SRF-rearranged cellular perivascular myoid tumor: a clinicopathological analysis of two cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor. Methods: Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed. Results: Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively. Conclusions: SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Multisensory Conflict Impairs Cortico-Muscular Network Connectivity and Postural Stability: Insights from Partial Directed Coherence Analysis / 神经科学通报·英文版

Sensory conflict impacts postural control, yet its effect on cortico-muscular interaction remains underexplored. We aimed to investigate sensory conflict's influence on the cortico-muscular network and postural stability. We used a rotating platform and virtual reality to present subjects with congruent and incongruent sensory input, recorded EEG (electroencephalogram) and EMG (electromyogram) data, and constructed a directed connectivity network. The results suggest that, compared to sensory congruence, during sensory conflict: (1) connectivity among the sensorimotor, visual, and posterior parietal cortex generally decreases, (2) cortical control over the muscles is weakened, (3) feedback from muscles to the cortex is strengthened, and (4) the range of body sway increases and its complexity decreases. These results underline the intricate effects of sensory conflict on cortico-muscular networks. During the sensory conflict, the brain adaptively decreases the integration of conflicting information. Without this integrated information, cortical control over muscles may be lessened, whereas the muscle feedback may be enhanced in compensation.

Effects of higher femoral tunnels on clinical outcomes, MRI, and second-look findings in double-bundle anterior cruciate ligament reconstruction with a minimal 5-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#To perform anatomical anterior cruciate ligament reconstruction (ACLR), tunnels should be placed relatively higher in the femoral anterior cruciate ligament (ACL) footprint based on the findings of direct and indirect femoral insertion. But the clinical results of higher femoral tunnels (HFT) in double-bundle ACLR (DB-ACLR) remain unclear. The purpose was to investigate the clinical results of HFT and lower femoral tunnels (LFT) in DB-ACLR.@*METHODS@#From September 2014 to February 2016, 83 patients who underwent DB-ACLR and met the inclusion and exclusion criteria were divided into HFT-ACLR (group 1, n = 37) and LFT-ACLR (group 2, n = 46) according to the position of femoral tunnels. Preoperatively and at the final follow-up, clinical scores were evaluated with International Knee Documentation Committee (IKDC), Tegner activity, and Lysholm score. The stability of the knee was evaluated with KT-2000, Lachman test, and pivot-shift test. Cartilage degeneration grades of the International Cartilage Repair Society (ICRS) were evaluated on magnetic resonance imaging (MRI). Graft tension, continuity, and synovialization were evaluated by second-look arthroscopy. Return-to-sports was assessed at the final follow-up.@*RESULTS@#Significantly better improvement were found for KT-2000, Lachman test, and pivot-shift test postoperatively in group 1 ( P >0.05). Posterolateral bundles (PL) showed significantly better results in second-look arthroscopy regarding graft tension, continuity, and synovialization ( P <0.05), but not in anteromedial bundles in group 1. At the final follow-up, cartilage worsening was observed in groups 1 and 2, but it did not reach a stastistically significant difference ( P >0.05). No statistically significant differences were found in IKDC subjective score, Tegner activity, and Lysholm score between the two groups. Higher return-to-sports rate was found in group 1 with 86.8% (32/37) vs. 65.2% (30/46) in group 2 ( P = 0.027).@*CONCLUSION@#The HFT-ACLR group showed better stability results, better PL, and higher return-to-sports rate compared to the LFT-ACLR group.

AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy / 中华医学杂志(英文版)

BACKGROUND@#Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.@*METHODS@#The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro . A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry.@*RESULTS@#Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro . AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 + /CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion.@*CONCLUSIONS@#This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single- Center Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. @*Materials and Methods@#We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. @*Results@#Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. @*Conclusion@#Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

The measurement of critical quality attributes of Tongren niuhuang qingxin pills based on MIF-HEMT biosensor technology / 药学学报

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the KD of which reached to 8.722×10-10 g·mL-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

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.

