Development of a novel combined nomogram integrating deep-learning-assisted CT texture and clinical-radiological features to predict the invasiveness of clinical stage IA part-solid lung adenocarcinoma: a multicentre study.

AIM: To develop a novel combined nomogram based on deep-learning-assisted computed tomography (CT) texture (DL-TA) and clinical-radiological features for the preoperative prediction of invasiveness in patients with clinical stage IA lung adenocarcinoma manifesting as part-solid nodules (PSNs). MATERIALS AND METHODS: This study was conducted from January 2015 to October 2021 at three centres: 355 patients with 355 PSN lung adenocarcinomas who underwent surgical resection were included and classified into the training (n=222) and validation (n=133) cohorts. PSN segmentation on CT images was performed automatically with a commercial deep-learning algorithm, and CT texture features were extracted. The least absolute shrinkage and selection operator was used for feature selection and transformed into a DL-TA score. The combined nomogram that incorporated the DL-TA score and identified clinical-radiological features was developed for the prediction of pathological invasiveness of the PSNs and validated in terms of discrimination and calibration. RESULTS: The present study generated a combined nomogram for predicting the invasiveness of PSNs that included age, consolidation-to-tumour ratio, smoking status, and DL-TA score, with a C-index of 0.851 (95% confidence interval: 0.826-0.877) for the training cohort and 0.854 (95% confidence interval: 0.817-0.891) for the validation cohort, indicating good discrimination. Furthermore, the model had a Brier score of 0.153 for the training cohort and 0.135 for the validation cohort, indicating good calibration. CONCLUSION: The developed combined nomogram consisting of the DL-TA score and clinical-radiological features and has the potential to predict the individual risk for the invasiveness of stage IA PSN lung adenocarcinomas.

Anaemia prevalence and risk factors among children aged 6 to 23 months in rural China.

INTRODUCTION: Anaemia is a global public health problem among children. However, few studies have examined anaemia prevalence and risk factors among Chinese children of different ages, particularly in poor rural areas. This study investigated these two aspects among children aged 6 to 23 months in poor rural areas of China. METHODS: This cross-sectional study included 1132 children aged 6 to 23 months in three prefectures of the Qinba Mountains area. A finger prick blood test for haemoglobin and anaemia was conducted, along with household surveys of socio-demographic characteristics, illness characteristics, and feeding practices. Multiple linear and logistic regression analyses were used to determine predictors of anaemia. RESULTS: Overall, 42.6% of children in the study displayed anaemia. Children aged 6 to 11 months had the highest anaemia prevalence (53.6%). Anaemia risk factors differed among age-groups and throughout the overall sample. Bivariate and multivariable regression results showed that continued breastfeeding, any history of formula feeding, and consumption of iron-rich or iron-fortified foods were prominent risk factors for anaemia. However, continued breastfeeding and any history of formula feeding had the greatest impact across age-groups (both P<0.05). CONCLUSION: Anaemia remains a severe public health problem among children aged 6 to 23 months in rural China. Healthy feeding practices, nutritional health knowledge, and nutrition improvement projects are needed to reduce the burden of anaemia among children in rural areas of China.

METTL21C mediates lysine trimethylation of IGF2BP1 to regulate chicken myoblast proliferation.

1. Methyltransferase-like 21C (METTL21C) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) play important roles in the proliferation of chicken myoblasts. However, it remains unclear whether there is protein-protein interaction between METTL21C and IGF2BP1 to regulate proliferation of chicken myoblasts.2. In this study, the Igf2bp1 gene was amplified from cDNA of liver tissue of Lueyang black-bone chicken to construct the overexpression vector HA-Igf2bp1. The HA-Igf2bp1 and Flag-Mettl21c vectors were individually transfected and co-transfected into HEK293T, respectively. Co-immunoprecipitation (Co-IP) assay indicated a protein-protein interaction between METTL21C and IGF2BP1.3. Using the Western blotting and LC-MS/MS, it was found that METTL21C could mediate the lysine methylation modification of IGF2BP1. Furthermore, the His-tagged overexpression vector HA-Igf2bp1-His was constructed, transfected and co-transfected with Flag-Mettl21c into HEK293T. His-tagged IGF2BP1 was purified by nickel ion affinity chromatography. Western blotting revealed that IGF2BP1 was successfully purified, and the trimethylation modification level of co-transfection group was significantly elevated compared with the single-transfection Igf2bp1 group.4. Mettl21c and Igf2bp1 overexpression vectors were transfected and co-transfected into primary chicken myoblasts, respectively. The results of 5-ethynyl-2'-deoxyuridine assay and the expression level of Pax7 and MyoD indicated that overexpression of Igf2bp1 alone inhibited the chicken myoblast proliferation, whereas co-expression of Mettl21c and Igf2bp1 eliminated the inhibitory effects of Igf2bp1, thereby favouring cell proliferation and differentiation.5. The results, for the first time, revealed that METTL21C mediated the lysine trimethylation modification of IGF2BP1 to regulate the proliferation of chicken myoblasts, which provided a new insight into in-depth analysis of the molecular mechanism of METTL21C methylation involved in regulating the growth and development of skeletal muscle in Lueyang black-bone chicken.

