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BACKGROUND@#Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.@*METHODS@#In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4 ), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.@*RESULTS@#We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.@*CONCLUSION@#We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.
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Animals , Humans , Mice , Acute-On-Chronic Liver Failure/pathology , ATP-Dependent Proteases/metabolism , Gluconeogenesis , Hepatocytes/pathology , Liver/metabolism , Mitochondrial Proteins/metabolism , Protease La/metabolismABSTRACT
Positron emission tomography (PET) now plays an important role in the research and development (R&D) of central nervous system (CNS) drugs. PET could characterize the biodistribution, pharmacokinetics, and receptor binding of CNS drugs quantitatively. The present review summarized the quantitative methods of PET used in the pharmacokinetics and receptor occupancy analysis of CNS drugs. Moreover, the present review listed various applications of PET supporting R&D of CNS drugs, which could provide a new direction for the R&D of CNS drugs.
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Objective@#To evaluate the immunity and influencing factors of diphtheria among preschool children in Shenzhen,to provide reference for effective monitoring of diphtheria IgG antibody level in preschool children.@*Methods@#Serum samples were collected from 296 preschool children aged 4-6 who were recruited in Shenzhen. The diphtheria antibody titer in serum was determined by enzyme linked immunosorbent assay, and the effect of different immumuzation schedule including types of vaccine and vaccination timing, on the geometric mean concentration (GMC) of diphtheria IgG antibody and antibody positive rate were analyzed.@*Results@#The GMC of diphtheria IgG antibody was 0.71 IU/mL, and the positive conversion rate was 33.1%. There were significant differences in antibody GMC and antibody positive conversion rate of diphtheria in different age groups( F/χ 2=11.77, 27.45, P < 0.01 ). The GMC and antibody positive conversion rate showed significant differences by diphtheria antibodies, vaccine types and end dose vaccination intervals( F=49.53, 12.95，11.61, P <0.01). There were statistically significant differences in the positive conversion rate of diphtheria antibodies in children with different types of diphtheria antibodies, vaccine types of diphtheria antibodies, and diphtheria antibodies at the time interval of final vaccination (Fisher exact probability method, P <0.01).@*Conclusion@#The overall positive conversion rate of diphtheria antibody in preschool children in Shenzhen is high. Timely completion of full diphtheria vaccination can improve the antibody level and plays a better role in protecting preschool children.
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Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.
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Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.
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Objective To stud)' the nerve repair effect of olanzapine on schizophrenia model rats through its effect on cyclic AMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/receptor tyrosine kinase receptors B (TrkB) pathway. Methods Total 60 rats were divided into control group, model group, olanzapine low, middle and high dose group. The rats in the model group, olanzapine low, middle and high dose groups were injected intraperitoneally with MK-801[0. 2 mg/(kg-d) ], while the control injected with the same amount of normal saline. The low, middle and high dose olanzapine groups were perfused with olanzapine solution of 0. 5 mg/(kg-d),1. 0 mg/(kg-d) and 1. 5 mg/(kg-d) respectively. The behavior of rats was scored according to ataxia and stereotyped behavior standards, cognitive function and learning ability were evaluated by Moms water maze test, serum tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels were detected by ELISA method, hippocampal histopathology was observed under microscope, and apoptosis and expression of CREB/BDNF/TrkB pathway related proteins in hippocampus were detected. Results Compared with the control group, the ataxia, the score of stereotyped behavior, the expression of TNF-a, IL-6 and the rate of apoptosis in the model group increased significantly (P < 0 . 01). Compared with the control group, the number of crossing the platform, the time of staying in the target quadrant and the relative expression of CREB, p-CREB, p-TrkB, TrkB and BDNF protein in the model group decreased significantly (P<0. 01), and those in the low and middle dose olanzapine groups decreased significantly (P < 0 . 05). Compared with the model group, the times of crossing the platform and the stay time in the target quadrant increased significantly in the low and middle dose olanzapine groups (P< 0. 05). In the model group and the low dose olanzapine group, the hippocampal cells were swollen obviously, the nucleus was broken and divided, pyknosis, and the tissue aiTangement was disorderly, while the phenomenon of fragmentation and nuclear pyknosis was rarely seen in the middle and high dose olanzapine groups. Conclusion The nerve repair mechanism of olanzapine on schizophrenic model rats is related to improving cognitive impainnent, protecting hippocampal neurons and activating the expression of CREB/BDNF/TrkB signal pathway in rats.
