[Correlation between the mutation spectrum of the UGT1A1 gene and clinical phenotype in patients with inherited hyperunconjugated bilirubinemia].

Objective: To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Methods: Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ(2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results: 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (n=10) and TA7/TA7 (n=14) mutations were statistically significant in TBil (t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous (n=9) and isolated (n=15) mutation had no statistical significance in TBil (t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (F=270.992, P<0.001). There was no statistically significant difference (χ(2)=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion: The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.

[Granulomatous disease with liver injury as the main manifestation].

Hepatic granuloma is a kind of disease caused by both infection or non-infection etiologies, and it is found in approximately 2% to 15% of liver biopsies. Some of which could be identified by the pathological morphology. This article reviews the common etiology, pathological manifestations, diagnosis, and differential diagnosis of hepatic granuloma, which is hopeful to improve clinicians' and pathologists' awareness.

Seismic magnitude clustering is prevalent in field and laboratory catalogs.

Clustering of earthquake magnitudes is still actively debated, compared to well-established spatial and temporal clustering. Magnitude clustering is not currently implemented in earthquake forecasting but would be important if larger magnitude events are more likely to be followed by similar sized events. Here we show statistically significant magnitude clustering present in many different field and laboratory catalogs at a wide range of spatial scales (mm to 1000 km). It is universal in field catalogs across fault types and tectonic/induced settings, while laboratory results are unaffected by loading protocol or rock types and show temporal stability. The absence of clustering can be imposed by a global tensile stress, although clustering still occurs when isolating to triggered event pairs or spatial patches where shear stress dominates. Magnitude clustering is most prominent at short time and distance scales and modeling indicates >20% repeating magnitudes in some cases, implying it can help to narrow physical mechanisms for seismogenesis.

Single-Cell Transcriptomic Atlas of Gingival Mucosa in Type 2 Diabetes.

The oral gingival barrier is a constantly stimulated and dynamic environment where homeostasis is often disrupted, resulting in inflammatory periodontal diseases. Type 2 diabetes (T2D) has been reported to be associated with gingival barrier dysfunction, but the effect and underlying mechanism are inconclusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) of gingiva from leptin receptor-deficient mice (db/db) to examine the gingival heterogeneity in the context of T2D. Periodontal health of control mice is characterized by populations of Krt14+-expressing epithelial cells and Col1a1+-fibroblasts mediating immune homeostasis primarily through the enrichment of innate lymphoid cells. The db/db gingiva exhibited decreased epithelial/stromal ratio and dysfunctional barrier. We further observed stromal, particularly fibroblast immune hyperresponsiveness, linked to the recruitment of myeloid-derived cells at the db/db gingiva. Both scRNA-seq and histological analysis suggested the inflammatory signaling between fibroblasts and neutrophils as a potential driver of diabetes-induced periodontal damage. Notably, the "immune-like" stromal cells were wired toward the induction of gingival IL-17A hyperresponsiveness in db/db mice. Our work reveals that the "immune-like" fibroblasts with transcriptional diversity are involved in the innate immune homeostasis at the diabetic gingiva. It highlights a potentially significant role of these cell types in its pathogenesis.

Impact of maternal age on perinatal outcomes in twin pregnancies: a systematic review and meta-analysis.

