[Observation on the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation for the treatment of tremor-dominant subtypes of Parkinson's disease].

Objective: To analyze the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation (rTMS) for the treatment of tremor Parkinson's disease(PD). Method: A total of 82 patients with primary PD who were admitted to the Department of Neurology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 1, 2020 to March 31, 2021 were prospectively collected. According to the clinical characteristics of major movement disorders, 82 patients with tremor type (TD) were selected to enroll.The patients were randomly divided into 3 groups at a 1∶1∶1 ratio according to the randomized coding sequence of the trial: the primary motor cortex (M1) group with 26 cases, the cerebellum group with 26 cases and the dual-site (M1, cerebellum) group with 30 cases. All patients were treated with 1 Hz low-frequency stimulation of the corresponding target once a day for 5 days a week for 2 weeks, a total of 10 times; The dosage remained unchanged during the treatment for all groups. Before and after 2 weeks' treatment, the patients were assessed with the Unified PD Rating Scale (UPDRS) and PD Quality of Life Questionnaire-39 (PDQ-39) without medication. Cortical excitability, namely transcranial magnetic stimulation motor evoked potential (TMS-MEP), [including resting motor threshold (rMT) and active motor threshold (aMT) examinations], timed up and go (TUG) and electromyographic tremor were conducted. Result: There were 82 patients, 39 males and 43 females, with an average age of (67±8) years. Before the treatment, there was no statistically significant difference in the evaluation indicators among the three groups (all P>0.05). After the treatment, the differences of the UPDRS-Ⅲ score [(38.9±2.5) vs (29.2±3.6) ], UPDRS tremor score [(23.7±2.1) vs (14.6±3.1) ], TUG time [(44.8±3.1) s vs (33.7±4.1) s], tremor amplitude [(480±126) µV vs (276±94) µV], PDQ-39 score [(51±13) vs (45±13) ], rMT [(36±17)% vs (43±13)%], and aMT [(26±16)% vs (31±12)%] were statistically significant (all P<0.01) from those before the treatment. There was no statistical difference in the above factors between the M1 group and cerebellum group (all P>0.05). There was no statistically significant difference in tremor peak frequency among the three groups before and after the treatment (all P>0.05). Conclusions: Dual-site low-frequency rTMS can improve PD tremor, while M1 or cerebellar low-frequency rTMS does not significantly improve PD tremor. Its mechanism may be to improve PD tremor symptoms by regulating cortical excitability.

Measurement of oesophageal hiatus surface area by multiplanar reconstruction of MDCT: relationship with lower oesophageal sphincter pressure and acid reflux.

AIM: To evaluate the relationship between oesophageal hiatus surface area (OHSA) and gastro-oesophageal reflux disease (GERD). MATERIALS AND METHODS: Patients who underwent 24-h pH monitoring, oesophageal high-resolution manometry, and upper abdominal contrast-enhanced multidetector computed tomography (MDCT) during 2014-2021 were enrolled. Patients with a hiatus hernia (HH) on MDCT or who had a history of gastro-oesophageal surgery were excluded. Multiplanar reconstruction (MPR) of the MDCT image was used for the measurement of OHSA. Correlations of OHSA with acid exposure time (AET) and lower oesophageal sphincter (LOS) pressure of all patients were analysed. RESULTS: Seventy-eight patients were included in the study. OHSA was much less in the AET <4% group than in the AET >6% group (1.61 ± 0.42 versus 2.09 ± 0.55 cm2, p<0.001). Correlation analysis reveals that OHSA correlated positively with AET (correlation coefficient = 0.47, p<0.001). Receiver operating characteristic (ROC) curve analysis reveals that OHSA can significantly distinguish patients in different groups divided by AET (area under the ROC curve [AUC] = 0.76, 95% confidence interval [CI]: 0.63-0.90). OHSA was not related to LOS pressure (correlation coefficient = -0.268, p=0.051). There was no difference in OHSA between the low LOS pressure group and the normal LOS pressure group (1.84 ± 0.61 versus 1.74 ± 0.50 cm2, p=0.52). CONCLUSIONS: OHSA significantly correlated with AET but has no relationship with LOS pressure. It may be an independent risk factor of GERD.