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Objective To improve the fixation method of the transmission electron microscope for better morphological preservation of mitochondria and lipid droplets in mouse brown adipose tissue. Methods The fixation method for mouse brown adipose tissue was optimized, mainly including an increased concentration of paraformaldehyde from 2% to 4% in the pre-fixative, employment of transcardial perfusion followed by immersion fixation in pre-fixation, and using imidazole-buffered osmium tetroxide as the post-fixative. The ultrastructures of brown adipocytes prepared by the improved method were observed and compared with those of a known standard protocol (3 mice in each group). The improved method was further validated in the quantitative analysis of mitochondrial cristae density and lipid droplets. Results The mitochondrial cristae and membrane structure of other organelles of brown adipocytes were better preserved using the optimized method compared with those of the standard method. Lipid droplets were presented as round structures with high electron density instead of vacuolated appearances. Using this method, we observed that the density of mitochondrial cristae and the content of lipid droplets increased in brown adipocytes after cold adaptation. Conclusion The optimized method can better preserve the ultrastructure of organelles in brown adipocytes, especially mitochondria and lipid droplets, and ma)' be applicable for studying the ultrastructures remodeling of brown adipose tissue under different physiological or pathological conditions.
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This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.
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Humans , Rats , Female , Animals , Estrogen Receptor alpha , Oxytocin , Dysmenorrhea/metabolism , Cyclooxygenase 2 , Dinoprostone , RNA, Messenger/metabolism , DinoprostABSTRACT
Irritable bowel syndrome (IBS) is a common refractory disease. Chinese medicine (CM) has remarkable efficacy and advantages on the treatment of IBS. This review summarized the articles focusing on the treatment of IBS with CM to sum up the latest treatment methods for IBS and the underlying mechanisms. Literature analysis showed that prescriptions, acupuncture, and moxibustion are the primary methods of CM treatment for IBS. The potential mechanism centers on the regulation of the enteric nervous system, the alleviation of visceral hypersensitivity, the stability of intestinal flora, and the regulation of the immune system.
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Humans , Irritable Bowel Syndrome/therapy , Medicine, Chinese Traditional , Acupuncture Therapy/methods , MoxibustionABSTRACT
ObjectiveTo evaluate the current situation of human resource allocation in district and county centers for disease control and prevention （CDCs） in Kashgar ， identify existing problems and influencing factors， and to provide scientific evidence for optimizing the human resource allocation. MethodsA survey was conducted among all CDCs in Kashgar in February 2022. The questionnaire included the institutional and individual questions. ResultsThe overall staff size approved for the CDCs in Kashgar was 604， with a staffing rate of 76.17%， among which the staffing rates in 5 county CDCs were less than 60%. Currently， there were a total of 524 approved staff members in all CDCs， resulting in a vacancy rate of 13.25%. In the district CDC， 85 staff members were on duty， while the median of staff on duty was 34 in each county CDC. The staff in the district CDC was ageing， of which those aged over 45 accounted for 67.06%. The staff in the county CDCs was generally young， of which those aged less than 35 accounted for 54.22%. Moreover， the proportion of staff with bachelor’s degree or above in the district and county CDCs was 31.76% and 24.95%， respectively. The proportion of staff without professional title was 32.94% and 48.03%， respectively. In contrast， the proportion of those with middle and senior professional title was 57.89% and 22.02%， respectively. In addition， in recent 3 years， 24 staff members resigned in the CDCs， all of whom had professional titles. ConclusionHuman resources are insufficient in CDCs in Kashgar. Furthermore， staff structure is unreasonable， with a serious loss of human resources. In particular， the district CDC needs to optimize the allocation of human resources.
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Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.
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Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.
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OBJECTIVE@#To explore the synergic mechanism of ginsenoside Rg1 (Rg1) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs.@*METHODS@#The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+], potassium ions [K+] and calcium ions [Ca2+] levels, and Nav1.5, Kv4.2, and RyR2 genes expressions in each group were examined.@*RESULTS@#For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ via regulating Nav1.5, RyR2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs.@*CONCLUSION@#Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+].