OBJECTIVE: Current evidence of the maternal, perinatal and neonatal outcomes in twin pregnancies among mothers with advanced age is unclear, especially for mothers with age above 40 years. MATERIALS AND METHODS: A systematic search was conducted using the PubMed, Scopus, and Google Scholar databases. Studies that were observational in design or analysed retrospective data were considered for inclusion. The included studies had to be conducted in twin pregnancies and should have documented the effect of maternal age on obstetric and/or neonatal outcomes. Statistical analysis was performed using STATA software. RESULTS: A total of 20 studies were considered for inclusion. All the studies were based on retrospective data. Compared to mothers aged under 40 years, those with advanced age (≥40 years) had increased risk of caesarean delivery [RR 1.20, 95% CI: 1.05, 1.37], gestational hypertension [RR 2.71, 95% CI: 1.72, 4.27], gestational diabetes mellitus [RR 2.03, 95% CI: 1.28, 3.21], preterm birth [RR 2.47, 95% CI: 1.09, 5.80], neonatal admission to intensive care unit [RR 1.78, 95% CI: 1.21, 2.64] and perinatal and/or neonatal mortality [RR 5.76, 95% CI: 1.11, 29.7]. The risk of gestational diabetes mellitus [RR 1.52, 95% CI: 1.21, 1.90] and having caesarean delivery [RR 1.19, 95% CI: 1.10, 1.28] was higher in mothers with ≥35 years of age, compared to those <35 years. There were no significant differences in the risk of adverse neonatal outcomes among the mothers with age ≥35 years. However, in these mothers, the risk of perinatal/neonatal mortality [RR 0.82, 95% CI: 0.76, 0.88] was comparatively lower than in mothers under 35 years of age. There appeared no significant risk of advanced maternal age for postpartum haemorrhage, hospitalization during pregnancy and premature rupture of membranes. CONCLUSIONS: The increased risk of maternal, neonatal and perinatal outcomes in mothers with advanced age highlights the need for close follow-up, early detection and management of medical complications in twin pregnancies.

[Analysis of gene variation and clinical characteristics of Wiedemann-Steiner syndrome].

Objective: To summarize and analyze the clinical characteristics and gene mutations of 6 patients with Wiedemann-Steiner syndrome (WDSTS). Methods: To review and analyze the clinical data, including general conditions, clinical manifestations, growth hormone, cranial or pituitary gland magnetic resonance imaging (MRI),gene results and other data, 6 cases with WDSTS admitted to the Department of Endocrinology, Genetics and Metabolism of Jiangxi Provincial Children's Hospital and the Department of Child Care of Pingxiang Maternity and Child Care from April 2017 to February 2021 were recruited. Results: Of the 6 patients, 2 were male and 4 were female. The age of the first visit ranged from 1.0 to 11.2 years. All the 6 children presented with growth retardation and mental retardation and they all had typical facial dysmorphism and hypertrichosis (mainly on the back and limbs). Among them, case 5 had a growth hormone deficiency, and case 2 and 4 had abnormalities revealed by cranial MRI. Variations in KMT2A gene were identified in these 6 patients: c.10900+2T>C,c.10837C>T(p.Gln3613*), c.4332G>A(p.E1444E), c.2508dupC(p.W838Lfs*9), c.11695_11696delinsT(p.T3899Sfs*73), c.9915dupA (p.P3306Tfs*22).Among these variations, c.4332G>A, c.11695_11696delinsT and c.9915dupA were novel mutations. Therefore, the final diagnosis of these patients was WDSTS. Conclusions: Patients presented with short stature and mental retardation, typical facial dysmorphism and hypertrichosis should be considered WDSTS. Whole-exome sequencing plays an important role in disease diagnosis and genetic counseling.

Manganese promoted wheat straw decomposition by regulating microbial communities and enzyme activities.

AIMS: This study investigated the dose-effect of manganese (Mn) addition on wheat straw (WS) decomposition, and explored the potential mechanisms of Mn involved in the acceleration of WS decomposition in regards to the soil microbial communities and enzyme activities. METHODS AND RESULTS: A 180-day incubation experiment was performed to examine the decomposition of WS under four Mn levels, that is, 0, 0.25, 1 and 2 mg g-1 . The effects of microbial communities and enzyme activities were evaluated using control (0 mg g-1 ) and Mn (0.25 mg g-1 ) treatments. Our results revealed that Mn (0.25 mg g-1 ) addition significantly increased WS decomposition, and enhanced the release of carbon and nitrogen. Optimal Mn addition (0.25 mg g-1 ) also caused significant increases in the activity of neutral xylanase (NEX), laccase (Lac), manganese peroxidase (MnP) and lignin peroxidase (LiP) within the incubation period. Mn (0.25 mg g-1 ) addition also enriched some operational taxonomic units (OTUs) that, in turn, had the potential ability to decompose crop straw, such as secreting lignocellulolytic enzymes. CONCLUSIONS: Mn (0.25 mg g-1 ) could promote WS decomposition through enrichment of the microbial species involved in biomass decomposition, which enhanced the lignocellulose-degrading enzyme activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidence for Mn to promote WS biodegradation after Mn application, opening new windows to improve the utilization efficiency of crop residues.