One-year clinical observation of the effect of internal bleaching on pulpless discolored teeth / 华西口腔医学杂志

OBJECTIVES@#This study aimed to observe the color rebound and rebound rates of non-pulp discolored teeth within 1 year after routine internal bleaching to guide clinical practice and prompt prognosis.@*METHODS@#In this work, the efficacy of bleaching was observed in 20 patients. The color of discolored teeth was measured by using a computerized colorimeter before bleaching; immediately after bleaching; and at the 1st, 3rd, 6th, 9th, and 12th months after bleaching. The L*, a*, and b* values of the color of cervical, mesial, and incisal parts of the teeth were obtained, and the color change amounts ΔE*, ΔL*, Δa*, and Δb* were calculated. The overall rebound rate (P*) and the color rebound velocity (V*) were also analyzed over time.@*RESULTS@#In 20 patients following treatment, the average ΔE* of tooth color change was 14.99. After bleaching, the neck and middle of the teeth ΔE* and ΔL* decreased in the 1st, 3rd, 6th, 9th, and 12th months, and the differences were statistically significant. Meanwhile, from the 9th month after bleaching, the rebound speed was lower than that in the 1st month, and the difference was statistically significant. The incisal end of the tooth ΔE* and ΔL* decreased in the 6th, 9th, and 12th months after bleaching, and the differences were statistically significant. No significant difference was found in the rebound speed between time points. However, this rate settled after the 9th month, with an average color rebound rate of 30.11% in 20 patients.@*CONCLUSIONS@#The results indicated that internal bleaching could cause a noticeable color change on pulpless teeth. The color rebound after bleaching was mainly caused by lightness (L*), which gradually decreased with time, and it was slightly related to a* and b*. The color of the teeth after internal bleaching rebounded to a certain extent with time, but the color rebound speed became stable from the 9th month. Clinically, secondary internal bleaching can be considered at this time according to whether the colors of the affected tooth and the adjacent tooth are coordinated and depending on the patient's needs.

ZHANG Wei-hua's clinical experience of Zhenjing Anshen method in treatment of insomnia / 中国针灸

The paper summarizes professor ZHANG Wei-hua's clinical experience in treatment of insomnia with Zhenjing Anshen (calming-down the spirit) method. It is believed that insomnia results from the unstable spirit in pathogenesis of TCM. The basic therapeutic principle is regulating the spirit, in which, stabilizing the primary spirit and tranquilizing the heart spirit are emphasized. Main acupoints are Baihui (GV 20), Sishencong (EX-HN 1) and Yintang (GV 24+) to stabilize the primary spirit, located on the head; and Shenmen (HT 7) located on the wrist to calm-down the heart spirit, as well as Sanyinjiao (SP 6) and Yongquan (KI 1) in the lower extremities to benefit yin and balance yang, and then to house the spirit eventually. The needles are inserted in different depths and to various directions. The external application of herbal plaster is combined at Yongquan (KI 1) and the supplementary acupoints are selected in terms of syndrome differentiation. This therapy is simple in acupoint selection and very effective in treatment of insomnia.

Monitoring results of plague vector fleas in Yulong ，Yunnan Province from 2019 to 2021 / 上海预防医学

ObjectiveTo analyze the community structure and dynamics of parasitic fleas on the body surface of host animals and nested fleas in different seasons in the natural foci of wild rat plague in Yulong County，Yunnan Province， to explore the relationship between seasonal fluctuation of fleas and the prevalence of plague among animals， so as to provide evidence for plague prevention and control in the natural foci. MethodsNanxi Village， Huangshan Town， the core area of plague epidemic in Yulong County， was selected as the monitoring sample area in December 2019 （winter）， August 2020（summer）， October 2020（autumn） and March 2021（spring）. Host animals were captured by rattrap at night and rat nests were excavated for collecting parasitic fleas on host animals and rat nest fleas in different seasons. Excel 2010 and SPSS 26.0 software were used to analyze the data， and Chi square test was used to compare the rate. Community ecological indicators were used to analyze the community structure and species diversity of the host animals and their parasitic fleas. ResultsA total of 355 vector fleas were captured， belonging to 7 species of 5 genera in 2 families. 441 small animals were captured and 138 rat body fleas were detected with the flea infection rate of 14.51% and the flea index 0.31. 96 effective rat holes were excavated and 217 fleas were detected with the flea infection rate of 35.42% and the flea index 2.26. Among the four seasons， the flea infection rates of rat body and rat nests were higher in summer and winter， showing a significant difference in general （χ2=15.851， P<0.01； χ2=16.398， P<0.01）. The dominant species of flea community were Ctenophthalmus quadratus， Stenischia humilis， Neopsylla specialis and Frontopsylla spadix， with a dominance index of 0.434， 0.254， 0.180 and 0.110， respectively. The diversity and evenness of rat body fleas showed a distribution characteristic of decreasing， increasing and then decreasing again with season changes， and both were the highest in spring， while the ecological dominance showed an opposite trend. The diversity and evenness of rat nest fleas showed a distribution characteristic of increasing first and then decreasing in summer， autumn and winter， with the highest in autumn， while the ecological dominance was diametrically opposite. ConclusionThe fleas community structure is relatively stable in Yulong County， but the number of species in the community is unevenly distributed by seasons， and the status of dominant species is prominent. Local authorities should carry out timely preventive deratization and depulization measures according to the results of daily monitoring， so as to effectively avoid the prevalence and spread of plague among animals in plague foci.

