Artificial intelligence for disease diagnostics still has a long way to go

Artificial intelligence(AI)can sometimes resolve difficulties that other advanced technologies and humans cannot.In medical diagnostics,AI has the advantage of processing figure recognition,especially for images with similar characteristics that are difficult to distinguish with the naked eye.However,the mechanisms of this advanced technique should be well-addressed to elucidate clinical issues.In this letter,regarding an original study presented by Takayama et al,we suggest that the authors should effectively illustrate the mechanism and detailed procedure that artificial intelligence techniques processing the acquired images,including the recognition of non-obvious difference between the normal parts and pathological ones,which were impossible to be distinguished by naked eyes,such as the basic constitutional elements of pixels and grayscale,special molecules or even some metal ions which involved into the diseases occurrence.

Protective effects of Lingguizhugan decoction on amyloid-beta peptide (25-35)-induced cell injury Anti-inflammatory effects

In the present study, a human neuroblastoma cell line （SH-SY5Y） and BV-2 microglia were treated with amyloid-β peptide （25-35）, as a model of Alzheimer＇s disease, to evaluate the protective effects of 10-3-10-8 g/mL Lingguizhugan decoction and to examine the underlying anti-inflammatory mechanism. Lingguizhugan decoction significantly enhanced the viability of SH-SY5Y cells with amyloid-β peptide-induced injury, and lowered levels of interleukin-1β, interleukin-6, tumor necrosis factor-a and nitric oxide in the culture supernatant of activated BV-2 microglia. The effects of 103 g/mL Lingguizhugan decoction were more significant. These results suggest that Lingguizhugan decoction can protect SH-SY5Y cells against amyloid-β peptide （25-35）-induced injury in a dose-dependent manner by inhibiting overexpression of inflammatory factors by activated microglia.

Inhibitory effect of Tong Xie-Yao Fang formula on colonic contraction in rats

AIM:To investigate the pharmacological effect ofTong Xie-Yao Fang(TXYF)formula and its underlying mechanisms.METHODS:A neonatal maternal separation plus restraint stress(NMS+RS)model of diarrheapredominant irritable bowel syndrome was developed by subjecting male Sprague-Dawley rats to daily maternal separation from postnatal days 2 to 21 plus restraint stress from days 50 to 59.Rats were randomly divided into two groups(NMS+RS and TXYF formula),and rats with no handling or separation were used as normal controls.Starting from postnatal day 60,rats were administered TXYF formula(9.84 g/100 g body weight)orally twice daily for 14 consecutive days,while the normal and NMS+RS groups were given distilled water.The distinctions of movement index(MI,area under the curve of contraction intensity/min,mg/min)and contraction frequency(CF,number of contractions/min,times/min)of isolated colonic longitudinal smooth muscle strips(CLSMs)in the three groups before and after treatment were observed with a Power Lab system.Different inhibitors were applied,and then 10-4mol/L acetylcholine chloride(Ach)was added to CLSMs to induce muscle contraction.RESULTS:Before treatment,the MI of CLSMs in the NMS+RS and TXYF formula groups was similar and both higher than that in the normal group(545.49±73.66 mg/min vs 245.76±34.44 mg/min and551.09±54.29 mg/min vs 245.76±34.44 mg/min,P<0.01,respectively).After treatment,the MI in the TXYF formula group was lower than that in the NMS+RS group(261.39±38.59 mg/min vs 533.9±61.63 mg/min,P<0.01).In the same way,the CF of CLSMs in the NMS+RS and TXYF formula groups was similar and both higher than that in the normal group(3.42±0.25 times/min and 3.31±0.21 vs1.1±0.17 times/min,P<0.01)before treatment.After treatment,the CF in the TXYF formula group was lower than that in the NMS+RS group(1.42±0.87 times/min vs 3.11±0.82 times/min,P<0.01)and similar to that in the normal group(1.42±0.87 times/min vs 1.09±0.13 times/min).When8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride and 4-aminopyridine were added to the bath and equilibrated for 30 min,respectively,and10-4 mol/L Ach was added to CLSMs to induce muscle contraction,MI of the CLSMs in the TXYF formula group was lower than that in the normal group(666±36.32 mg/min vs 747.77±49.47 mg/min,and 686.53±39.17 mg/min vs 750.45±29.39 mg/min;P<0.01,respectively).The MI of CLSMs in the TXYF formula group was lower than that in the normal group after treatment with nifedipine(689.48±30.84 mg/min vs741.65±32.41 mg/min;P<0.05).CONCLUSION:TXYF formula inhibits colon contraction in rats.This may be related to activation of specific potassium channels and inhibition of extracellular calcium internal flow.