The characteristics and risk factors of the postoperative nausea and vomiting in female patients undergoing laparoscopic sleeve gastrectomy and laparoscopic gynecological surgeries: a propensity score matching analysis.

OBJECTIVE: The aim of this study was to compare the prevalence of postoperative nausea and vomiting (PONV) in matched patients undergoing laparoscopic sleeve gastrectomy (LSG) and laparoscopic gynecological surgeries (LGS) and investigate the main cause of the high occurrence of PONV in bariatric surgeries. PATIENTS AND METHODS: Medical records of female patients with a body mass index (BMI) greater than 30 kg/m2 undergoing LSG or LGS from January 1, 2016 to September 1, 2020 were reviewed for PONV episodes in the first postoperative 48 hours. A 1:1 propensity score matching (PSM) method was performed between cases subject to the two types of surgery, and PONV rates were compared. RESULTS: A total of 278 patients met the inclusion criteria (LSG = 101, LGS = 177), and 74 matched subjects were selected from each group after PSM. An increased occurrence of PONV was noted in female patients with LSG compared with those undergoing LGS (66.2% vs. 23.0%; p<0.001). PONV severity was significantly worse in the LSG (p<0.001), and more frequent use of rescue antiemetics was detected in the LSG group compared with the LGS group (51.4% vs. 17.6%; p<0.001). The time of the first use of rescue drugs was much earlier in the LGS group (p = 0.034). CONCLUSIONS: Female patients undergoing LSG are at increased risk of PONV compared with those with LGS, indicating a critical role of procedure-related alterations of gastric physiology in the high occurrence of PONV after bariatric surgery.

The relationship between endoplasmic reticulum stress and liver function, insulin resistance and vascular endothelial function in patients with non-alcoholic fatty liver disease.

OBJECTIVE: The aim of the study was to investigate the relationship between ER stress and liver function, insulin resistance and vascular endothelial function in patients with non-alcoholic fatty liver disease. PATIENTS AND METHODS: A total of 95 patients with non-alcoholic fatty liver disease were selected. They were admitted to our hospital from November 2016 to January 2019. A total of 90 cases of obese patients without fatty liver were selected as control group during the same period. The levels of ER stress marker protein were compared between the two groups, and the relationship between ER stress and liver function, insulin resistance, and vascular endothelial function was analyzed. RESULTS: The protein level of ER stress markers in the test group was significantly higher than that in the control group (p<0.05). The liver function index and insulin resistance level were significantly higher than those in the control group (p<0.05). The level of vascular endothelial function was significantly lower than that of the control group (p<0.05). Pearson correlation analysis showed that ER stress marker protein was positively correlated with liver function and insulin resistance (p<0.05), while ER marker protein was negatively correlated with vascular endothelial function (p<0.05). CONCLUSIONS: Liver function and insulin resistance are closely related to ER stress in patients with non-alcoholic fatty liver disease. Insulin resistance is one of the factors inducing and aggravating endothelial dysfunction.

[Open hepatectomy versus laparoscopic in the treatment of primary left-sided hepatolithiasis: a propensity, long-term follow-up analysis at a single center].