[Correction model of the sampling time error on the blood trough concentration of tacrolimus in non-sustained-release dosage form for renal transplant recipients].

Objective: To establish correction model of the sampling time error on the blood trough concentration of tacrolimus in non-sustained-release dosage form for renal transplant recipient and improve the accuracy of drug dose assessment and clinical adjustment in renal transplant recipients. Methods: Visit records of 206 outpatients in the Department of Transplantation, Nanfang Hospital, Southern Medical University were retrospectively collected from October 15, 2022 to October 30, 2022. The distribution of sampling time of tacrolimus blood drug concentration was described and the time range of correction was determined. Twenty inpatients after renal transplantation in the Department of Transplantation, Nanfang Hospital, Southern Medical University from October 1, 2022 to November 30, 2022 were prospectively included, and their demography data, laboratory test results during follow-ups, and CYP3A5 genotype were collected. The patients took tacrolimus in non-sustained-release dosage form every 12 h starting from 19∶30 on the day of admission. Peripheral blood samples were collected from the patients on the second day of admission at 7∶30 and on the third day at 6∶00-10∶00 every 30 minutes to test the blood concentration of tacrolimus. Using the collection time as the independent variable and the blood tacrolimus concentration as the dependent variable, a simple linear regression was performed to fitting a linear model of tacrolimus blood concentration-sampling time. Multiple linear regression was performed to analyze the influencing factors of the tacrolimus metabolic rate within a specific period and generate the regression equation. Results: The 206 outpatients aged (46±13) years, including 131 males (63.6%). The time gap [M (Q1, Q3)] between the sampling time of the follow-up outpatients and standard C12 was 24 (13.0, 46.5) min, and the maximum time gap was 135 min. The 20 enrolled inpatients aged (45±12) years, including 15 males (75.0%). There was no significant difference in the blood concentration of tacrolimus collected at 7∶30 on the second (7.87±2.21)ng/ml and third days (7.84±2.33)ng/ml after admission of the enrolled inpatients (P=0.917), and the blood tacrolimus concentration rhythm was stable in the trial. The plasma concentration of C10.5-C14.5 was linearly related to the time, with R2 [M (Q1, Q3)] 0.88 (0.85, 0.92) and all P<0.05. The metabolic rate of tacrolimus during C10.5-C14.5=0.984+0.090×basic concentration of tacrolimus (ng/ml)-0.036×body mass index+0.489×CYP3A5 genotype-0.007×hemolobin(g/L)-0.035×alanine aminotransferase (U/L)+0.143×total cholesterol (mmol/L)+0.027×total bilirubin (µmol/L), with R2=0.85. Conclusion: This study propose a correction model for tacrolimus (non-sustained-release dosage form) trough concentration around C12, which is helpful for clinicians to easily and accurately assess renal transplant recipients' tacrolimus exposure.

[Efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis].