[Establishment of a novel co-cultured liver cancer model based on tumor microenvironment].

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 µg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.

Observation of a Strongly Isospin-Mixed Doublet in

ß decay of proton-rich nuclei plays an important role in exploring isospin mixing. The ß decay of ^{26}P at the proton drip line is studied using double-sided silicon strip detectors operating in conjunction with high-purity germanium detectors. The T=2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in ^{26}Si are unambiguously identified through ß-delayed two-proton emission (ß2p). Angular correlations of two protons emitted from ^{26}Si excited states populated by ^{26}P ß decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the ^{26}Si IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in ß-decay experiments.

[The clinical efficacy of the stratification medical treatment based on the risk estimation of motor complications in Parkinson's disease].

Objectives: To evaluate the clinical efficacy of the stratification medical treatment based on the motor complications risk estimation in improving the quality of life, motor symptoms and delaying the motor complications in Parkinson's patients. Methods: Outpatients and inpatients from Xinhua Hospital, Shanghai Jiao Tong University, were recruited between November 2019 and June 2020. The participants were all clinically diagnosed with PD and treated with anti-PD medications, but had no history of motor complications, with the 8-item Parkinson's disease questionnaire summary index (PDQ-8 SI)>18.59. At baseline, the demographic characteristics, PD medical history, levodopa dosage (LD) and levodopa equivalent dosage (LED) were collected, and the evaluation of PDQ-8, Unified Parkinson's disease rating scale (UPDRS)-Ⅱ and Ⅲ, Hoehn and Yahr (H&Y) grade, Hamilton anxiety scale-14 (HAMA-14), Hamilton depression scale-24 (HAMD-24), mini-mental state examination (MMSE), Pittsburgh sleep quality index (PSQI), and Epworth sleepiness scale (ESS) tools was accomplished in all participants. Meanwhile, a Parkinson's disease risk estimation scale for motor complications was used to assess patients' risk of motor complications, and thus the medication was stratified in PD patients accordingly. During the 6-month and 12-month follow-ups, the evaluation of the above-mentioned parameters was repeated in all participants. At the 3-month and 9-month follow-ups, the information of anti-PD medications, the occurrence of motor complications (motor fluctuations and dyskinesia) and adverse drug reactions were recorded, and PDQ-8 was also evaluated. Results: Two hundred and fifty-one patients completed the 1-year follow-up, with 135 males and 116 females. At baseline, the median age of the patients was 66 (60, 71) years and the median PDQ-8 SI was 31.2 (21.9, 40.6). Additionally, 15.9% (40/251) of the patients were at high risk of motor fluctuation, and 7.2% (18/251) were at high risk of dyskinesia. There were significant differences in the age of onset, disease duration, PD treatment duration, the scores of UPDRS-Ⅱ and Ⅲ, H&Y Grade, and PDQ-8 SI among PD patients of different risk groups (all P<0.05). In the 12th month, the median of PDQ-8 SI, Δ PDQ-8 SI and Δ UPDRS-Ⅲ was 12.5 (9.4, 18.8), -15.6 (-21.9, -9.4) and -9(-16, -4), respectively, which was statistically different from that of baseline (all P<0.05). The change of UPDRS-Ⅱ scores in the group with high risk of motor fluctuation was statistically different from that in the groups with low and moderate risk (P<0.05). The changes of PSQI score, LD and LED in the group with high risk of dyskinesia was statistically different from those in the groups with low and moderate risk (all P<0.05). During the follow-up, the incidence of motor fluctuation and dyskinesia was 9.56% (24/251) and 5.97% (15/251), respectively. Conclusion: The stratification medical treatment might have a positive intervention effect on promoting a better quality of life, improving motor symptoms and delaying motor complications in PD patients.

16S rRNA gene amplicon sequencing of gut microbiota in gestational diabetes mellitus and their correlation with disease risk factors.

