IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.

BACKGROUND AND AIMS: There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS: From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS: A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS: ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Investigation of Factors Influencing the Fear of Cancer Recurrence in Breast Cancer Patients Using Structural Equation Modeling: A Cross-Sectional Study.

Objective: This study aimed to investigate the fear of cancer recurrence (FCR) in breast cancer patients and develop a structural equation model of influencing factors to help formulate clinical intervention strategies. Methods: A convenience sample of 325 patients was surveyed using a general and disease-related data questionnaire, which combined the Fear of Progression Questionnaire-Short Form, Mishel Uncertainty in Illness Scale, Perceived Social Support Scale, and Medical Coping Modes Questionnaire. Results: The total score of FCR in breast cancer patients was 35.06 ± 10.83, and 53.8% of patients reached the clinical level. The structural equation model demonstrated that illness uncertainty had a direct positive impact on FCR (ß = 0.275, p < 0.05), and it could have an indirect impact through social support and resignation coping methods (ß = 0.254, p < 0.05). Conclusion: The fear of cancer recurrence in breast cancer patients needs further understanding. Medical staff can reduce or buffer FCR in breast cancer patients by strengthening positive influences, such as social support, or weakening negative influences, such as illness uncertainty and resignation coping.

Research Progress on the Application of Human Oral Microbiome in Forensic Individual Identification.

The oral cavity is the second largest microbial bank in humans after the intestinal canal, colonizing a large number of microorganisms including viruses, bacteria, archaea, fungi and protozoa. The great number of microbial cells, good DNA stability, and individual has a unique microbial community, these characteristics make the human microbiome expected to become a new biomarker for forensic individual identification. This article describes the characteristics of human oral microorganisms and microbial molecular markers in detail, analyzes the potential application value of microorganisms in forensic individual identification, and reviews the research progress of human oral microorganisms in forensic individual identification.

Association between psychological capital and spiritual care competencies of clinical nurses: A multicentre cross-sectional study.

AIMS: To investigate the status of spiritual care competencies among clinical nurses and their relationships with psychological capital. BACKGROUND: Limited knowledge is about the influence of positive personal characteristics on nurses' spiritual care competencies. METHODS: A multicentre cross-sectional study. A total of 1717 nurses were recruited from nine separate Chinese hospitals. Online questionnaires were delivered through a local nursing association to assess socio-demographics, spiritual care competencies and psychological capital of nurses. RESULTS: Nurses had mild-to-moderate levels of spiritual care competencies and moderate levels of psychological capital. Psychological capital and its two metrics (self-efficacy and hope), spiritual care education, professional qualification and shift work were the main predictors of spiritual care competencies (each p < .05). CONCLUSION: The findings of the study show a positive relationship between psychological capital and spiritual care competencies of clinical nurses. Strengthening nurses' psychological capital could improve their spiritual care competencies. IMPLICATIONS FOR NURSING MANAGERS: Nurse managers and hospital administrators should better understand the value of psychological capital for nurses' capacity development. Effective interventions need to be implemented separately or combined with spiritual care education programmes to improve nurses' psychological capital and spiritual care competencies.

Curcumin attenuates cognitive impairment by enhancing autophagy in chemotherapy.

Cisplatin, a commonly used chemotherapy drug, can increase the survival rate of cancer patients. However, it often causes various side effects, including neuronal deficit-induced cognitive impairment. Considering that curcumin is effective in neuronal protection, the action of curcumin on cognitive improvement was evaluated in cisplatin-treated C57BL/6 mice in the present study. Our results first showed that curcumin restored impaired cognitive behaviors. Consistent with this, neurogenesis and synaptogenesis were improved by curcumin. In addition, cisplatin-induced dysfunction of apoptosis-related proteins was partly reversed by curcumin. Moreover, cisplatin-induced autophagy was enhanced by curcumin. Our results also indicated that cisplatin induced autophagy through the endoplasmic reticulum (ER) stress-mediated ATF4-Akt-mTOR signaling pathway. Curcumin activated AMPK-JNK signaling, which mediated both mTOR inhibition and Bcl-2 upregulation and in turn enhanced autophagy and suppressed apoptosis, respectively. In contrast, pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) completely abolished the effects of curcumin on cognitive improvement and improved neurogenesis, synaptogenesis and autophagy. Our results show that cognitive improvement induced by curcumin during chemotherapy is mediated by the enhancement of hippocampal autophagy.

PIFA-Mediated Dearomatizative Spirocyclization of Phenolic Biarylic Ketones via Oxidation and C-C Bond Cleavage.

The dearomatizing spirocyclization of phenolic biarylic ketones using PhI(OCOCF3)2 as oxidant is presented. The reaction affords various cyclohexadienones through C-C bond cleavage under mild conditions. Mechanistic investigations reveal that an exocyclic enol ether acts as the key intermediate in the transformation.