Objective: To explore the efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis. Methods: A cohort study. The clinical data of patients with refractory chronic gouty arthritis who were treated with rasburicase at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between January 2021 and July 2022 were retrospectively analyzed. Refractory chronic gouty arthritis was defined as serum uric acid (sUA)>360 µmol/L and urate volume>10 cm3 under dual-energy computed tomography after tolerable maximal oral urate-lowering therapy for at least 3 months. The administration of low-dose rasburicase was applied intravenously with total dosage ranging from 4.5 to 7.5 mg each dose, at 4-week intervals for a maximum of three doses. Efficacy was evaluated by the changes of sUA level, tophus and urate volume. Results: A total of 22 patients were included for analysis, with 95.4% (21/22) male, the mean age was (44±15) years, and the median duration of gout was 11 (6-15) years. The mean sUA at baseline was (667±112) µmol/L. The levels of sUA significantly decreased after each dose of rasburicase (P<0.001), and the median reduction of sUA after each dose of rasburicase was 568 (471-635), 187 (66-335) and 123 (49-207) µmol/L, respectively. At week 12, nine patients (40.9%) exhibited sUA<360 µmol/L and tophus disappeared in one patient. The urate volume significantly decreased at week 12 when compared with that before the first dose of rasburicase in all the patients [40 (16-172) cm3 vs 17 (7-134) cm3, P<0.001], with a median reduction rate of 41.6% (22.9%-58.5%). The everall safety of rasburicase was good, and no serious adverse reactions occurred. Conclusions: Low-dose rasburicase is well-tolerated and effective for decreasing the urate burden in patients with refractory chronic gouty arthritis. Further prospective randomized controlled trials are needed to validate these findings.

[Construction of a dual fluorescent reporter system for tracing horizontal transfer of mcr-1-carrying plasmid].

The green fluorescent reporter gene was inserted into the gene interval of polymyxin resistant mcr-1-carrying plasmid (pSH13G841) by homologous recombination of suicide plasmid. At the same time, E. coli J53 with red fluorescent reporter gene was constructed. Using the ability of spontaneous conjugation of drug resistant plasmid (pSH13G841), pSH13G841-GFP plasmid was transferred into J53 RFP bacteria to construct a double fluorescent labeled donor bacterium. The two light-emitting systems could stably and spontaneously express fluorescence without mutual interference. The dual fluorescence report system constructed can be used for visual tracing horizontal transfer of mcr-1-carrying plasmid, the subsequent model can study the colonization, transfer and prognosis of drug-resistant bacteria/drug-resistant genes mcr-1 by using mouse in vivo imaging technology.

[Advances in clinical characteristics of talaromycosis combined with other opportunistic infections].

Talaromycosis (TSM) is an opportunistic deep mycosis prevalent in southeast Asia and southern China, affecting HIV-positive, anti-interferon-gamma autoantibody-positive and other immunodeficiency hosts. These hosts are often co-infected with mycobacterium tuberculosis, non-tuberculosis mycobacteria, bacteria, fungi, viruses and other opportunistic infections. The clinical characteristics and the pathogenic spectrum of TSM with opportunistic infections vary with different immune states. The rates of misdiagnosis, missed diagnosis and mortality are high. This review summarized the clinical characteristics of TSM with opportunistic infections in order to improve the level of clinical diagnosis and treatment.

CT texture analysis-based nomogram for the preoperative prediction of visceral pleural invasion in cT1N0M0 lung adenocarcinoma: an external validation cohort study.

AIM: To develop a nomogram based on computed tomography (CT) texture analysis for the preoperative prediction of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma. MATERIALS AND METHODS: A dataset of chest CT containing lung nodules was collected from two institutions, and all surgically resected nodules were classified pathologically based on the presence of visceral pleural invasion. Each nodule on the CT image was segmented automatically by artificial-intelligence software and its CT texture features were extracted. The dataset was divided into training and external validation cohorts according to the institution, and a nomogram for predicting visceral pleural invasion was developed and validated. RESULTS: Of a total of 313 patients enrolled from two independent institutions, 63 were diagnosed with visceral pleural invasion. Three-dimensional (3D) CT long diameter, skewness, and sphericity, and chronic obstructive pulmonary disease were identified as independent predictors for visceral pleural invasion by multivariable logistic regression. The nomogram based on multivariable logistic regression showed great discriminative ability, as indicated by a C-index of 0.890 (95% confidence interval [CI]: 0.867-0.914) and 0.864 (95% CI: 0.817-0.911) for the training and external validation cohorts, respectively. Additionally, calibration of the nomogram revealed good predictive ability, as indicated by the Brier score (0.108 and 0.100 for the training and external validation cohorts, respectively). CONCLUSIONS: A nomogram was developed that could compute the probability of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma with good calibration and discrimination. The nomogram has potential as a reliable tool for clinical evaluation and decision-making.

[Evaluation of ocular surface status and function in primary Sjögren's syndrome with hypothyroidism].