PURPOSE: Although the gut microbiota (GM) are associated with various diseases, their role in gestational diabetes mellitus (GDM) remains uncharacterized. Further study is urgently needed to expose the real relationship between GM and GDM. METHODS: We performed a prospective study in 33 pregnant Chinese individuals [15, GDM; 18, normal glucose tolerance (NGT)] to observe the fecal microbiota by 16S rRNA gene amplicon sequencing at 24-28 weeks of gestational age after a standard 75 g oral glucose tolerance test. Linear regression analysis was employed to assess the relationships between the GM and GDM clinical parameters. RESULTS: Sequencing showed no difference in the microbiota alpha diversity but a significant difference in the beta diversity between the GDM and NGT groups, with the relative abundances of Ruminococcus bromii, Clostridium colinum, and Streptococcus infantis being higher in the GDM group (P < 0.05). The quantitative PCR results validated the putative bacterial markers of R. bromii and S. infantis. Moreover, a strong positive correlation was found between S. infantis and blood glucose levels after adjusting for body mass index (P < 0.05). CONCLUSION: Three abnormally expressed intestinal bacteria (R. bromii, C. colinum, and S. infantis) were identified in GDM patients. S. infantis may confer an increased risk of GDM. Hence, the GM may serve as a potential therapeutic target for GDM.

Preliminary study on alleviation of heat-induced intestinal inflammation through compensatory effects of glucose oxidase.

1. The influence of glucose oxidase (GOD) supplementation on growth, gut inflammation and its compensatory effects in broilers was investigated before and after heat stress.2. Before heat stress, one-day-old broilers were divided into two groups: the control (CON) and GOD (100 g/t complete feed) groups. On d 21, the CON group was equally divided into CON1 and CON2 groups, and heat stress (35°C) was applied to the CON2 and GOD groups for 8 h/day to the end of the study, d 27 of age. The chickens were either killed before heat stress and 2 d after heat stress for the determination of cytokines in the liver and ileum, serum antioxidant enzymes and ileal microbiota. Growth performance was determined before and 7 d after heat stress.3. The GOD decreased Clostridiales and Enterobacteriaceae families of bacteria and increased ileal nuclear factor-κB, interleukin-1ß, and interferon-γ (P < 0.05) before heat stress. The broilers exhibited compensatory effects, including increases in ileal sirtuin-1, heat shock protein 70 expression, liver nuclear factor erythroid 2-related factor 2 content, serum total antioxidant capacity and glutathione peroxidase level (P < 0.05). At 2 d after heat stress, inflammatory factors were increased in both the CON2 and GOD groups, but the levels were lower in the GOD than CON2 (P < 0.05). On d 7 after heat stress, GOS alleviated heat stress induced growth retardation (P < 0.05).4. These data suggested that GOD supplementation in broiler diets before heat stress stimulated intestinal oxidative stress and produced a compensatory response, which prevented a rapid increase in intestinal inflammatory factors and helped to maintain growth performance under heat stress.

MiR-495-3p and miR-143-3p co-target CDK1 to inhibit the development of cervical cancer

Purpose The GEO database and KEGG database-based analyses identified the differential expression of cyclin-dependent kinase 1 (CDK1) in cervical cancer and its involvement in the cell cycle pathway. In the present study, we aim to clarify the role of CDK1 in cervical cancer and the function of upstream microRNA (miR)-143-3p/miR-495-3p. Methods The expression of miR-143-3p, miR-495-3p, and CDK1 in cervical cancer tissues and cells was determined using RT-qPCR. Cell bioactivities were examined by CCK-8 and flow cytometry. The binding affinity between CDK1 and miR-143-3p/miR-495-3p was investigated using dual luciferase gene reporter assay. A xenograft mouse model of cervical cancer was then established to explore their effect on the tumorigenicity of cervical cancer cells in vivo. Results CDK1 was found to be the common target gene of miR-143-3p and miR-495-3p. CDK1 overexpression occurred in cervical cancer tissues and cells, while expression of miR-495-3p and miR-143-3p was down-regulated. The viability was inhibited while the apoptosis was promoted in cervical cancer cells in response to miR-143-3p or miR-495-3p overexpression, or CDK1 silencing. Further, miR-143-3p or miR-495-3p overexpression was also substantiated to inhibit the tumorigenicity of cervical cancer cells in vivo, while CDK1 overexpression counteracted their effect. Conclusion Taken together, miR-143-3p and miR-495-3p co-target CDK1, thereby inhibiting the occurrence and development of cervical cancer (AU)

[Extraskeletal mesenchymal chondrosarcoma in central nerve system: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2. Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.

