Metabolomic and structural brain connectomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder

OBJECTIVE Major depressive disorder(MDD) is a highly heterogeneous mental illness.Further classification may help characterize its heterogeneity.The purpose of this study was to examine metabolomic and brain connectomic associations with traditional Chinese medicine(TCM) diagnostic classification of MDD.METHODS Fifty unmedicated depressed patients were classified into Liver Qi Stagnation(LQS,n=30) and Heart and Spleen Deficiency(HSD,n=20) subtypes according to TCM diagnosis.Healthy volunteers(n=28) were included as controls.Gas chromatography-mass spectrometry(GC-MS) and diffusion tensor imaging were used to detect serum and urinary metabolomic profiles and whole-brain white matter connectivity,respectively.RESULTS In metabolomic analysis,28 metabolites were identified for good separations between TCM subtypes and healthy controls in serum and urine samples.While both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids and energy metabolism-related metabolites that were differentiated from healthy controls,the LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in the biosynthesis of monoamine and amino acid neurotransmitters.Several metabolites are differentially associated with the two subtypes.In connectomic analysis,The LQS subtype showed significant differences in multiple network metrics of the angular gyrus,middle occipital gyrus,calcarine sulcus,and Heschl′ s gyrus when compared to the other two groups.The HSD subtype had markedly greater regional connectivity of the insula,parahippocampal gyrus,and posterior cingulate gyrus than the other two groups,and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole.The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity.CONCLUSION The LQS subtype may represent an MDD subpopulation mainly characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters,closer associations with stress-related pathophysiology,and aberrant connectivity of the audiovisual perception-related temporal-occipital network,whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbicparalimbic network.Certain metabolomic and connectomic variables are potential biomarkers for TCM diagnostic subtypes which is perhaps an alternative classification for depressive disorders.

Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

Potential role of Lycium barbarum polysaccharides in glaucoma management:evidence from preclinical in vivo studies

In recent years,the pharmacological benefits of herbal extracts have been revisited for their potential neuroprotective effects in glaucoma.The polysaccharides extracted from the fruits of Lycium barbarum L.,or Lycium barbarum polysaccharides,exert their anti-aging effect through reducing oxidative stress,modulating the immune response,enhancing neuronal responses,and promoting cytoprotection.The therapeutic efficacy of Lycium barbarum polysaccharides in preserving retinal ganglion cells and their functions was demonstrated in a range of experimental models of optic neuropathies.These include the acute and chronic ocular hypertension models,the partial optic nerve transection model,and the ischemic-reperfusion injuries model.Based on these findings,Lycium barbarum polysaccharides appear to be a good candidate to be developed as a neuroprotective agent for treating multifactorial diseases.This review aims to present a comprehensive review on the latest preclinical evidence on the pre-and post-treatment benefits of Lycium barbarum polysaccharides in retinal ganglion cell neuroprotection.The possible mechanisms of Lycium barbarum polysaccharides mediating retinal ganglion cell neuroprotection will also be described.Moreover,the potential research gaps in the effective translation of Lycium barbarum polysaccharides treatment into clinical glaucoma management will be discussed.

Comparison of ocular biometry in Chinese patients using two swept-source optical coherence tomography devices

Background:To compare two swept-source optical coherence tomography(SS-OCT)biometers,IOLMaster 700 and ANTERION.Methods:This is a retrospective study.Biometric measurements of cataract patients performed between March and July 2021 in the Department of Ophthalmology,United Christian Hospital,Hong Kong,were reviewed.Patients scheduled for cataract surgery were measured with both SS-OCT devices on the same day.The following biometry parameters were compared:keratometry(K),total keratometry(TK),axial length(AL),central corneal thickness(CCT),anterior chamber depth(ACD),lens thickness(LT),white-to-white(WTW)and the predicted intraocular lens(IOL)power to achieve emmetropia.To assess the agreement between the devices,Bland-Altman analysis with 95%limits of agreement(LoA)were used.Results:In total,92 eyes of 47 subjects were measured with both devices.There were statistically significant differences between the two biometers for most measurements(P<0.05)except for flat K,AL and IOL power when using the right eyes for analysis.For the left eyes,there were statistically significant differences in the measurements from the two biometers in all parameters except for flat and steep K.The ANTERION did not obtain ACD,AL and LT in 2(2.17%),1(1.09%)and 5 cases(5.43%)respectively.Conclusions:The two biometers showed a clinically acceptable agreement in most parameters.Comparisons showed significant differences in most parameters but not clinically relevant except for the TK and WTW,and these two parameters should not be used interchangeably between the devices.