OBJECTIVE: To explore the effect of hypothyroidism (HT) on the ocular surface status of patients with primary Sjögren's syndrome-related dry eye (pSS-DED). METHODS: The cross-sectional study included 36 patients with pSS-DED who were treated at the dry eye clinic of Peking University Third Hospital from December 2020 to June 2021, of whom 12 were pSS-DED patients combined with HT. In the same period, 24 patients with simple dry eye disease (DED) were served as a control group. All the patients filled out the Ocular Surface Disease Index (OSDI) questionnaire, and performed tear film break-up time (BUT), Schirmer test, tear meniscus height, corneal/conjunctival fluorescein staining, meibomian gland secretion capacity, meibum evaluation and confocal microscope examination. RESULTS: (1) Compared with pSS-DED and simple DED patients, pSS-DED +HT patients had lower average BUT [(2.7±0.8) s], Schirmer test [(4.9±4.8) mm] and tear meniscus height [(0.13±0.03) mm], and the difference was statistically significant (F=12.43, P < 0.01; F=6.96, P < 0.01; F=3.31, P < 0.05). (2) Compared with DED and pSS-DED patients, the meibomian gland secretion capacity and meibomian trait scores of pSS-DED+HT patients were mainly distributed in the high division. There were statistically significant differences in the distribution of secretion capacity of meibomian glands (χ2=10.72, P < 0.05) and meibomian trait assessment scores (χ2=8.34, P < 0.05) among the three groups. (3) Serum total thyroxine and serum free thyroxine levels in the pSS-DED+HT patients showed positive correlation (P < 0.05, P < 0.05) with their BUT (r=0.60, 0.60), Schirmer's test (r=0.64, 0.66) and tear river height (r=0.61, 0.62), independent of lid gland secretory capacity; no significant correlation was found between thyroid-stimulating hormone, anti-thyroglobulin antibody and lid gland secretory capacity. Thyroid hormone, anti-thyroglobulin antibody, and thyroid peroxidase antibody were not found to be significantly correlated with ocular surface status. (4) Compared with pSS-DED, the fiber density of the subbasal nerve plexus in pSS-DED+HT group decreased (t=2.06, P < 0.05), and the curvature score increased (t=2.13, P < 0.05). CONCLUSION: The ocular surface condition of pSS-DED patients with HT is worse than that of pSS-DED and DED patients. The main manifestations are that tear secretion, tear film stability, secretory function of the meibomian glands, meibum trait and fiber density of the subbasal nerve plexus decrease while the curvature increases. The mechanism might be related to the decrease in thyroid hormone production.

[Functional characteristics of YAP-positive hepatocytes expression in an early stage of NASH with transcriptome sequence analysis].

Objective: To analyze and compare the differentially expressed genes (DEGs) of Yes-associated protein (YAP)-positive and negative hepatocytes and further understand the preliminary functional characteristics of YAP-positive hepatocytes in an early mouse model of nonalcoholic steatohepatitis (NASH) with transcriptome sequence (RNA-Seq). Methods: C57BL/6 mice were fed with methionine-choline deficiency (MCD) diet for 2 weeks to establish an early NASH model, and the control group was fed with normal diet. Liver tissue was stained with hematoxylin-eosin (HE) and Sirius red, and the pathological score was recorded. The expression of YAP and P-YAP were determined by immunohistochemistry (IHC) in liver tissues. Primary hepatocytes with viability greater than 90% were isolated and purified by collagenase perfusion combined with Percoll density gradient centrifugation. YAP-positive and negative hepatocytes were assessed by YAP antibody, flow cytometry and RNA-Seq analyses. Sequencing results were screened by GO, KEGG and interaction network analysis methods. RT-PCR was used to verify the expression levels of YAP and some DEGs in liver tissue model group. Two samples mean was compared by independent samples t-test. Results: Compared with the control group, the HE-stained liver tissue of MCD-induced mice at 2 weeks showed steatosis (pathological score 1.07±0.21), accompanied by lobular inflammation (pathological score 1.13±0.32) and ballooned hepatocyte (pathological score 0.80) ±0.20). Sirius red staining showed non-significant liver fibrosis (pathological score 0.40±0.40). IHC showed partial YAP-positive hepatocytes expression in an early stage of NASH. RNA-Seq analysis showed that clean reads of YAP-positive and negative hepatocytes were 49 310 604 and 5 4820 036, respectively. Compared with YAP-negative hepatocytes, YAP-positive hepatocytes had differential expression of 5 565 genes, including 1 662 up-regulated genes and 3 903 down-regulated genes. GO analysis of up-regulated genes showed that the metabolic processes related to mitochondrial functions, such as purine nucleoside triphosphate and nucleoside triphosphate were significantly enriched in biological processes (BP), while down-regulated gene analysis showed that olfactory-related receptor were significantly enriched in BP. KEGG analysis showed that DEGs were enriched in 292 pathways, and oxidative phosphorylation (OXPHOS) pathway was significantly enriched in signaling pathway. RT-PCR validated that inflammatory factors (interleukin-1ß, interleukin-6), YAP and its target genes (Cyr61, Ankrd1), and Cox5b and Sdhc genes were significantly up-regulated in the OXPHOS pathway, which was consistent with the sequencing results. In addition, eight key genes with interaction network analysis were predicted. Conclusion: Changes in hepatocyte metabolic levels may be associated with increased YAP activity in an early stage of NASH.