MiR-495-3p and miR-143-3p co-target CDK1 to inhibit the development of cervical cancer.

PURPOSE: The GEO database and KEGG database-based analyses identified the differential expression of cyclin-dependent kinase 1 (CDK1) in cervical cancer and its involvement in the cell cycle pathway. In the present study, we aim to clarify the role of CDK1 in cervical cancer and the function of upstream microRNA (miR)-143-3p/miR-495-3p. METHODS: The expression of miR-143-3p, miR-495-3p, and CDK1 in cervical cancer tissues and cells was determined using RT-qPCR. Cell bioactivities were examined by CCK-8 and flow cytometry. The binding affinity between CDK1 and miR-143-3p/miR-495-3p was investigated using dual luciferase gene reporter assay. A xenograft mouse model of cervical cancer was then established to explore their effect on the tumorigenicity of cervical cancer cells in vivo. RESULTS: CDK1 was found to be the common target gene of miR-143-3p and miR-495-3p. CDK1 overexpression occurred in cervical cancer tissues and cells, while expression of miR-495-3p and miR-143-3p was down-regulated. The viability was inhibited while the apoptosis was promoted in cervical cancer cells in response to miR-143-3p or miR-495-3p overexpression, or CDK1 silencing. Further, miR-143-3p or miR-495-3p overexpression was also substantiated to inhibit the tumorigenicity of cervical cancer cells in vivo, while CDK1 overexpression counteracted their effect. CONCLUSION: Taken together, miR-143-3p and miR-495-3p co-target CDK1, thereby inhibiting the occurrence and development of cervical cancer.

[Investigation on high-frequency hearing loss of noise workers in an automobile factory].

Objective: To investigate the high-frequency hearing loss (HFHL) of workers in an automobile factory and its influencing factors, so as to provide a scientific basis for occupational health management of noise workers. Methods: From March to July 2019, 2647 workers from an automobile factory were selected as the research objects by cluster sampling method. The basic personal information (such as gender, age, education level, height, weight, etc.) , history of ear disease, the history of detonation, history of exposure to ototoxic drugs, history of exposure to occupational noise, etc., were investigated by questionnaire and occupational health examination. Chi-square test was used to compare the detection rates of HFHL in different populations, and multivariate logistic regression model was used to analyze the influencing factors of HFHL. Results: The noise level of 2647 individual workers ranged from 75.0 dB (A) to 92.0 dB (A) , with an average of (84.14±2.47) dB (A) . The detection rate of HFHL was 17.2% (456/2647) . There were significant differences in the the detection rate of HFHL among workers of different gender, age, educational level, working age, noise exposure level, diabetes history, detonation history, smoking and drinking workers (P<0.05) . Multivariate logistic regression analysis showed that male, age ≥30 years old, smoking and noise exposure were risk factors for HFHL (P<0.05) . Conclusion: The detection rate of HFHL in automobile factory workers is high. Gender, age, smoking and noise are the influencing factors of HFHL. It is necessary to strengthen the noise control in the workplace and guide workers to choose healthy lifestyle.