Influence of GLCCI1 gene rs37973 polymorphism on the efficacy of ICSs in the treatment of asthma-chronic obstructive pulmonary disease overlap / 中国药房

OBJECTIVE To investigate the association between the functional GLCCI1 gene rs37973 polymorphism and inhaled corticosteroids （ICSs） response in patients with asthma-chronic obstructive pulmonary disease overlap （ACO）. METHODS Totally 173 newly diagnosed ACO patients were recruited from Shanghai Pudong New Area People’s Hospital during April 1st， 2019 to December 31st， 2020. All patients were treated with Salmeterol fluticasone inhalation powder， twice a day， for 24 weeks. The genotype of rs37973 locus was determined， and lung function indicators [forced expiratory volume in one second （FEV1）， FEV1/forced vital capacity （FVC）， the percentage of FEV1 to expected value （FEV1%pred）]， and lung function improvement （ΔFEV1 and ΔFEV1%pred） were all detected. RESULTS Totally 111 patients completed the whole 24-week follow-up and lung function detection. Among them， there were 42 cases of AA genotype， 52 cases of AG genotype， and 17 cases of GG genotype. After 12， 24 weeks of treatment， lung function indexes of patients were significantly better than baseline lung function indexes before treatment （P＜0.05）. After 24 weeks of treatment， ACO patients with AA and AG genotypes showed significantly better lung function improvement than GG genotype， and ΔFEV1%pred of AA genotype was significantly better than AG genotype （P＜ 0.05）. After 12， 24 weeks of treatment， the improvement of lung function in patients with a smoking history ≤20 pack year was significantly better than those with a smoking history ＞20 pack year， and among patients with a smoking history ≤20 pack year， only AA genotype had significantly better FEV1%pred than AG genotype （P＜0.05）. After 12 weeks of treatment， among patients with a smoking history ＞20 pack year， the improvement of lung function in AA genotype and AG genotype was significantly better than GG genotype， and the FEV1%pred in AA genotype was significantly better than AG genotype （P＜0.05）. After 24 weeks of treatment， the improvement of lung function of AA genotype and AG genotype was significantly better than GG genotype （P＜0.05）. CONCLUSIONS GG genotype of GLCCI1 gene rs37973 locus is associated with the poor treatment response to ICSs in patients with ACO， especially in patients with smoking history ＞20 pack year.

Correlations of β-catenin expression with clinical efficacy of tyrosine kinase inhibitors and prognosis of advanced lung adenocarcinoma patients with epidermal growth factor receptor mutations / 肿瘤研究与临床

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Multimodal imaging features of perifoveal exudative vascular anomalous complex / 中华眼底病杂志

