Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia.

Chronic hypoxia, common in neonates, disrupts gut microbiota balance, which is crucial for brain development. This study utilized cyanotic congenital heart disease (CCHD) patients and a neonatal hypoxic rat model to explore the association. Both hypoxic rats and CCHD infants exhibited brain immaturity, white matter injury (WMI), brain inflammation, and motor/learning deficits. Through 16s rRNA sequencing and metabolomic analysis, a reduction in B. thetaiotaomicron and P. distasonis was identified, leading to cholic acid accumulation. This accumulation triggered M1 microglial activation and inflammation-induced WMI. Administration of these bacteria rescued cholic acid-induced WMI in hypoxic rats. These findings suggest that gut microbiota-derived cholic acid mediates neonatal WMI and brain inflammation, contributing to brain immaturity under chronic hypoxia. Therapeutic targeting of these bacteria provides a non-invasive intervention for chronic hypoxia patients.

Fluoride Doping Na3 Al2/3 V4/3 (PO4 )3 Microspheres As Cathode Materials for Sodium-Ion Batteries with Multielectron Redox.

Sodium-ion batteries (SIBs) are potential candidates for large energy storage usage because of the natural abundance and cheap sodium. Nevertheless, improving the energy density and cycling steadiness of SIB cathodes remains a challenge. In this work, F-doping Na3 Al2/3 V4/3 (PO4 )3 (NAVP) microspheres (Na3 Al2/3 V4/3 (PO4 )2.9 F0.3 (NAVPF)) are synthesized via spray drying and investigated as SIB cathodes. XRD and Rietveld refinement reveal expanded lattice parameters for NAVPF compared to the undoped sample, and the successful cation doping into the Na superionic conductor (NASICON) framework improves Na+ diffusion channels. The NAVPF delivers an ultrahigh capacity of 148 mAh g-1 at 100 mA g-1 with 90.8% retention after 200 cycles, enabled by the activation of V2+ /V5+ multielectron reaction. Notably, NAVPF delivers an ultrahigh rate performance, with a discharge capacity of 83.6 mAh g-1 at 5000 mA g-1 . In situ XRD demonstrates solid-solution reactions occurred during charge-discharge of NAVPF without two-phase reactions, indicating enhanced structural stability after F-doped. The full cell with NAVPF cathode and Na+ preintercalated hard carbon anode shows a large discharge capacity of 100 mAh g-1 at 100 mA g-1 with 80.2% retention after 100 cycles. This anion doping strategy creates a promising SIB cathode candidate for future high-energy-density energy storage applications.

Intracellular presence of Helicobacter pylori antigen and genes within gastric and vaginal Candida.

BACKGROUND: Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida. METHODS: Candida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity. RESULTS: A total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive. CONCLUSION: In the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity.

[Clinical features and genetic analysis of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome due to variants of FOXP3 gene].

OBJECTIVE: To analyze the clinical characteristics of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. METHODS: Three patients with IPEX syndrome diagnosed at the Children's Hospital of Fudan University from January 24, 2013 to July 29, 2019 were selected as the study subjects. Their clinical features, laboratory investigations and results of genetic testing were summarized. Treatment and prognosis were also explored. RESULTS: All of the three children had developed the disorder during infancy. One child had initial features including diabetes and diabetic ketoacidosis, whilst the other two had initiated by diarrhea. All patients had gastrointestinal involvement, and one was diagnosed as very early onset inflammatory bowel disease by colonoscopy and biopsy. Two children also had endocrine glands involvement. One child had manifested type 1 diabetes and positivity for thyroglobulin and thyroid peroxidase antibodies, though his thyroid function had remained normal. Another one had hypothyroidism and was treated by levothyroxine. Genetic testing revealed that all children had harbored missense variants of the FOXP3 gene, including c.1222G>A (p.V408M), c.767T>C (p.M256T) and c.1021A>G (p.T341A). The clinical symptoms of one patient were alleviated following allogeneic hematopoietic stem cell transplantation. One patient was stable after treatment with infliximab plus insulin, and one child had died of refractory septic shock and multiple organ dysfunction syndrome at 3 months old. CONCLUSION: FOXP3 gene variant-associated IPEX syndrome may have very early onset and diverse clinical manifestations. For male patients with infantile onset chronic diarrhea, multiple endocrine or multiple system involvement, genetic testing is recommended, which may facilitate early diagnosis, treatment and genetic counseling.

HDAC9 inhibition reduces skeletal muscle atrophy and enhances regeneration in mice with cigarette smoke-induced COPD.

