the proliferating vascular disease as well as its prevention and treatment.