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Animals , Rats , Aconitine/pharmacology , Apoptosis , Cardiotonic Agents/pharmacology , Cardiotoxicity/drug therapy , Cell Survival , Ginsenosides/pharmacologyABSTRACT
Aim To determine the antiviral and anti-inflammatory effects of the recommended prescription for COVID-2019-lung-spleen qi deficiency(4-1)against in vitro infection of SARS-CoV-2 and common coronaviruses.Methods The main chemical substances of 4-1 were analyzed by LC-MS.The toxicity and antiviral effects of of 4-1 were detected by MTT and by CPE assay, respectively.The viral loads in cell supernatant and the expression of inflammatory factors induced by viral infection were determined by qRT-PCR.Results The recommended prescription 4-1 contained 94 chemical compounds, including flavonoids, steroids, sesquiterpenoids, and so on.The range of selection indexes for SARS-CoV-2 and common coronaviruses was 8.44±0.4952.26±2.3.This prescription could inhibit the proliferation of SARS-CoV-2, the expression of ACE2 and S mRNA, and down regulate IL-1α and CCL-5/RANTES at 10, 5, and 2.5 g•L-1 doses.Further, at doses of 20, 10 and 5 g•L-1, it could inhibit the proliferation of three common coronaviruses and suppress the overexpression of IL-6, CXCL-8/IL-8, CXCL-10/IP-10, TNF-α, IFN-α, CCL-2/MCP-1, MIG and CCL-5/RANTES induced by OC43/229E infection.The inhibitory effects were dose-dependent.Conclusions The prescription 4-1 has antiviral and anti-inflammation effects against multiple coronaviruses.This study provides the research basis for the treatment of common respiratory viral infections and emerging infectious diseases such as COVID-19 by using traditional Chinese medicine.
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Objective To establish an artificial intelligence model based on B-mode thyroid ultrasound images to predict central compartment lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC). Methods We retrieved the clinical manifestations and ultrasound images of the tumors in 309 patients with surgical histologically confirmed PTC and treated in the First Medical Center of PLA General Hospital from January to December in 2018.The datasets were split into the training set and the test set.We established a deep learning-based computer-aided model for the diagnosis of CLNM in patients with PTC and then evaluated the diagnosis performance of this model with the test set. Result The accuracy,sensitivity,specificity,and area under receiver operating characteristic curve of our model for predicting CLNM were 80%,76%,83%,and 0.794,respectively. Conclusion Deep learning-based radiomics can be applied in predicting CLNM in patients with PTC and provide a basis for therapeutic regimen selection in clinical practice.
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Humans , Artificial Intelligence , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis , Retrospective Studies , Risk Factors , Thyroid Cancer, Papillary/diagnostic imaging , Thyroid Neoplasms/diagnostic imagingABSTRACT
@#In order to sustain prodigious anabolic needs, tumor cells need metabolic reprogramming that differs from untransformed somatic cells.Besides glucose metabolism in tumor, amino acid metabolism also plays an important role in tumor cell proliferation, migration, and invasion.It is an emerging trend in tumor energy metabolism research.The metabolic pathway of cysteine, a glucose-producing amino acid, involves a variety of enzymes and products, regulating physiological and pathological processes such as oxidative stress, energy metabolism, and autophagy.This article focuses on the exogenous transport and endogenous conversion pathways of cysteine in tumor cells, the various regulatory mechanisms of cysteine metabolism pathways on the occurrence and development of tumors, and the potential therapeutic targets based on cysteine metabolism pathways, which can provide a theoretical basis for clinical use of drugs against tumors.