Ursolic acid potentiated oxaliplatin to induce apoptosis in colorectal cancer RKO cells.

Ursolic acid (UA) is found in multiple anticancer herbs and has shown anticancer effects in colorectal cancer (CRC) cells. The present study aimed to observe the effects of a combination of UA and oxaliplatin (Oxa), a frequently used chemotherapeutic drug in CRC, on human CRC RKO cells. The results showed that UA and Oxa synergistically inhibited the proliferation of RKO cells. A combination of UA and Oxa induced apoptosis in RKO cells and increased the activities of caspase-3, caspase-8, and caspase-9. Z-VAD-FMK, a caspase inhibitor, significantly antagonized UA- and Oxa-activated caspase-3, caspase-8, and caspase-9 and induced apoptosis. In addition, UA and Oxa downregulated the expression of X-linked inhibitor of apoptosis (XIAP) and Survivin in RKO cells. These observations suggested that a combination of UA and Oxa elicited synergistically anticancer effects in RKO cells and provided new evidence for potential application of UA and Oxa for CRC treatment.

[Association of rs4638289 and rs7131332 polymorphisms of the serum amyloid A1 gene with Kawasaki disease].

OBJECTIVE: To study the association of the polymorphisms of the serum amyloid A1 (SAA1) gene at rs4638289 and rs7131332 loci with Kawasaki disease (KD) and its complication coronary artery lesion (CAL) in children. METHODS: A total of 105 Han children with KD who were hospitalized and treated from 2013 to 2017 were enrolled as the KD group. A total of 100 Han children who underwent physical examination were enrolled as the control group. According to the presence or absence of CAL, the KD group was further divided into a CAL group with 23 children and a non-CAL (NCAL) group with 82 children. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the polymorphisms of the SAA1 gene at rs4638289 and rs7131332 loci. RESUKTS: For the locus rs4638289 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AT, and TT and the allele frequencies of A and T (P>0.05). But there were significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AT, and TT (P=0.016), while there were no significant differences in the allele frequencies of A and T (P>0.05). AT genotype was a protective factor against CAL (OR=0.276, 95%CI: 0.099-0.772, P=0.011). For the locus rs7131332 of the SAA1 gene, there were no significant differences between the KD and control groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05). There were also no significant differences between the CAL and NCAL groups in the genotype frequencies of AA, AG, and GG and the allele frequencies of A and G (P>0.05). CONCLUSIONS: Polymorphisms of the SAA1 gene at loci rs4638289 and rs7131332 are not associated with the onset of KD, while the polymorphism at the locus rs4638289 is associated with CAL in KD patients. KD patients with genotype AT may have a reduced risk of CAL.

[Association of T-wave amplitude on electrocardiogram with left ventricular ejection fraction in children with dilated cardiomyopathy].

OBJECTIVE: To study the association of T-wave amplitude on electrocardiogram (ECG) with left ventricular ejection fraction (LVEF) in children with dilated cardiomyopathy. METHODS: A retrospective analysis was performed for the clinical data of 44 children who were diagnosed with dilated cardiomyopathy from May 2009 to June 2018. According to LVEF, they were divided into two groups: LVEF ≥50% group (n=26) and LVEF <50% group (n=18). After treatment, 25 children were followed up for 3-42 months (mean 14±9 months). The Guangdong Zhongshan SR-1000A ECG Automatic Analyzer was used to obtain the 12-lead body surface ECG results in the supine position. T-wave amplitude on ECG was evaluated by software and manual measurement. RESULTS: Compared with the LVEF ≥50% group, the LVEF <50% group had a significant reduction in the T-wave amplitude in leads II, V4, V5 and V6 (P<0.05). The increased-LVEF group (an increase in LVEF > 5% after treatment) had a significant increase in the T-wave amplitude in leads aVR, V5, and V6 after treatment (P<0.05), while the unchanged-LVEF group (an increase in LVEF ≤ 5% after treatment) had a significant reduction in the T-wave amplitude in lead aVR after treatment (P<0.05). The receiver operating characteristic curve analysis showed that the T-wave amplitude in leads II, V4, V5 and V6 had a certain value in predicting LVEF <50% in children with dilated cardiomyopathy (P<0.05). A combination of T-wave amplitude of ≤0.20 mV in lead II, ≤0.40 mV in lead V4, and ≤0.30 mV in leads V5 and V6 had a sensitivity of 88.2% and specificity of 76.0% in the predication of LVEF <50% in children with dilated cardiomyopathy. CONCLUSIONS: T-wave amplitude on ECG can be used as the indexes for the evaluation of the left ventricular systolic function in children with dilated cardiomyopathy.

Abnormalities in acute salivary biochemical characteristic responses to gustatory stimulation with citric acid in chronic non-atrophic gastritis.