Buyang Huanwu Decoction fraction protects against cerebral ischemia/reperfusion injury by attenuating the inflammatory response and cellular apoptosis

Buyang Huanwu Decoction fraction extracted from Buyang Huanwu Decoction contains saponins of Astragalus, total paeony glycoside and safflower flavones. The aim of this study was to demonstrate the neuroprotective effect and mechanism of Buyang Huanwu Decoction fraction on ischemic injury both in vivo and in vitro. In vivo experiments showed that 50-200 mg/kg Buyang Huanwu Decoction fraction reduced infarct volume and pathological injury in ischemia/reperfusion rats, markedly inhibited expression of nuclear factor-KB and tumor necrosis factor-a and promoted nestin protein expression in brain tissue. Buyang Huanwu Decoction fraction （200 mg/kg） exhibited significant effects, which were similar to those of 100 mg/kg Ginkgo biloba extract. In vitro experimental results demonstrated that 10-100 mg/L Buyang Huanwu Decoction fraction significantly improved cell viability, decreased the release of lactate dehydrogenase and malondialdehyde levels, and inhibited the rate of apoptosis in HT22 cells following oxygen-glucose deprivation. Buyang Huanwu Decoction fraction （100 mg/L） exhibited significant effects, which were similar to those of 100 mg/L Ginkgo biloba extract. These findings suggest that Buyang Huanwu Decoction fraction may represent a novel, protective strategy against cerebral ischemia/reperfusion injury in rats and oxygen-glucose deprivation-induced damage in HT22 cells in vitro by attenuating the inflammatory response and cellular apoptosis.

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

AIM： To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS： Fifty SD rats were divided into control group （n=20） and model group （n=30）. Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole （1 000：250：3）. Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid （HA）, type IV collagen （COW） and laminin （LN） were determined by radioimmunoassay. Liver tissue was fixed in formalin （10%） and 6-μm thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polydonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS： The diameter （2.207 ± 0.096 vs 1.528±0.054 mm, P〈0.01） and pressure （11.014±0.395 vs 8.533±0.274 mmHg, P〈0.01） of portal vein were significantly higher in model group than those in the control group. Plasma HA （129.97±16.10 vs 73.09±2.38 ng/mL, P〈0.01）, ColⅣ （210.49±4.36 vs 89.65±4.42 ng/mL, P〈0.01） and LN （105.00±7.29 vs 55.70±4.32 ng/mL, P〈0.01） were upregulated in model group. Abundant collagen deposited around the central vein of Iobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ. Immunohistochemical staining showed that ColⅣ protein level （0.130±0.007 vs 0.032±0.004, P〈0.01） and LN protein level （0.152±0.005 vs 0.029±0.005, P〈0.01） were up-regulated remarkably in model group. MMP-2 protein expression （2.306±1.089 vs 0.612±0.081, P〈0.01） and TIMP-1 protein expression （3.015±1.364 vs 0.446±0.009, P〈0.01） in freshly isolated hepatic nonparenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression （2.669±0.170 vs 1.695±0.008, P〈0.05）. CONCLUSION： Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcoholinduced portal hypertension in rats,

Corepressor metastasis-associated protein 3 modulates epithelial-to-mesenchymal transition and metastasis

Worldwide,metastasis is the leading cause of more than 90%of cancer-related deaths.Currently,no specific therapies effectively impede metastasis.Metastatic processes are controlled by complex regulatory networks and transcriptional hierarchy.Corepressor metastasis-associated protein 3(MTA3)has been confirmed as a novel component of nucleosome remodeling and histone deacetylation(NuRD).Increasing evidence supports the theory that,in the recruitment of transcription factors,coregulators function as master regulators rather than passive passengers.As a master regulator,MTA3 governs the target selection for Nu RD and functions as a transcriptional repressor.MTA3dysregulation is associated with tumor progression,invasion,and metastasis in various cancers.MTA3 is also a key regulator of E-cadherin expression and epithelial-to-mesenchymal transition.Elucidating the functions of MTA3 might help to find additional therapeutic approaches for targeting components of NuRD.