New α-Emitting Isotope

A new α-emitting isotope ^{214}U, produced by the fusion-evaporation reaction ^{182}W(^{36}Ar,4n)^{214}U, was identified by employing the gas-filled recoil separator SHANS and the recoil-α correlation technique. More precise α-decay properties of even-even nuclei ^{216,218}U were also measured in the reactions of ^{40}Ar, ^{40}Ca beams with ^{180,182,184}W targets. By combining the experimental data, improved α-decay reduced widths δ^{2} for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N=126 are deduced. Their systematic trends are discussed in terms of the N_{p}N_{n} scheme in order to study the influence of proton-neutron interaction on α decay in this region of nuclei. It is strikingly found that the reduced widths of ^{214,216}U are significantly enhanced by a factor of two as compared with the N_{p}N_{n} systematics for the 84≤Z≤90 and N<126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the π1f_{7/2} and ν1f_{5/2} spin-orbit partner orbits, which is supported by the large-scale shell model calculation.

New

The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.

A multi-institutional study of patient-derived gender-based discrimination experienced by resident physicians.

BACKGROUND: This study characterizes prevalence, frequency, and forms of patient-derived gender-based discrimination (GBD) experienced by resident physicians, as well as their experiences witnessing and reporting patient-derived GBD. METHODS: A web-based survey was sent to residents from 12 programs at three academic institutions. RESULTS: Response rate was 47.9% (309/645) with 55.0% of respondents identifying as women. Women were more likely than men to experience patient-derived GBD during residency (100% vs 68.8%, p < 0.001), including inappropriate physical contact, receiving less trust from patients, and being mistaken for a nurse (p < 0.001). While 85.9% of residents personally experienced and 95.0% of residents witnessed patient-derived GBD, only 3.4% of residents formally reported patient-derived GBD. Women were more likely to report negative personal and professional consequences of patient-derived GBD. CONCLUSIONS: Patient-derived GBD is pervasive and disproportionately affects women residents. Current reporting mechanisms are not adequately capturing nor addressing patient-derived GBD.

[Current status and research progress of third-line treatment for patients with gastric cancer in China].

Gastric cancer (GC) is one of the most common malignant tumors in the world. The prognosis of advanced GC is extremely poor, characterized by the high recurrence or disease progression rate after the first-line chemotherapy, and the extremely low long-term survival rate. Meanwhile, the options for subsequent treatment are limited. Studies have shown that the third-line therapy can provide significant survival benefits for selected patients with advanced GC. Currently, a series of randomized controlled trials and real-world studies related to chemotherapy, targeted therapy, and immunotherapy are conducted. In addition, the explorations of combination therapy, and screening the optimal clinical features or predictive biomarkers for the suitable population who might benefit from the third-line regimens are the hot spots for researchers. This article will provide a detailed overview of the current status and progress of the third-line treatment for advanced GC, and to illustrate the characteristics of Chinese GC treatment.

A Prospective Study of Diffusion-weighted Magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus.

AIMS: The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a prognostic marker of treatment response would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent diffusion coefficient (ΔADCmean) between a DW-MRI at diagnosis and on fraction 8-10 of chemoradiotherapy (CRT) as a biomarker for cellularity, and correlate these with anal squamous cell carcinoma recurrence. MATERIALS AND METHODS: This prospective study recruited patients with localised anal cancer between October 2014 and November 2017. DW-MRI was carried out at diagnosis and after fraction 8-10 of radical CRT. A region of interest was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T2-weighted images and propagated to the ADC map. Routine clinical follow-up was collected from Nation Health Service electronic systems. RESULTS: Twenty-three of 29 recruited patients underwent paired DW-MRI scans. Twenty-six regions of interest were delineated among the 23 evaluable patients. The median (range) tumour volume was 13.6 cm3 (2.8-84.9 cm3). Ten of 23 patients had lesions with ΔADCmean ≤ 20%. With a median follow-up of 41.2 months, four patients either failed to have a complete response to CRT or subsequently relapsed. Three of four patients with disease relapse had lesions demonstrating ΔADCmean <20%, the other patient with persistent disease had ΔADCmean of 20.3%. CONCLUSIONS: We demonstrated a potential correlation between patients with ΔADCmean <20% and disease relapse. Further investigation of the prognostic merit of DW-MRI change is needed in larger, prospective cohorts.

Determinants of SARS-CoV-2 receptor gene expression in upper and lower airways.

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.