Dissolvable temporary barrier:a novel paradigm for flexible hydrogel patterning in organ-on-a-chip models

A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as organ-on-a-chipmodels.The hydrogel patterningwith awell-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a boundary.However,these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo conditions.Herein,we present a novel dissolvable temporary barrier(DTB)strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular hydrogels.The key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology,followed by a barrier-free medium perfusion after the dissolution of the DTB.Single and multiple tissue compartments with different geometries can be established using either straight or curved DTB structures.The effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor model.As a new proof-of-concept in vasculature-on-a-chip,DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices,which is an improved protocol for the fabrication ofmultiorgan chips.Therefore,we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.

Lycium barbarum polysaccharides related RAGE and Aβ levels in the retina of mice with acute ocular hypertension and promote maintenance of blood retinal barrier

Our previous study verified the protective effects of Lycium barbarum polysaccharides(LBP)on retinal neurons and blood vessels in acute ocular hypertension(AOH)mice.To investigate the effect of LBP on the reactivity of retinal glial cells,an AOH mouse model was established in one eye by maintaining ocular hypertension of 90 mm Hg for 60 minutes.Either LBP solution(1 mg/kg)or phosphate-buffered saline was administrated to the mice by gavage daily,starting 7 days before the AOH insult and continuing until the mice were sacrificed for specimen collection on day 4 post-insult.After AOH insult,increased numbers of astrocytes and microglia were observed,together with decreased expression of the following glial cell biomarkers in the retinal ganglion cells of AOH mice:glial fibrillary acidic protein,glutamine synthetase,aquaporin-4,S-100 proteins,ionized calcium-binding adaptor molecule 1,amyloid precursor protein and receptor of advanced glycosylation end-products.After intervention with LBP,the above changes were significantly reduced.Remarkably,morphological remodeling of blood vessel-associated retinal astrocytes,marked by glial fibrillary acidic protein,was also observed.These results,taken together,suggest that LBP regulated the production of amyloid-βand expression of receptor of advanced glycosylation end-products,as well as mediating the activity of retinal glial cells,which may lead to the promotion of better maintenance of the blood-retinal barrier and improved neuronal survival in AOH insult.This study was approved by the Committee for the Use of Live Animals in Teaching and Research(approval No.CULTRA-#1664-08).

Improvement in quality of life in depressed patients following verum acupuncture or electroacupuncture plus paroxetine:A randomized controlled study of 157 cases

Depressed patients with scores of 17 or more on the 17 items of the Hamilton Depression Rating Scale were treated with the antidepressant drug paroxetine. They also underwent verum acupuncture or electroacupuncture at Baihui （GV20） and Yintang （GV29）. The World Health Organization Quality of Life Scale Brief Version showed a significant increase in the total scores of patients who underwent verum acupuncture and electroacupuncture for 6 weeks compared with those who were given paroxetine only; significantly increased physical domain and social relationship scores in verum acupuncture patients compared with paroxetine only; and significantly elevated psychological domain scores with electroacupuncture compared with paroxetine only. These results indicate that both verum acupuncture and electroacupuncture can improve quality of life in depressed patients undergoing paroxetine treatment,

Comparison of surgical outcome of trabeculectomy and phacotrabeculectomy in Chinese glaucoma patients

Our study retrospectively reviewed the surgical outcomes up to 3 mo of 38 consecutive Chinese glaucoma patients who underwent trabeculectomy（n=18） or phacotrabeculectomy（n=20）.Baseline age,visual acuity,and intraocular pressure were comparable.Intraocular pressure from post-operative 1 d to 3 mo were similar between 2 groups.Complete success was achieved in 65% of phacotrabeculectomy,and 66.7% of trabeculectomy cases;while failure occurred in 16.7% of phacotrabeculectomy,and 10% of trabeculectomy cases at 3 mo.Phacotrabeculectomy group consistently showed better improvement in visual acuity.Diffuse blebs occurred in 65% of phacotrabeculectomy and 83% of trabeculectomy eyes;and flat blebs in 35% of phacotrabeculectomy,but none after trabeculectomy.There was more hypotony（5% vs 0） after phacotrabeculectomy.To conclude,phacotrabeculectomy and trabeculectomy demonstrated comparable intraocular pressure control up to 3 mo post-operatively.However,phacotrabeculectomy patients had better visual acuity improvement.Nonetheless,more diffuse bleb and less hypotony were present following trabeculectomy.