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD), and sarcopenia is one of the significant comorbidities of COPD. However, the pathogenesis of CS-related deficient skeletal muscle regeneration has yet to be clarified. The impact of CS on myoblast differentiation was examined, and then we determined which HDAC influenced the myogenic process and muscle atrophy in vitro and in vivo. Finally, we further investigated the potential mechanisms via RNA sequencing. Long-term CS exposure activated skeletal muscle primary satellite cells (SCs) while inhibiting differentiation, and defective myogenesis was also observed in C2C12 cells treated with CS extract (CSE). The level of HDAC9 changed in vitro and in vivo in CS exposure models as well as COPD patients, as detected by bioinformatics analysis. Our data showed that CSE impaired myogenic capacity and myotube formation in C2C12 cells via HDAC9. Moreover, inhibition of HDAC9 in mice exposed to CS prevented skeletal muscle dysfunction and promoted SC differentiation. The results of RNA-Seq analysis and verification indicated that HDAC9 knockout improved muscle differentiation in CS-exposed mice, probably by acting on the AKT/mTOR pathway and inhibiting the P53/P21 pathway. More importantly, the serum of HDAC9 KO mice exposed to CS alleviated the differentiation impairment of C2C12 cells caused by serum intervention in CS-exposed mice, and this effect was inhibited by LY294002 (an AKT/mTOR pathway inhibitor). These results suggest that HDAC9 plays an essential role in the defective regeneration induced by chronic exposure to CS.

Screening and validation of differentially expressed genes in adipose tissue of patients with obesity and type 2 diabetes mellitus.

White adipose tissue (WAT) plays a pivotal role in the onset of type 2 diabetes mellitus (T2DM) and obesity. Despite its significance the underlying pathogenesis and key genes associated with it remain elusive. In our study, we screened the differentially expressed genes (DEGs) in intra-abdominal WAT of T2DM patients with obesity, as well as those with simple obesity, aiming to lay a foundational theory for an in-depth investigation of T2DM pathogenesis and the identification of novel therapeutic targets. Gene expression datasets (GSE16415 and GSE71416) were retrieved from the Gene Expression Omnibus (GEO) database. We employed R for screening DEGs and conducted a functional enrichment analysis using the Metascape database. Combined Lasso regression and Boruta feature selection algorithms were used to identify key DEGs. Subsequently, these were cross-verified using the GSE29231 dataset. Samples and medical records were collected from clinical study participants. The mRNA and protein expressions of the key DEGs were verified using qRT-PCR and western blotting, respectively. We discerned a total of 130 DEGs, with 40 being upregulated and 90 downregulated. Functional and pathway enrichment analyses illuminated that these genes are instrumental in mediating metabolite and energy production, neutrophil-mediated immunity, and other associated biological processes. This includes their involvement in the tricarboxylic acid cycle, glycolysis/gluconeogenesis, peroxisome proliferator-activated receptors, and other signalling pathways. Two genes, CIDEA and FSCN1 emerged as key DEGs. The low expression of CIDEA and high expression of FSCN1 in the T2DM and obesity group were verified in clinical samples (P < 0.05). We established that CIDEA and FSCN1 manifest significant differential expression in T2DM patients who are obese. This suggests their potential as risk assessment markers and therapeutic targets for T2DM.

Efficacy and safety of endoscopic retrograde cholangiopancreatography in recurrent pancreatitis of pediatric asparaginase-associated pancreatitis.

BACKGROUND: Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective. AIM: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP. METHODS: From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared. RESULTS: The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication. CONCLUSION: ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

Co-Solvent Electrolyte Design to Inhibit Phase Transition toward High Performance K+ /Zn2+ Hybrid Battery.

Manganese hexacyanoferrate (MnHCF) is one of the most promising cathode materials for aqueous battery because of its non-toxicity, high energy density, and low cost. But the phase transition from MnHCF to Zinc hexacyanoferrate (ZnHCF) and the larger Stokes radius of Zn2+ cause rapid capacity decay and poor rate performance in aqueous Zn battery. Hence, to overcome this challenge, a solvation structure of propylene carbonate (PC)-trifluoromethanesulfonate (Otf)-H2 O is designed and constructed. A K+ /Zn2+ hybrid battery is prepared using MnHCF as cathode, zinc metal as anode, KOTf/Zn(OTf)2 as the electrolyte, and PC as the co-solvent. It is revealed that the addition of PC inhabits the phase transition from MnHCF to ZnHCF, broaden the electrochemical stability window, and inhibits the dendrite growth of zinc metal. Hence, the MnHCF/Zn hybrid co-solvent battery exhibits a reversible capacity of 118 mAh g-1 and high cycling performance, with a capacity retention of 65.6% after 1000 cycles with condition of 1 A g-1 . This work highlights the significance of rationally designing the solvation structure of the electrolyte and promotes the development of high-energy-density of aqueous hybrid ion batteries.