BACKGROUND AND AIM: Salivary characteristics are altered in gastrointestinal diseases and related to oral taste disorder. However, specific salivary biochemical characteristics and their relationships with oral taste disturbances in chronic non-atrophy gastritis (CNAG) remain uncertain. METHODS: Seventy patients with CNAG and 70 subjects in healthy control group (HCG) were enrolled in our study. The levels of salivary flow rate (SFR), pH, salivary α-amylase (sAA) activity, total protein density (TPD), chloride concentration, and calcium concentration were determined before and after citric acid stimulation and compared between CNAG with and without oral taste disturbances. RESULTS: Average body mass index (BMI) of CNAG (17.75 ± 2.08) was lower than that of HCG (21.96 ± 1.72, P < 0.01). Compared with HCG, CNAG showed increased TPD and calcium concentration but decreased SFR both before and after acid stimulation (P < 0.01), as well as reduced sAA and salivary chloride responses to acid stimulation (P < 0.01). Compared with CNAG with normal BMI (24.29%, 17/70), sAA activity response to acid stimulation was reduced in those with low BMI (75.71%, 53/70, P < 0.05). Under resting condition, CNAG with dry mouth (55.71%, 39/70) showed increased SFR and decreased TPD (P < 0.05), as compared with CNAG without dry mouth (44.29%, 31/70). Compared with CNAG without bitter taste (57.14%, 40/70), pH was decreased in those with bitter taste (42.86%, 30/70) under both resting and stimulated conditions (P < 0.05). CONCLUSION: Decreased sAA activity may reflect malnutrition state and be one potential marker of poor digestion, decreased salivary pH may contribute to bitter taste perception, and reduced TPD might be a cause of dry mouth in CNAG.

[Change in P wave on electrocardiogram and its diagnostic value in children and adolescents with cardioinhibitory vasovagal syncope].

OBJECTIVE: To study the change in P wave on electrocardiogram and its diagnostic value in children and adolescents with cardioinhibitory vasovagal syncope (VVS-CI). METHODS: A total of 43 children and adolescents who were diagnosed with VVS-CI were enrolled as the VVS-CI group, and 43 healthy children and adolescents were enrolled as the control group. P wave duration and P wave voltage were measured by 12-lead electrocardiography in a basal state, and the changes were analyzed. RESULTS: Compared with the control group, the VVS-CI group had a significantly lower heart rate (P<0.05) and significantly longer P wave duration (Pwd), P wave maximum duration (Pmax), and corrected P wave maximum duration (Pcmax), as well as significantly higher P wave dispersion (Pd) and corrected P wave dispersion (Pcd) (P<0.05). Pwd, Pmax, Pd, Pcmax and Pcd had a certain diagnostic value in children and adolescents with VVS-CI (P<0.05): Pwd had a sensitivity of 69.77% and a specificity of 83.72% at the optimal cut-off value of 78.49 ms; Pmax had a sensitivity of 76.74% and a specificity of 90.70% at the optimal cut-off value of 93.39 ms; Pd had a sensitivity of 95.35% and a specificity of 69.77% at the optimal cut-off value of 27.42 ms; Pcmax had a sensitivity of 46.51% and a specificity of 88.37% at the optimal cut-off value of 120.90 ms; Pcd had a sensitivity of 83.72% and a specificity of 72.09% at the optimal cut-off value of 36.37 ms. CONCLUSIONS: Children and adolescents with VVS-CI have significantly increased Pwd, Pmax, Pd, Pcmax, and Pcd, which may indicate abnormal atrial electrical activity. The cut-off value of P wave has a certain diagnostic value in VVS-CI.

Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma.

Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed.

Arabidopsis thaliana†CML25 mediates the Ca(2+) regulation of K(+) transmembrane trafficking during pollen germination and tube elongation.

The concentration alteration of cytosolic-free calcium ([Ca(2+) ]cyt ) is a well-known secondary messenger in plants and plays important roles during pollen grain germination and tube elongation. Here we demonstrate that CML25, a member of calmodulin-like proteins, has Ca(2+) -binding activity and plays a role in pollen grain germination, tube elongation and seed setting. CML25 transcript was abundant in mature pollen grains and pollen tubes, and its product CML25 protein was primarily directed to the cytoplasm. Two independent CML25 loss-of-function T-DNA insertion mutants suffered a major reduction in both the rate of pollen germination and the elongation of the pollen tube. Also, pollen grains of cml25 mutants were less sensitive to the external K(+) and Ca(2+) concentration than wild-type pollen. The disruption of CML25 increased the [Ca(2+) ]cyt in both the pollen grain and the pollen tube, which in turn impaired the Ca(2+) -dependent inhibition of whole-cell inward K(+) currents in protoplasts prepared from these materials (pollen grain and pollen tube). Complementation of cml25-1 mutant resulted in the recovery of wild-type phenotype. Our findings indicate that CML25 is an important transducer in the Ca(2+) -mediated regulation of K(+) influx during pollen germination and tube elongation.