[Mechanism and clinical significance of HBV reactivation after anti-HCV therapy].

Direct-acting antivirals (DAAs) can strongly inhibit the replication of hepatitis C virus (HCV) and effectively clear the infection, but it may cause hepatitis B virus (HBV) reactivation, leading to severe liver damage and fulminate hepatitis in patients with HCV/HBV coinfection. In this review, we summarized the different replication process of HCV and HBV in infected hepatocytes and consequent innate immune response, and then discussed the molecular mechanism and clinical significance of HBV reactivation, and put forward the clinical precaution.

[The clinical value of von Willebrand factor and VITRO score in evaluating disease progression in patients with HBV infection].

Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P＜0.01], 0.949 [95% CI: 0.916-0.982, P＜0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P＜0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P＜0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P＜0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.

Opsin 5 is a key regulator of ultraviolet radiation-induced melanogenesis in human epidermal melanocytes.

BACKGROUND: Human skin, which is constantly exposed to solar ultraviolet radiation (UVR), has a unique ability to respond by increasing its pigmentation in a protective process driven by melanogenesis in human epidermal melanocytes (HEMs). However, the molecular mechanisms used by HEMs to detect and respond to UVR remain unclear. OBJECTIVES: To investigate the function and potential mechanism of opsin 5 (OPN5), a photoreceptor responsive to UVR wavelengths, in melanogenesis in HEMs. METHODS: Melanin content in HEMs was determined using the NaOH method, and activity of tyrosinase (TYR) (a key enzyme in melanin synthesis) was determined by the l-DOPA method. OPN5 expression in UVR-treated vs. untreated HEMs and explant tissues was detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence. Short interfering RNA-mediated OPN5 knockdown and a lentivirus OPN5 overexpression model were used to examine their respective effects on TYR, tyrosinase-related protein 1 (TRP1), TRP2 and microphthalmia-associated transcription factor (MITF) expression, under UVR. Changes in expression of TYR, TRP1 and TRP2 caused by changes in OPN5 expression level were detected by RT-qPCR and Western blot. Furthermore, changes in signalling pathway proteins were assayed. RESULTS: We found that OPN5 is the key sensor in HEMs responsible for UVR-induced melanogenesis. OPN5-induced melanogenesis required Ca2+ -dependent G protein-coupled receptor- and protein kinase C signal transduction, thus contributing to the UVR-induced MITF response to mediate downstream cellular effects, and providing evidence of OPN5 function in mammalian phototransduction. Remarkably, OPN5 activation was necessary for UVR-induced increase in cellular melanin and has an inherent function in melanocyte melanogenesis. CONCLUSIONS: Our results provide insight into the molecular mechanisms of UVR sensing and phototransduction in melanocytes, and may reveal molecular targets for preventing pigmentation or pigment diseases.

Effects of the prebiotic inulin-type fructans on post-antibiotic reconstitution of the gut microbiome.