Diwu Yanggan Modulates the Wnt/β-catenin Pathway and Inhibits Liver Carcinogenesis Signaling in 2-AAF/PH Model Rats

The activation of the Wnt/β-catenin signaling pathway in oval cells after liver injury is implicated in hepatocarcinogenesis.Diwu Yanggan capsule is a Chinese herbal medicine that has been used for treating liver disorder.The present study aimed to examine the mechanism by which Diwu Yanggan inhibits liver carcinogenesis,and the involvement of the Wnt/β-catenin signaling pathway.Diwu Yanggan capsule was administered to 2-acetaminofluorene/partial hepatectomy(2-AAF/PH)rats,a murine model of liver injury.The biomarkers of oval cells and key proteins in the Wnt/p-catenin signaling pathway were assessed on postoperative day 8,10,14,17,19 and 22.The results showed that treatment with Diwu Yanggan was associated with reduced expression of oval cell and stem cell biomarkers in the 2-AAF/PH animals.The expression pattern of key proteins in the Wnt/β-catenin pathway was altered in Diwu Yanggan-treated animals,indicating that the Diwu Yanggan treatment accelerated the activation of the Wnt/β-catenin pathway in the initial stage and contributed to its deactivation in the later stage.Histological findings indicated that hepatocyte proliferation was suppressed in Diwu Yanggan-treated animals,compared with untreated 2-AAF/PH animals.Taken together,Diwu Yanggan capsule may reduce the risk of hepatocarcinogenesis by modulating the Wnt/β-catenin signaling pathway.

Optimal Formula of Angelica sinensis Ameliorates Memory Deficits in β-amyloid Protein-induced Alzheimer's Disease Rat Model

Objective:Angelica(A.)sinensis is used as a traditional medical herb for the treatment of neurodegeneration,aging,and inflammation in Asia.A.sinensis optimal formula(AOF)is the best combination in A.sinensis that has been screened to rescue the cognitive ability in P-amyloid peptide(Ap25-35)-treated Alzheimer’s disease(AD)rats.The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms.

Heavy Metal Assessment among Chinese Nonferrous Metal-exposed Workers from the Jinchang Cohort Study

Environmental exposure to heavy metals has been linked to a wide range of human health hazards. We detected the levels of 15 metals in urine samples from 500 representative sub-samples in an ongoing occupational cohort study （Jinchang Cohort） to directly evaluate metal exposure levels. Fifteen metals, namely As, Ba, Be, Cd, Cs, Cr, Co, Cu, Pb, Mn, Ni, Se, TI, U, and Zn, were detected by inductively coupled plasma quadruple mass spectrometry. The results showed that median creatinine adjustment and geometric mean urinary metal levels were higher in the heavy metal-exposed group, except Se and Zn, than other reported general or occupational populations. Further studies should address the effects of heavy metals on human health.

Protective effect and mechanism of ginsenoside Rg1 on H2O2 induced hippocampal neurons aging due to down-regulate NOX2 mediated NLRP1 inflammasome activation in vitro

OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1(Rg1) on H_2O_2-induced hippocampal neurons aging in vitro.METHODS The primary culture hippo.campal neurons(7 d) were randomly placed into six groups:normal control group,H_2O_2(200 μM) treat.ment group,and H_2O_2+Rg1(1,5 and 10μM) groups.The neurons were with Rg1(1,5 and 10 μmol·L^(-1))for 6 h.H_2O_2(200 μmol · L-1) was added to the medium and incubate for 18 h.The Dihydroethidium(DHE) staining was performed for ROS production assessment.The LDH release and Hoechst 33258 were performed to examine the neuronal damage and apoptosis.The immunoblot was used to deter.mine the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons.The ELISA was performed to detect the levels of IL-1β and IL-18 released in the supernatant in hippocampal neurons.RESULTS Rg1(5 and 10 μmol·L^(-1)) significantly reduced the ROS production,attenuated H_2O_2-induced neuronal damage and apoptosis(P<0.05,P<0.01).The immunoblot results showed that Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons(P<0.05,P<0.01).Additionally,Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased IL-1β and IL-18 release in the supernatant.CONCLUSION The protective effect of Rg1 in H_2O_2-induced hippocampal neurons aging may be due to inhibit NOX2-NLRP1 activation.