Effects of low level laser treatment on the survival of axotomized retinal ganglion cells in adult Hamsters

Injury to axons close to the neuronal bodies in the mammalian central nervous system causes a large proportion of parenting neurons to degenerate. It is known that optic nerve transection close to the eye in rodents leads to a loss of about half of retinal ganglion cells in 1 week and about 90% in 2 weeks. Using low level laser treatment in the present study, we demonstrated that treatment with helium-neon （660 nm） laser with 15 mW power could delay retinal ganglion cell death after optic nerve axotomy in adult hamsters. The effect was most apparent in the ifrst week with a short period of treatment time （5 minutes） in which 65–66% of retinal ganglion cells survived the optic nerve axotomy whereas 45–47% of retinal ganglion cells did so in optic nerve axotomy controls. We also found that single dose and early commencement of laser irradiation were important in protecting retinal ganglion cells following optic nerve axotomy. These ifndings thus convincingly show that appropriate laser treatment may be neuroprotective to retinal gan-glion cells.

Rare complication of inflammatory bowel disease-like colitis from glycogen storage disease type 1b and its surgical management:A case report

BACKGROUND Glycogen storage disease(GSD)is an autosomal recessive inborn metabolic disorder.Patients with GSD are prone to hypoglycaemia,hyperlactacidemia and bleeding.GSD type 1b(GSD-1b)patients specifically can develop neutropenia,recurrent bacterial infection and inflammatory bowel disease(IBD).Documentation of the long-term outcomes of surgical management of GSD-1b has been scarce,especially for Asian patients.We herein describe a case of GSD-1b complicated by IBD-like colitis and coloduodenal fistula.The patient was managed successfully with surgical intervention.CASE SUMMARY A 20-year-old Chinese lady confirmed by genetic testing to have GSD-1b was initially managed with uncooked cornstarch and granulocyte-colony stimulating factor.With recurrent abdominal symptoms,her condition was treated as clinical“Crohn’s disease”with mesalazine,prednisolone and azathioprine conservatively.Colonoscopy showed a tight stricture at the hepatic flexure.Subsequent computerized tomographic colonography revealed a phlegmon at the ileocaecal region with a suspected coloduodenal fistula.Eventually an exploratory laparotomy was performed and severe colitis at the ascending colon with coloduodenal fistula was confirmed.Right hemicolectomy with primary anastomosis and repair of the duodenum were performed.Surgical management of complications from GSD-1b associated IBD-like colitis has rarely been described.First-line treatment would usually be conservative.Surgical intervention like hemicolectomy is mainly reserved for refractory cases.CONCLUSION Surgical management of coloduodenal fistula in GSD-1b patients is a feasible and safe option when failed conservative management.

Self-assembling peptide nanofibrous hydrogel as a promising strategy in nerve repair after traumatic injury in the nervous system

Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.The proliferation of a large number of astrocytes results in the formation of glial scar.

Low dose of corticosterone treatment with exercise increases hippocampal cell proliferation, and improves cognition

Intermediate level of stress is beneficial for brain functions, whereas extreme low level or high level of stress is deleterious. We have previously shown that chronic exposure to high doses of corticosterone （CORT） suppressed hippocampal plasticity and physical exercise in terms of running counteracted the detrimental effects of CORT treatment. We aimed to study whether a mild stress, that mimicked by a treatment with low CORT dose, improved hippocampal plasticity in terms of hippocampal cell proliferation and dendritic remodeling, and to examine whether running with CORT treatment showed an additive effect on improving hippocampal plasticity. The rats were treated with 20 mg/kg CORT for 14 days with or without running, followed by Morris water maze test or forced swim test. The hippocampal proliferating cells was labeled by intraperitoneal injection of 5-bromo-2＇-deoxyuridine. The dendritic morphology was analyzed using Golgi staining method. Treatment with 20 mg/kg CORT alone yielded a higher number of hippocampal cell proliferation and significantly increased dendritic branching compared to vehicle-treated non-runners, but had no behavioral effects. In contrast, CORT treatment with running showed an additive increase in hippocampal cell proliferation and dendritic remodeling that was associated with improved spatial learning and decreased depression-like behavior; however, there was no additive improvement in behavior compared to vehicle-treated runners. These findings suggest that mild stress does not always cause detrimental effect on the brain, and combining mild stress with running could promote hippocampal plasticity via inducing cell proliferation and dendritic remodeling.