AIMS: Interventions using prebiotic inulin-type fructans (ITFs) are widely prescribed to modulate the gut microbiota composition and activity to promote health. However, the impacts of ITFs on post-antibiotic reconstitution of the gut microbiome remain incompletely understood. The aim of the present study was to investigate the effects of ITFs supplementation on intestinal inflammation, the composition of the intestinal microbiota and the colonic transcriptome after antibiotic treatment. METHODS AND RESULTS: Male BALB/c mice were subjected to an antibiotic cocktail (ABx) treatment for 7 days, and their microbiomes were then reconstituted either spontaneously or with ITFs supplementation (5%) for 14 days. Our data showed that ITFs supplementation delayed the recovery of antibiotic-induced colitis compared with the spontaneous recovery. Neither ITFs supplementation nor spontaneous recovery could restore the microbial community composition at the genus level back to its initial composition. ITFs supplementation increased the relative abundance of some beneficial bacteria and butyrate levels, but resulted in selective blooms of some opportunistic pathogens and elevated the pathways associated with diseases linked to gut microbiota function. Both ITFs supplementation and spontaneous recovery could restore the colonic transcriptome nearly to the initial profile to a certain extent; however, ITFs supplementation delayed the restoration of the immunoglobulin genes compared to spontaneous recovery. CONCLUSION: These data showed that post-antibiotic ITFs consumption did not always lead to beneficial effects but might lead to potential adverse effects in the context of dysbiosis. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings highlighted that caution is required when supplementing ITFs to restore intestinal homeostasis in the context of dysbiosis resulting from broad-spectrum antibiotics.

[The Clinical Significance and Mechanism of the Effect for Hepatitis B Virus Protein on Host Immune].

The cytotoxic effect targeting hepatitis B virus (HBV) infected hepatocytes from virus-specific cytotoxic T cells and the neutralizing antibodies secreted by virus-specific B cells play an important role in the immune control and elimination of HBV. In patients with chronic hepatitis B, the liver immune microenvironment usually presents a suppression state, and virus-specific immune cells are mostly exhausted. Studies on the interaction between HBV and host immunity during infection, especially the influence of various viral proteins on immune cell function, will contribute to understanding the mechanism of the chronicity of HBV infection, disease progression, and optimization of immunotherapy against HBV. The review summarized the suppressive effects of HBV viral proteins on the host innate immunity and adaptive immune system, to help us understanding the mechanism(s) relevant to the observation that a CHB patient with HBeAg loss and lower HBsAg level is more likley achieving functionall cure. and expect to provide new sights for accelerate virus clearance and achieve functional cure of chronic hepatitis B, by removing the HBV viral proteins and consequently, liberting host immune from suppression state.

[Risk assessment of exported risk of COVID-19 from Hubei Province].

Objective: To evaluate the exported risk of COVID-19 from Hubei Province and the imported risk in various provinces across China. Methods: Data of reported COVID-19 cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. Results: A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative COVID-19 cases of provinces was positively correlated with the migration index derived from Hubei Province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). Conclusion: The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.

[Progress in the clinical diagnosis and treatment of hepatic vascular diseases].

The liver has a very special dual blood supply, including the portal vein (65%~75%) and hepatic artery (25%~35%). The hepatic veins returns blood to the systemic circulation via the portal vein, and hepatic artery after hepatic sinusoidal confluence. The lesions on the hepatic vein and its branches can cause ischemia and hypoxia or obstruction of the drainage system, portal hypertension, upper gastrointestinal variceal bleeding, hepatic encephalopathy, and so on. Clinically, hepatic vascular diseases are relatively rare, so the diagnosis and treatment are relatively difficult. Herein, we review the diseases related to the hepatic vascular system.

[Value of serum alpha-fetoprotein for the prognostic evaluation of hepatitis B virus-related acute-on-chronic liver failure treated with artificial liver].