Exome analysis for Cronkhite-Canada syndrome: A case report

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare,non-genetic disorder characterized by multiple gastrointestinal polyps,and ectodermal lesions such as alopecia,fingernail atrophy,and skin mucosal pigmentation.Unfortunately,the pathogenesis of CCS is currently unknown.CASE SUMMARY Here,we describe the case of an elderly female with diarrhea,fatigue,and hair loss,who experienced abdominal pain for over half a year and was found to have multiple gastrointestinal polyps.She was diagnosed with CCS and was treated with albumin supplementation and prednisone,and her electrolyte imbalance was corrected.Following treatment,her symptoms significantly improved.To elucidate the role of potential genetic events in the pathogenesis of CCS,we performed exome sequencing using an extract of her colorectal adenoma.CONCLUSION Our data revealed multiple somatic mutations and copy number variations.Our findings provide a novel insight into the potential mechanisms of CCS etiology.

Nischarin-siRNA delivered by polyethyleniminealginate nanoparticles accelerates motor function recovery after spinal cord injury

A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2 a cells and primary cortical neurons.In recent years,more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury.We proposed that small interfering RNA targeting nischarin（Nis-si RNA） delivered by polyethyleneimine-alginate（PEIALG） nanoparticles promoted motor function recovery in rats with spinal cord injury.Direct microinjection of 5 μL PEI-ALG/Nis-si RNA into the spinal cord lesion area of spinal cord injury rats was performed.From day 7 after surgery,Basso,Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-si RNA group compared with the spinal cord injury group and PEI-ALG/Control-si RNA group.On day 21 after injection,hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-si RNA group.Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-si RNA group.These findings suggest that a complex of PEI-ALG nanoparticles and Nis-si RNA effectively suppresses nischarin expression,induces expression of growth-associated protein-43,and accelerates motor function recovery after spinal cord injury.

Significance of the Expression of Rho-GDP Dissociation Inhibitor β,γ in Lung Squamous Cell Carcinoma and Adenocarcinoma

Objective： To study the expression of Rho-GDP dissociation inhibitor β,γ （Rho-GDIβ, Rho-GDIγ） in lung squamous cell carcinoma and adenocarcinoma and its relationship with the expression of RhoC （Ras homologus oncogenes C） and clinicopathologic parameters. Methods： Western blot assay was employed for Rho-GDIβ, Rho-GDIγand RhoC in lung squamous cell carcinoma and adenocarcinoma and non-neoplastic lung tissues of 37 cases with fresh specimens. Results： The study showed that Rho-GDIβ, Rho-GDIγ and RhoC were expressed in lung cancer and non-neoplastic lung tissues, the level in lung cancer tissue was much higher than that in non-neoplastic tissues （P〈0.001）. In lung cancer, the expression of Rho-GDIβwas much higher in patients with lymph node metastasis （P=0.021）, and the expression of Rho-GDIγ was much higher in poorly differentiated tumor than in well-differentiated and moderately differentiated tumor, but both of them were not correlated with other clinicopathologic parameters. The expressions of Rho-GDIβ and Rho-GDIγ were not correlated with the expression of RhoC. Conclusion： In lung cancer, Rho-GDIβand Rho-GDIγ may play a role in the tumorigenesis, Rho-GDIβ may promote metastasis, and Rho-GDIγ may have some relationship with differentiation.

Brain protection of AC in PTZ-induced epileptic rats

Objective:To investigate the neuroprotective effect and mechanism of Acteoside(AC)on brain injury in epileptic rats.Methods:30 Sprague-Dawlay rats(SPF grade,healthy males,about 200g)were randomly divided into epilepsy group,AC group and blank control group.The epileptic group and the AC group were given 28 days of intraperitoneal injection of pentaerythritazine(PTZ),and the remaining groups were given normal saline injection.The changes of electroencephalogram(EEG),learning and memory ability,pathological changes of brain tissue,superoxide dismutase(SOD)and malondialdehyde(MDA)were observed in all rats.Results:Compared with the epilepsy group,the AC group showed significantly reduced degeneration and necrosis of nerve cells in brain tissue,significantly improved learning and memory ability,and the EEG was dominated by wavelet and slow wave,replacing the typical spike and spike waves.SOD increased and MDA decreased in oxygen radical(P<0.05).Conclusions:Epilepsy are closely related to Oxidative stress.AC can play a protective role in the brain by improving EEG,learning and memory ability,regulating changes in SOD and MDA content,and inhibiting the generation of oxygen free radicals.