Arabidopsis thaliana calmodulin-like protein CML24 regulates pollen tube growth by modulating the actin cytoskeleton and controlling the cytosolic Ca(2+) concentration.

Cytosolic free calcium ([Ca(2+)]cyt), which is essential during pollen germination and pollen tube growth, can be sensed by calmodulin-like proteins (CMLs). The Arabidopsis thaliana genome encodes over 50 CMLs, the physiological role(s) of most of which are unknown. Here we show that the gene AtCML24 acts as a regulator of pollen germination and pollen tube extension, since the pollen produced by loss-of-function mutants germinated less rapidly than that of wild-type (WT) plants, the rate of pollen tube extension was slower, and the final length of the pollen tube was shorter. The [Ca(2+)]cyt within germinated pollen and extending pollen tubes produced by the cml24 mutant were higher than their equivalents in WT plants, and pollen tube extension was less sensitive to changes in external [K(+)] and [Ca(2+)]. The pollen and pollen tubes produced by cml24 mutants were characterized by a disorganized actin cytoskeleton and lowered sensitivity to the action of latrunculin B. The observations support an interaction between CML24 and [Ca(2+)]cyt and an involvement of CML24 in actin organization, thereby affecting pollen germination and pollen tube elongation.

Four-component bicyclization approaches to skeletally diverse pyrazolo[3,4-b]pyridine derivatives.

A novel four-component bicyclization strategy has been established, allowing a flexible and practical approach to 37 examples of multicyclic pyrazolo[3,4-b]pyridines from low-cost and readily accessible arylglyoxals, pyrazol-5-amines, aromatic amines, 4-hydroxy-6-methyl-2H-pyran-2-one, and cyclohexane-1,3-diones. The polysubstituted cyclopenta[d]pyrazolo[3,4-b]pyridines were stereoselectively synthesized through a microwave-assisted special [3+2+1]/[3+2] bicyclization with good control of the spatial configuration of exocyclic double bonds. The novel [3+2+1]/[2+2+1] bicyclization resulted in 17 examples of unreported pyrazolo[3,4-b]pyrrolo[4,3,2-de]quinolones. Reasonable mechanisms for forming two new types of multicyclic pyrazolo[3,4-b]pyridines are also proposed.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Cloning, subcellular localization and expression analysis of squalene epoxidase gene BsSE1 from Bletilla striata.

Squalene epoxidase catalyzes the oxidation of squalene to 2,3-oxo-squalene (BsSE1), and is the key rate limiting enzyme in the synthesis of triterpenoids and sterols in plants. This study focused on the basic aspects of BsSE1 including the sequence information, sub-cellular localization expression patterns of BsSE1. Using to the sequence information of Bletilla striata transcriptome, the full-length CDS of BsSE1 gene was amplified. The physicochemical properties and structural characteristics of BsSE1 protein were analyzed by bioinformatics analysis software, and vector was constructed to analyze the protein locations and expression patterns. The results showed that the CDS of BsSE1 gene was 1542 bp, encoding 513 amino acids. BsSE1 protein is a hydrophobic protein with two transmembrane domains but no signal peptides. It is localied in the endoplasmic reticulum membrane and belongs to the typical squalene epoxidase gene. BsSE1 has the closest genetic relationship with SE protein of Dendrobium officinale and Phalaenopsis equestris. The expression level of BsSE1 was higher in pseudobulblet of Bletilla striata seedlings, followed by roots, and lower in seedling stems. After SA induction, the expression of BsSE1 in Bletilla striata showed significant changes, increased first, then decreased, finally increase again. The results provide a basis for further study of this gene family in plants.

Research Models in Dentine Development and Regeneration.

Dentine is a major component of teeth and is responsible for many of their functions, such as mastication and neural sensation/transduction. Over the past decades, numerous studies have focused on dentine development and regeneration using a variety of research models, including in vivo, ex vivo and in vitro models. In vivo animal models play a crucial role in the exploration of biochemical factors that are involved in dentine development, whereas ex vivo and in vitro models contribute mainly to the identification of biophysical factors in dentine regeneration, of which mechanical force is most critical. In the present review, research models involved in studies related to dentine development and regeneration were screened from publications released in recent years and summarised comprehensively, particularly in vivo animal models including prokaryotic microinjection, Cre/LoxP, CRISPR/Cas9, ZFN and TALEN, and scaffold-based in vitro and ex vivo models. The latter were further divided by the interactive forces. Summarising these research models will not only benefit the development of future dentine-related studies but also provide hints regarding the evolution of novel dentine regeneration strategies.