Objective: To investigate the value of alpha-fetoprotein (AFP) level on survived hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients treated with artificial liver. Methods: Clinical indicators of HBV-ACLF patients who were previously treated with plasma exchange-based artificial liver at our department were retrospectively collected. The difference of serum AFP level between the survival and the death group was compared at 30, 90 and 180 days after artificial liver treatment. The ROC curves of the subjects were plotted, and the sensitivity and specificity of AFP for the survival prediction of the patients at 30, 90 and 180 days after artificial liver surgery were calculated. AFP was divided into a high AFP group and a low AFP group using median value. AFP and postoperative survival predictive value at 30, 90, and 180 days were analyzed. Results: A total of 93 cases were included in this study. The AFP of the survival group at 30, 90, and 180 days was (231.0 ± 286.2) ng / ml, (237.69 ± 297) ng / ml, (229.44 ± 286.46) ng/ml, and the death group was (76.4 ± 104.7) ng/ml, (103.13 ± 116.99) ng / ml, (136.34 ± 2.9.29) ng/ml, respectively. AFP of the death group was significantly lower than the corresponding survival group (P < 0.05). Receiver operating characteristic (ROC) curve analyses indicated that the area under the curve (AUC) and its 95% confidence interval at 30, 90, and 180 days after artificial liver surgery were 0.739 (0.611 ~ 0.867), 0.675 (0.550 ~ 0.80), 0.653 (0.524 ~ 0.781), respectively. The median serum AFP value was 110 ng/ml, and the survival analysis showed that the survival time of the high AFP group was significantly higher than the low AFP group at 30 d (P = 0.01), 90 d (P = 0.04) and 180 d (P = 0.03) after artificial liver surgery. Conclusion: Serum AFP can be used as a predictor of survival for HBV-ACLF patients after artificial liver therapy and its clinical value needs to be further verified by the larger sample size.

Increased intrinsic connectivity for structural atrophy and functional maintenance after acute ischaemic stroke.

BACKGROUND AND PURPOSE: Significant clinical recovery has commonly been observed in ischaemic stroke patients with irreversible brain structural damage. However, brain mechanisms that help to maintain clinical function remain unclear. METHODS: Sixty-two patients with acute ischaemic stroke underwent longitudinal clinical assessments and magnetic resonance scanning. The clinical recovery trajectory was evaluated using a hierarchical linear model and intrinsic connectivity was analysed with a seed-based approach to examine its changing pattern based on the regional volume changes calculated using voxel-wise analysis. RESULTS: It was observed that clinical outcome measures improved mainly in the short-term period (baseline versus 3 weeks) and then remained stable. Grey matter volume was reduced significantly in the bilateral caudate over the entire 3-year long-term period. Significant intrinsic connectivity increases were observed in the caudate-middle cingulum over the short-term period and in the caudate-precuneus and caudate-calcarine over the long-term period. Finally, it was found that increased caudate-calcarine connectivity was associated with reduced right caudate volume, and a positive correlation was found between increased caudate-middle cingulum connectivity and the amount of modified Rankin score changes. CONCLUSIONS: The increased intrinsic connectivity found in this study tends to be a compensatory mechanism for post-stroke structural damage, associated with clinical recovery. The study helps in understanding the significance of enhanced intrinsic connectivity in post-stroke long-term assessment and rehabilitation.

The mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target.

BACKGROUND: Opioid receptors are implicated in cancer progression and long-term patient outcomes. However, the prognostic significance, underlying mechanisms, and therapeutic value of mu-opioid receptor (MOP) in hepatocellular carcinoma (HCC) remain unclear. METHODS: MOP expression in human biopsy HCC samples was evaluated using RNA microarrays, quantitative real-time polymerase chain reaction (qRT-PCR), and immunochemical analyses. Molecular and cellular techniques, including siRNA-mediated depletion and lentiviral vector-mediated overexpression, were used to elucidate the functions and mechanisms of MOP. The effect of the MOP agonist morphine in HCC was evaluated both in vitro and in vivo. The therapeutic value of MOP inhibitors in HCC progression and metastasis was investigated with in vitro experiments and subcutaneous and orthotopic HCC mouse models in vivo. RESULTS: Through microarray analysis and qRT-PCR, we identified that MOP is highly expressed in human HCC tumours. High MOP expression in HCC tumours was confirmed by immunocytochemistry and correlated with aggressive clinicopathological features and a worse prognosis. Depletion of MOP suppressed cell proliferation, migration, and invasion, whereas overexpression of MOP promoted cell growth and metastasis in human HCC cell lines. Both clinical and biological evidence revealed that MOP-mediated epithelial-mesenchymal transition promotes HCC metastasis and poor prognosis. Morphine promotes cell proliferation, migration, and invasion in vitro and in vivo in mouse models. More importantly, MOP inhibitors suppressed cell growth, invasion, and metastasis in vitro and in the subcutaneous and orthotopic xenograft models. CONCLUSIONS: MOP plays a key oncogenic function in hepatocarcinogenesis. Its overexpression is associated with poor prognosis in patients with HCC. Furthermore, MOP inhibitors may be a promising strategy for HCC therapy.