Comparison of electroretinographic responses between two different age groups of adult Dark Agouti rats

AIM: To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function. METHODS: The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n =8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a -wave, b -wave, photopic a -wave, b -wave and photopic negative response (PhNR) were compared between groups. RESULTS: The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a -wave and b wave, photopic b -wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats. CONCLUSION: In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age -related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats.

Self-harm attempters' perception of community services and its implication on service provision

Objective:This study aimed at exploring the attempters'perception of community social services included any barriers to seeking help and services.Method:The participants were patients with self-harming behavior aged 15 years or above.A set of guiding questions were designed to explore the general barriers and accessibility to community social services.A voice recording was made,which was later converted into a text transcript and then preceded for content analysis with co-occurrence and similarity matrix interpretation.Two males and nine females with a history of self-harm aged between 24 and 58 years were recruited for the interviews.Result:The participants had diverse experiences and backgrounds,and attitudes toward community social services.However,there was a shared perception of the need to enhance community social services.There were four main themes and 12 sub themes identified.The main theme included the service availability,service accessibility,affordability and acceptability.For details,participants were unaware of the available types of care/social services in the community,and were unaware about the nearby social services.They also suggested extending service hours and focused services should be offered to help people with different backgrounds and needs.Actually,those with experience of service utilization had both positive and negative perspectives and they gave suggestions for service delivery,mainly extending service hours and offering focused services such as for gambling control and financial planning.In view of interaction with service providers,counseling skills and trust were highly appreciated by the participants.Conclusion:The results identified common circumstances of falling into financial hardship(gambling)and social fragmentation(divorce,poor family relationships,and poor marital relationships),which also suggested to enhance services on center location,service arrangement,and skill of caregivers.

Virome-wide analysis of histone modification mimicry motifs carried by viral proteins

Histone mimicry(HM)refers to the presence of short linear motifs in viral proteins that mimic critical regions of host histone proteins.These motifs have the potential to interfere with host cell epigenome and counteract antiviral response.Recent research shows that HM is critical for the pathogenesis and transmissibility of influenza virus and coronavirus.However,the distribution,characteristics,and functions of HM in eukaryotic viruses remain obscure.Herein,we developed a bioinformatic pipeline,Histone Motif Scan(HiScan),to identify HM motifs in viral proteins and predict their functions in silico.By analyzing 592,643 viral proteins using HiScan,we found that putative HM motifs were widely distributed in most viral proteins.Among animal viruses,the ratio of HM motifs between DNA viruses and RNA viruses was approximately 1.9:1,and viruses with smaller genomes had a higher density of HM motifs.Notably,coronaviruses exhibited an uneven distribution of HM motifs,with betacoronaviruses(including most human pathogenic coronaviruses)harboring more HM motifs than other coronaviruses,primarily in the NSP3,S,and N proteins.In summary,our virome-wide screening of HM motifs using HiScan revealed extensive but uneven distribution of HM motifs in most viral proteins,with a preference in DNA viruses.Viral HM may play an important role in modulating viral pathogenicity and virus-host interactions,making it an attractive area of research in virology and antiviral medication.

Comparison of systematic and combined biopsy for the detection of prostate cancer

Systematic prostate biopsy has limitations,such as overdiagnosis of clinically insignificant prostate cancer and underdiagnosis of clinically significant prostate cancer.Magnetic resonance imaging(MRI)-guided biopsy,a promising alternative,might improve diagnostic accuracy.To compare the cancer detection rates of systematic biopsy and combined biopsy(systematic biopsy plus MRI-targeted biopsy)in Asian men,we conducted a retrospective cohort study of men who underwent either systematic biopsy or combined biopsy at two medical centers(Queen Mary Hospital and Tung Wah Hospital,Hong Kong,China)from July 2015 to December 2022.Descriptive statistics were calculated,and univariate and multivariate logistic regression analyses were performed.The primary and secondary outcomes were prostate cancer and clinically significant prostate cancer.A total of 1391 participants were enrolled.The overall prostate cancer detection rates did not significantly differ between the two groups(36.3%vs 36.6%,odds ratio[OR]=1.01,95%confidence interval[CI]:0.81-1.26,P=0.92).However,combined biopsy showed a significant advantage in detecting clinically significant prostate cancer(Gleason score≥3+4)in patients with a total serum prostate-specific antigen(tPSA)concentration of 2-10 ng ml−1(systematic vs combined:11.9%vs 17.5%,OR=1.58,95%CI:1.08-2.31,P=0.02).Specifically,in the transperineal biopsy subgroup,combined biopsy significantly outperformed systematic biopsy in the detection of clinically significant prostate cancer(systematic vs combined:12.6%vs 24.0%,OR=2.19,95%CI:1.21-3.97,P=0.01).These findings suggest that in patients with a tPSA concentration of 2-10 ng ml−1,MRI-targeted biopsy may be of greater predictive value than systematic biopsy in the detection of clinically significant prostate cancer.