To compare short-term and long-term efficacy after laparoscopic left hepatectomy(LLR) to open left hepatectomy(OLH) for primary left-sided hepatolithiasis. Methods: Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ(2) test or Fisher test. Results: No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ(2)=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ(2)=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ(2)=4.029, P=0.045). OLH (95% CI: 1.55 to 10.75, P=0.004) and postoperative complications (95% CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95% CI: 1.428 to 44.080, P=0.018) and residual stones (95% CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95% CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion: Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

LepR-Expressing Stem Cells Are Essential for Alveolar Bone Regeneration.

Stem cells play a critical role in bone regeneration. Multiple populations of skeletal stem cells have been identified in long bone, while their identity and functions in alveolar bone remain unclear. Here, we identified a quiescent leptin receptor-expressing (LepR+) cell population that contributed to intramembranous bone formation. Interestingly, these LepR+ cells became activated in response to tooth extraction and generated the majority of the newly formed bone in extraction sockets. In addition, genetic ablation of LepR+ cells attenuated extraction socket healing. The parabiosis experiments revealed that the LepR+ cells in the healing sockets were derived from resident tissue rather than peripheral blood circulation. Further studies on the mechanism suggested that these LepR+ cells were responsive to parathyroid hormone/parathyroid hormone 1 receptor (PTH/PTH1R) signaling. Collectively, we demonstrate that LepR+ cells, a postnatal skeletal stem cell population, are essential for alveolar bone regeneration of extraction sockets.

Risk factors for death from hand-foot-mouth disease: a meta-analysis.

In recent years, outbreaks of hand-foot-mouth disease (HFMD) in China, Singapore and other Western Pacific Region, involving millions of children, have become a big threat to public health. This study aimed to quantitatively assess all qualified studies and identify the risk factors for HFMD death. A systematic search of the databases PubMed, Medline, Embase and the Cochrane Library was performed. Study heterogeneity and publication bias were estimated. Seven case-control studies involving 1641 participants (634 died and 1007 survived) were included in the meta-analysis. Human enterovirus 71 infection, male, age ⩽3 years, vomiting, cyanosis, convulsion, duration of fever ⩾3 days, atypical rashes and abdominal distention were not significantly related to HFMD death (P ⩽ 0.05). Lethargy (odds ratio (OR) = 6.62; 95% CI 3.61-12.14; I2 = 0%; P < 0.0001), pneumonoedema/pneumorrhagia (OR = 4.09; 95% CI 2.44-6.87; I2 = 0%; P < 0.0001), seizures (OR = 6.85; 95% CI 2.37-19.74; I2 = 0%; P = 0.0004), dyspnoea (OR = 8.24; 95% CI 2.05-33.19; I2 = 83%; P = 0.003) and coma (OR = 3.76; 95% CI 1.85-7.67; I2 = 0%; P = 0.0003) were significantly associated with HFMD death, which were risk factors for HFMD death.

Phase-Field Simulation of Grain Boundary Evolution In Microstructures Containing Second-Phase Particles with Heterogeneous Thermal Properties.

Understanding the interaction between complex thermal fields and metallic structures at the meso-scale is crucial for the prediction of microstructural evolution during thermomechanical processing. The competitive growth of crystal grains, driven by thermodynamic forces at the grain boundaries, is one of the most fundamental phenomena in metallurgy and solid state physics. The presence of second phase particles, which act as pinning sites for boundaries, drastically alters the coarsening behaviour of the system; particularly when considering that these particles have different thermal properties to the primary phase. In this work a multi-phase field model, incorporating thermal gradient and curvature driving forces, is used to predict grain growth in a Ti6Al4V alloy system with second phase particle inclusions representative of oxide and carbide precipitates. The multi-phase field framework is fully coupled to the heat equation. The incorporation of the thermal gradient driving force enables the detailed behaviour of the grain boundaries around the particles to be predicted. It is shown that the inclusion of particles with a lower thermal conductivity has a significant influence on the coarsening behaviour of various systems of grains, due to the combined effects of thermal shielding and the generation of thermal gradient driving forces between the boundaries and pinning particles.

2Hz-electroacupuncture attenuates heroin-seeking behaviors via adjusts CB1-Rs and CB2-Rs expression in relapse-relevant brain regions of heroin self-administration rats.