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Objective:To investigate the expression of long non-coding RNA (lncRNA) BDNF-AS in kidney cancer tissues, and its effect on the proliferation and migration ability of kidney cancer cells and the molecular mechanism.Methods:Real-time reverse quantitative polymerase chain reaction (rRT-PCR) was used to detect the expression levels of BDNF-AS gene in renal cancer tissues, tumor-adjacent tissues of 67 renal cancer patients and normal renal tubular epithelial cells HK-2 and renal cancer cell lines A498, ACHN, OS-RC-2, Caki-1, 786-O in Huangshi Central Hospital of Edong Medical Group from May 2017 to July 2018. The kidney cancer cell line with the lowest expression of BDNF-AS was taken as the research object. Transient transfection with BDNF-AS overexpression plasmid was treated as the experiment group or a plasmid carrying meaningless sequences was treated as the control group. rRT-PCR was used to detect transfection efficiency. After the transfection with Caki-1 for 24 h, methythiazolyl tetrazolium (MTT) method was used to detect the proliferation of cells in both groups, Transwell migration assay was applied to detect the cell migration ability, rRT-PCR was used to detect the expression level of protein tyrosine phosphatase receptor type G (PTPRG) mRNA and Western blot was used to detect the expression level of PI3K-AKT pathway related-proteins.Results:The relative expression level of BDNF-AS in kidney cancer tissues was lower than that in tumor-adjacent tissues (0.96±0.24 vs. 4.62±0.84, t = 41.76, P < 0.01). The relative expression of BDNF-AS in kidney cancer cell lines was lower than that in normal renal tubular epithelial cells HK-2 (all P < 0.05), and the relative expression in Caki-1 cells was the lowest (0.10±0.01). The relative expression of BDNF-AS in the experimental group was higher than that in the control group ( P < 0.01). From the second day of transfection, the proliferation ability of Caki-1 cells in the experimental group was lower than that in the control group (all P < 0.05). The number of Caki-1 migrated cells in the experimental group was lower than that in the control group after migration for 15 h of Caki-1 cells transfected for 24 h [(51±8) vs. (192±25), t = 5.31, P < 0.01]. After 48 h transfection, the relative expression of PTPRG mRNA in Caki-1 cells ( P < 0.01) and protein expression of the experimental group were higher than those of the control group, the expression levels of PI3K-AKT signaling pathway related-proteins p-PI3K, p-AKT, p-Tpl2 in Caki-1 cells of the experimental group were lower than those of the control group. Conclusions:The expression of BDNF-AS is down-regulated in kidney cancer tissues and cell lines. Overexpression of BDNF-AS can inhibit the proliferation and migration ability of kidney cancer Caki-1 cells. The molecular mechanism may be related to the transduction that BDNF-AS promotes PTPRG gene expression and interferes with PI3K-AKT signaling pathway.
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Objective:To study the results of surgical treatment on post-pancreaticoduodenectomy hemorrhage (PPH).Methods:The clinical data of 47 patients who developed PPH after pancreaticduodenectomy treated with surgery at the First Affiliated Hospital of University of Science and Technology of China from January 2012 to December 2020 were retrospectively analyzed. The operative indications, bleeding site, intraoperative treatment and prognosis were analyzed.Results:There were 33 males and 14 females, aged 42 to 81 (mean 60) years. Early hemorrhage occurred in 17 patients and delayed hemorrhage in 30 patients. A total of 35 patients developed intraperitoneal hemorrhage, 7 gastrointestinal hemorrhage and 5 intraperitoneal combined with gastrointestinal hemorrhage. The indications for surgery were hemodynamic instability ( n=31) and other treatment failure ( n=10). In 17 patients (36.2%), hemorrhage was associated with blood vessels. In 14 patients (29.8%), hemorrhage was associated with anastomotic stoma, while in 6 patients (12.8%) with gastrointestinal hemorrhage, the bleeding was non-anastomotic related. Early hemorrhage was mainly vascular related, and the surgical treatment mainly consisted of suture hemostasis at the bleeding site combined with abdominal irrigation and drainage. Delayed hemorrhage was most commonly anastomotic associated, and its management should consider avoiding anastomotic fistula formation after treatment. The operation time of early hemorrhage was significantly shorter than that of delayed hemorrhage [(136.0±37.5) min vs. (191.1±73.8)min, t=-3.289, P<0.05]. The incidence of re-hemorrhage was 23.4% (11 patients) and 9 patients died with a mortality rate of 19.1%. The re-hemorrhage and mortality rates of early-stage bleeding were significantly lower than those of delayed bleeding [5.9%(1/17) vs. 33.3%(10/30), 0 vs. 30.0%(9/30), P<0.05]. Conclusions:Surgical treatment of early hemorrhage had better results than that of delayed bleeding. Patients with anastomotic related hemorrhage were at high-risks of postoperative death after surgery. Recurrent bleeding was the main cause of death.