Brugada syndrome associated with out-of-hospital cardiac arrest: A case report

BACKGROUND Brugada syndrome(BrS)is an inherited disease characterized by an electrocardiogram(ECG)with a coved-type ST-segment elevation in the right precordial leads(V1-V3),which predisposes to sudden cardiac death(SCD)due to polymorphic ventricular tachycardia or ventricular fibrillation in the absence of structural heart disease.We report the case of a 29-year-old man with out-ofhospital cardiac arrest.BrS is associated with a high incidence of SCD in adults,and increasing the awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving.CASE SUMMARY A 29-year-old man suffered from out-of-hospital cardiac arrest,and after defibrillation,his ECG demonstrated a coved-type elevated ST segment in V1 and V2.These findings were compatible with type 1 Brugada pattern,and ECG of his brother showed a type 2 Brugada pattern.The diagnosis was BrS,NYHF IV,multiple organ dysfunction syndrome,sepsis,and hypoxic ischemic encephalopathy.The patient had no arrhythmia episodes after discharge throughout a follow-up period of 36 mo.CONCLUSION Increasing awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving.

3D Reconstruction of the medullary tubular-vascular relationship in adult mouse kidneys

A close tubular vascular relationship in renal medulla is not only the structural basis for urine concentration,but is also the sensitive position for acute and chronic kidney injury.Therefore,a comprehensive understanding of spatial architecture in medulla is important for nephrologist.Serial sections were obtained from three mouse kidneys and double immunofluorescent stained for CD34 and for either AQP-1 or AQP-2.Using custom:made softwares,525 tubules and 333 vessels were traced,and ultra-structurally analyzed with EM.From corticomedullary boundary to inner medulla,descending and ascending vasa recta(DVR,AVR)closely accompanied with each and ran in the center of vascular bundle(VB).

Signal transduction in the gastrointestinal smooth muscle

平滑肌是胃肠运动的基础,其收缩和舒张涉及电-机械偶联和药物-机械偶联。其中有钙离子和其他信号分子的参与。本文通过电生理特性,钙和钙动员,收缩装置和途径,信号转导途径和交叉对话来总结信号转导在胃肠平滑肌中的作用。

Expression of yeast silencing information regulator 2 in secondary injury of intracerebral hemorrhage

Objective:to investigate the expression of yeast silencing information regulator 2(Sirt2)in the secondary injury of intracerebral hemorrhage(ICH).Methods:twelve Sprague Dawley(SD)rats were randomly divided into a sham group and an ICH group,with six rats in each group.A rat model of ICH was established by injecting collagenase type IV into the right striatum of the rats.The expression of Sirt2 was measured by Western blot and immunohistochemistry after ICH.Result:the behavioral score of the ICH rats was the lowest at 48 h after the operation;therefore the rats at 48 h after surgery were selected as the model rats.The expression of Sirt2 was significantly higher in the striatal tissue of the ICH rats compared with the sham group(P<0.05).Conclusion:the expression of Sirt2 around hematoma in ICH rats decreases,and Sirt2 is expected to become a new target for ICH treatment.

How is artificial intelligence applied in solid tumor imaging?

How is artificial intelligence(AI)applied in solid tumor imaging?What is the essential value of AI for tumor precision diagnosis and can it wholly replace the human beings?Some opinions in this letter should be considered.

Brain Pathology in COVID-19:Clinical Manifestations and Potential Mechanisms

Neurological manifestations of coronavirus disease 2019(COVID-19)are less noticeable than the respiratory symptoms,but they may be associated with disability and mortality in COVID-19.Even though Omicron caused less severe disease than Delta,the incidence of neurological manifestations is similar.More than 30%of patients experienced“brain fog”,delirium,stroke,and cognitive impairment,and over half of these patients presented abnormal neuroimaging outcomes.In this review,we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza infection.We also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 invasion.In addition,we discuss direct damage and other pathological conditions caused by SARS-CoV-2,such as an aberrant interferon response,cytokine storm,lymphopenia,and hypercoagulation,to provide treatment ideas.This review may offer new insights into preventing or treating brain damage in COVID-19.