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

[Etiological analysis of hepatopathy of unknown etiology in 470 cases undergoing routine liver biopsy examination].

Objective: To understand the etiology of hepatopathy of unknown etiology in patients undergoing liver biopsy. Methods: Demographic data and pathological examination reports of patients with hepatopathy of unknown etiology who underwent liver biopsy examination at outpatient and inpatient of the Second Hospital of Nanjing between January 2017 and June 2018 were retrospectively collected. All liver histopathological sections combined with clinical and pathological features based on liver biopsy examinations were diagnosed by a reputed clinician and a pathologist. Results: A total of 470 cases with hepatopathy of unknown etiology who underwent liver biopsy were enrolled. Of these, 425 cases (90.4%) had a definite diagnosed disease after comprehensive analysis of pathological and clinical data. The diagnosis of hepatopathy of unknown etiology included 11 diseases: 90 cases with autoimmune hepatitis had autoimmune liver disease (19.1%), 38 cases had primary biliary cholangitis (8.1%), 43 cases with overlap syndrome of autoimmune hepatitis had primary biliary cholangitis (9.1%), 118 cases had drug-induced liver injury (25.1%), 75 cases had nonalcoholic fatty liver disease (NAFLD) (16.0%), 12 cases had alcoholic liver disease (2.6 cases) %), 15 cases (3.2%) had vascular liver disease, 7 cases (1.5%) had hereditary metabolic liver disease, 5 cases (1.1%) had other systemic diseases, 16 cases (3.4%) had more than two kinds of liver diseases, and 6 cases (1.3%) had others rare liver diseases. Conclusion: Over 90% cause of the hepatopathy of unknown etiology in the long run can be determined, and the main causes are autoimmune liver disease, drug-induced liver injury, and nonalcoholic fatty liver disease, which needs multidisciplinary cooperation to diagnose, and clinicians need to master the basic and clinical knowledge of liver diseases as well as liver pathology, hepatobiliary imaging, and genetics.

[Two cases report of laryngeal malignant melanoma and a review of literatures].

Summary Two patients both complained of one year history of hoarseness and the clinical manifestations and imageology among 2 patients were lack of specificity. The pathological tissue was successfully eradicated by surgical removal. Histopathology established laryngeal malignant melanoma as the diagnosis. The clinical manifestations and imageology were lack specificity between laryngeal malignant melanoma, laryngeal cancer and other malignant tumor, the diagnosis is difficult, often confirmed by postoperative pathology, the treatment is often by surgery and have a poor prognosis.

[Rapeutic effect analysis of the auricle appliance on 2-6 months old infants with congenital auricle deformity].

Objective: To study the effect of amazing ear correction system on 2-6 months old infants with congenital ear deformity. Method: Thirty infants (37 ears) with congenital auricular deformities were enrolled in the study. Deformities included constriction, cryptopia, helicalrim, prominent, conchal strut, and Stahl deformities and microtia. The patients were divided into 2 groups. Infants elder than 2 months were 20 cases(26 auricular malformed ears). And infants under 2 months old were 10 cases(11 auricular malformed ears). All the patients underwent ear molding using the amazing ears correction system. The patients of each group were followed-up for at least 3 months. Result: The results were divided into three levels(excellent, good, and poor) according to the correction of auricular shape. In Group elder than 2 months, 13 ears were excellent and the average treatment time was 46.85 days，5 ears were good, the average treatment time was 43.40 days and 8 ears were poor, the average treatment time was 13.13 days. In Group under 2 months old, 5 ears were excellent and the average treatment time was 28.80 days，6 ears were good and the average treatment time was 18.66 days. The patients of each group were followed-up for at least 3 months and no rebound occurred. Conclusion:Ear correction system has a significant effect on those more than 2 months and less than 6 months with congenital auricular deformity. The children who were more than 2 months old need to wear the auricle appliance over 6 weeks to achieve a satisfactory effect.