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Objective:To explore the molecular mechanism of microRNA (miRNA, miR)-1914-3p regulating the expression of ARL4C and affecting the invasion and proliferation of renal cancer cells.Methods:Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of miR-1914-3p in tumor tissues and adjacent tissues of 53 renal cancer patients, 4 types of renal cancer cell lines (ACHN, OS-RC-2, 786-O, A498) and normal proximal renal tubular epithelial cell line (HK-2). The nonsense sequence (NC) and miR-1914-3p mimic were transiently transfected into renal cancer cells with the lowest miR-1914-3p expression by liposome method, namely the NC group and miR-1914-3p group. qRT-PCR was used to detect the expression level of miR-1914-3p in transfected cells. Transwell invasion test and cell counting kit-8 (CCK-8) were used to detect the invasion and proliferation ability of each group of cells. Bioinformatics software and dual luciferase gene report experiment were used to predict and test the targeted regulation mechanism of miR-1914-3p on target genes. qRT-PCR and Western blot was conducted to analyze the target gene expression level in cells of each group.Results:The expression level of miR-1914-3p in renal cancer tissue was significantly lower than that in adjacent tissues ( P<0.01). The expression level of miR-1914-3p in renal cancer cell lines was significantly lower than that in HK-2 cell lines ( P<0.01), and the expression of miR-1914-3p in OS-RC-2 cells was the lowest ( P<0.01). The expression of miR-1914-3p in the NC group and the miR-1914-3p group were (1.04±0.17) and (11.40±0.91), respectively. The expression level of miR-1914-3p in the miR-1914-3p group was significantly increased ( P<0.01), indicating that the transfection was successful. Overexpression of miR-1914-3p can significantly inhibit the invasion ( P<0.01) and proliferation ( P<0.05) of renal cancer OS-RC-2 cells. Dual luciferase gene report experiment indicated that the target gene of miR-1914-3p may be ADP-ribosylation factor-like 4C (ARL4C); miR-1914-3p can significantly inhibit the luciferase activity of wild-type ARL4C-3′UTR ( P<0.01). Overexpression of miR-1914-3p decreased the expression of ARL4C mRNA and protein in OS-RC-2 cells ( P<0.01), and decreased the expression of cell invasion phenotype proteins (Snail, Slug) and cell proliferation phenotype proteins (Mcm2, Mcm7) ( P<0.01). Conclusions:miR-1914-3p is low-expressed in renal cell carcinoma. It inhibits the invasion and proliferation of renal cell carcinoma OS-RC-2 cells through targeted interference with the expression of the oncogene ARL4C, and participates in the occurrence and development of renal cell carcinoma.
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Objective To explore the effect of budesonide suspension for inhalation in the treatment of childhood asthma and its influence on growth and development in 1-2 years. Methods The 68 children with asthma admitted to our hospital from October 2016 to January 2017 were selected. Every patient had acute attacks and received continued medication. 34 patients treated with salbutamol sulfate inhaled aerosol were used as the control group. 34 patients treated with budesonide suspension combined with salbutamol sulfate aerosol were classified as the observation group. The interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), high-sensitivity-C-reactive protein (hs-CRP), maximum respiratory flow, IS maximum expiratory volume, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, wet rales disappearing time, cough disappearing time, and the two year follow-up indicators of growth and development were compared. Results After medication, IL-6, TNF-α, hs-CRP, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, moist rales disappearance time, and cough disappearance time were lower in the observation group(P<0.05). The maximum respiratory flow and IS maximum expiratory volume in the observation group were higher than those in the control group (P<0.05). The GH level, height, and weight obtained from two year follow up in the observation group were lower than those in the control group (P<0.05). Conclusion Budesonide suspension combined with salbutamol sulfate aerosol inhalation therapy can alleviate the inflammatory reaction, improve the lung function and immune function of children, and accelerate the disappearance of clinical symptoms, but it will affect the growth and development of children to a certain extent.