Objective:To observe the multimodal imaging features and explore the treatment of parafoveal exudative vascular anomaly complex (PEVAC).Methods:A retrospective study. Six patients (6 eyes) with PEVAC diagnosed in Tianjin Eye Hospital were included in this study from July 2018 to December 2021. All patients were female with monocular disease. The age was (61.1±9.3) years. All patients showed a sudden painless decline in monocular vision with metamorphopsia. All patients underwent best corrected visual acuity (BCVA), color fundus photography, fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and OCT angiography (OCTA). Indocyanine green angiography (ICGA) was performed in 4 eyes. In 6 eyes, 3 eyes were treated with intravitreal injection of anti-vascular endothelial growth factor drug; 5 eyes were treated with micropulse laser photocoagulation and/or local thermal laser photocoagulation; 1 eye was treated with photodynamic therapy. Five patients were followed up for (9.2±7.4) months, and 1 patient was lost. At follow-up, the same equipment and methods were used as at the initial diagnosis. The clinical manifestations, multimodal image features and treatment response were observed.Results:Baseline BCVA of affected eyes were ranged from 0.1 to 0.5. PEVAC was isolated in 6 eyes, and the fundus showed isolated hemangioma-like leision, accompanied by small bleeding and hard exudation. There were 2 isolated hemangiomatous lesions adjacent to each other in 2 eyes. In the early stage of FFA, punctate high fluorescence lesions near the macular fovea were seen, and the leakage was enhanced in the late stage. There was no leakage in the early stage of ICGA, or slight leakage with late scouring. OCT showed an oval lesion with high reflection wall and uneven low reflection. The central macular thickness (CMT) was (431±76) μm. OCTA showed blood flow signals in PEVAC, 2 eyes in the superficial capillary plexus (SCP), and it was also observed in the deep capillary plexus (DCP), but the intensity of blood flow signal was slightly weaker than that in the SCP. The blood flow signal was visible only in DCP in 2 eyes. SCP and DCP showed similar intensity of blood flow signals in 2 eyes. After treatment, the bleeding was absorbed basically in 4 eyes, the hard exudation partially subsided, the CMT decreased, the intercortical cystic cavity of the fovea nerve decreased, the hemangiomatous lesions narrowed, and BCVA increased. In 1 eye, the macular sac was reduced and partially absorbed by hard exudation, which was later relapsed due to blood pressure fluctuation.Conclusions:The majority of PEVAC patients had monocular onset. The fundus is characterized by solitary or structure with strong reflex walls, with or without retinal cysts, hard exudates, and subretinal fluid, and visible blood flow signals inside.

Interpretation of presynaptic dopaminergic PET imaging results / 中华核医学与分子影像杂志

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

Study on the characteristics of 18F-flurodeoxyglucose uptake in the microenvironment of hepatic alveolar echinococcosis / 中华肝胆外科杂志

Objective:To investigate characteristics of the 18F-flurodeoxyglucose ( 18F-FDG) uptake intensity and ranges in distinct hepatic alveolar echinococcosis lesions. Methods:The clinical data of 39 patients with position emission tomography during Jan 2017 to Dec 2019 in the First Affiliated Hospital of Xinjiang Medical University were enrolled. Among them, there were 17 males and 22 females, aging from 15 to 65 years (median 34 years). Lesions were classified into six groups based on heterogenic scales of calcification and liquefaction: A. non-calcified and non-liquefied ( n=7); B. obvious calcified and non-liquefied ( n=7); C. partial calcified and partial liquefied( n=10); D. obvious calcified and partial liquefied ( n=5); E. partial calcified and subtotal liquefied ( n=5); F. obvious calcified and subtotal liquefied ( n=5). Tumor to background ratio (TBR) and width (W) of lesion infiltrative boundary were measured and calculated. Statistical comparison using Mann-Whitney U test as well as correlation analysis was performed. Results:TBR values [ M( Q1, Q3)] for each group were 4.40(3.66, 7.03), 2.55(1.69, 3.60), 3.73(3.37, 5.21), 2.90(2.75, 3.60), 3.80(3.49, 6.36), 2.49(2.21, 3.97), among which A>B, A>D, A>F, C>B, E>B ( U=3.0, 4.0, 4.5, 11.0, 5.0, all P<0.05); From the perspective of the calcification in each group, it was found that the lighter the calcification was, the greater the TBR value was. W values [ M( Q1, Q3)] for each group were [12.5(10.0, 19.5), 11.2(10.5, 12.5), 12.2(10.9, 13.2), 7.8(7.3, 9.3), 10.0(7.3, 13.4), 7.3(6.8, 7.6)] mm, among which A>D, A>F, B>D, B>F, C>D, C>F (all U=0, all P<0.05); According to the degree of calcification and liquefaction of lesions in each group, the lighter the calcification was, the greater the W value was; The heavier the liquefaction was, the smaller the W value was. A mild strength linear correlation has been observed between the TBR value and W value ( r=0.4136, P<0.05). Conclusions:Less calcification and liquefaction implicated higher 18F-FDG uptake intensity and wider range. Radical resection margins and tissue sampling should be individualized based on different lesion features in surgical treatment.

Clinical study of the relationship between cellular adhesion molecules and left ventricular geometry and function in patients with obstructive sleep apnea syndrome and prehypertension / 中华超声影像学杂志

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.