An update on hormonal regulation of early embryo-fallopian tube interactions: insights for improvements of assisted reproductive technology outcomes

Human fallopian tubes(FTs)play important roles in the whole reproductive process.FTs are the site for the final maturation of gametes,fertilization,transport of preimplantation embryos,and early embryonic development before entering the uterus.All these functions are critical in the establishment of a successful pregnancy.When the embryo is in transit through the FT,the FT microenvironment changes through endocrine,paracrine,autocrine,and juxtacrine mechanisms which involve various hormones and bioactive substances mainly from the neighboring cells.Therefore,the interactions between the embryo and the FT may be the earliest embryo-maternal communications that are essential for the establishment of pregnancy.This review critically discusses the evidence of various hormonal and bioactive mediated control of the microenvironment in the FTs during the earliest embryo-maternal communications.Moreover,we highlight existing gaps in the knowledge and the importance of exploring more of the physiology of FTs which will hold the key to producing high-quality embryos for patients seekingin vitro fertilization(IVF)treatments.

Significance of radiation esophagitis:Conditional survival assessment in patients with non-small cell lung cancer

Purpose:This study aimed to examine the effect of radiation esophagitis(RE)and the dynamics of RE on subse-quent survival in non-small cell lung cancer(NSCLC)patients who underwent radiotherapy.Experimental Design:Patients with NSCLC treated with fractionated thoracic radiotherapy enrolled in prospective trials were eligible.RE was graded prospectively according to Common Terminology Criteria for Adverse Events(CTCAE)v3.0 per protocol requirement weekly during-RT and 1 month after RT.This study applied conditional survival assessment which has advantage over traditional survival analysis as it assesses the survival from the event instead of from the baseline.P-value less than 0.05 was considered to be significant.The primary endpoint is overall survival.Results:A total of 177 patients were eligible,with a median follow-up of 5 years.The presence of RE,the maximum RE grade,the evolution of RE and the onset timing of RE events were all correlated with subsequent survival.At all conditional time points,patients first presented with RE grade1(initial RE1)had significant inferior subsequent survival(multivariable HRs median:1.63,all P-values<0.05);meanwhile those with RE progressed had significant inferior subsequent survival than those never develop RE(multivariable HRs median:2.08,all P-values<0.05).Multivariable Cox proportional-hazards analysis showed significantly higher C-indexes for models with inclusion of RE events than those without(all P-values<0.05).Conclusion:This study comprehensively evaluated the impact of RE with conditional survival assessment and demonstrated that RE is associated with inferior survival in NSCLC patients treated with RT.

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse(ARFI), aspartate aminotransferase to platelet ratio index(APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B(CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage(all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI(P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage(Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI(Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

AIM Infantile-onset inflammatory bowel disease(IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10(IL-10) and interleukin-10 receptors(IL-10R) in Asian children with IO-IBD. METHODS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10 R genes in patients with presenting clinical features of Crohn's disease(CD).RESULTS Six [13%; CD = 3, ulcerative colitis(UC) = 2, IBDunclassified(IBD-U) = 1] of the 48 children(CD = 25; UC = 23) with IBD have IO-IBD. At final review [median(range) duration of follow-up: 6.5(3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy(IBD-U), after standard immunosuppression(CD), and after total colectomy(UC)]. Three patients were on immunosuppression:one(UC) was in remission while two(both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea(100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease(0% vs 19%, P = 0.31), requiring biologics therapy(50% vs 36%, P = 0.40), surgery(50% vs 29%, P = 0.27), or achieving remission(50% vs 64%, P = 0.40). No mutations in either IL10 or IL10 R in the three patients with CD and the only patient with IBD-U were identified.CONCLUSION The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10 R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.