External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children: A multicenter randomized controlled trial.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children. AIM: To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children. METHODS: This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated. RESULTS: A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed. CONCLUSION: External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.

Ethnicity and sex-specific 99th percentile upper reference limits of high-sensitivity cardiac troponin I among adults in Xinjiang, China.

OBJECTIVES: To determine the 99th percentile upper reference limit (URL) of high-sensitivity cardiac troponin I (hs-cTnI) in a healthy population in Xinjiang, China, and investigate the impact of ethnicity, sex, and age on this limit. DESIGN AND METHODS: From September 2018 to March 2022, 5,090 Han and Uyghur adults aged 20-79 years were recruited. After questionnaire screening, 2,970 participants with physical and/or laboratory normality were enrolled. Participants recruited between September 2018 and October 2021 (2,109/2,970) were evaluated by ARCHITECTi2000 to determine the 99th percentile URL of hs-cTnI. The results were then validated in 861/2,970 participants recruited from November 2021 to March 2022. A criterion of ≤ 10% of test results falling outside the original determined value was used to determine whether the newly established reference intervals were valid. RESULTS: The hs-cTnI concentration was higher among Uyghurs than among Han participants (p < 0.001). The 99th percentile URLs were 17.52 ng/L for all participants, 18.96 ng/L for Uyghur, and 16.93 ng/L for Han. Hs-cTnI concentration was also correlated with sex and age. In the Han and Uyghur groups, male participants had a higher hs-cTnI concentration than female participants (p < 0.001); the 99th percentile URLs of hs-cTnI among male and female participants were 17.80 vs. 13.67 ng/L and 19.47 vs. 16.52 ng/L, respectively. Stratified by age, hs-cTnI concentrations were higher in participants aged > 60 years than in those of other age categories (p < 0.001), in both the Han and Uyghur groups. Finally, <2% of these test results exceeded the newly established reference, validating the results. CONCLUSIONS: This study established the 99th percentile URLs of hs-cTnI in the Xinjiang. Ethnicity and sex influence the value and should be considered.

Resveratrol Prevents Skeletal Muscle Atrophy and Senescence via Regulation of Histone Deacetylase 2 in Cigarette Smoke-Induced Mice with Emphysema.

Objective: The aim of this study was to investigate the effects of resveratrol (RSV) on cigarette smoke (CS)-induced skeletal muscle atrophy and senescence in mice with emphysema and to explore the underlying mechanisms. Methods: Gastrocnemius muscle weight and lung and muscular morphology were observed in CS-exposed mice with or without RSV treatment. The expression of atrophy-related markers (MURF1 and MAFbx), senescence-related markers (P53, P21 and SMP30) and NF-κB inflammatory pathways was detected by Western blotting and real-time PCR. The levels of IL-1ß and TNF-α were also determined by ELISA, and the number of senescent cells was determined by SA-ß gal staining. In addition, the expression of HDAC2 and the effect of HDAC2 on CSE-induced skeletal muscle atrophy and senescence by RSV treatment were investigated. Results: RSV prevented emphysema and skeletal muscle atrophy in long-term CS-exposed mice. RSV decreased the expression of MURF1, MAFbx, P53, and P21 and inhibited the NF-κB pathway both in vivo and in vitro. Moreover, RSV reversed CS-induced downregulation of HDAC2 expression both in gastrocnemius and in C2C12 cells. Moreover, knockdown of HDAC2 significantly abolished the inhibitory effect of RSV on the expression of MURF1, MAFbx, P53, P21 and inflammatory factors (IL-1ß and TNF-α) in C2C12 cells. Conclusion: RSV prevents CS-induced skeletal muscle atrophy and senescence, and upregulation of HDAC2 expression and suppression of inflammation are involved.

Risk factors for the progression from acute recurrent to chronic pancreatitis among children in China.

Background: Risk factors for progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children are poorly understood. Aim: To summarize the clinical characteristics of children with ARP and CP, identify the risk factors of CP, and investigate the factors associated with rapid progression from initial onset of ARP to CP. Methods: The following variables were included in the risk factor analysis: sex, age at onset, family history, pancreas or biliary tract structural abnormalities, and genetic variations. Univariate and multivariate logistic regression analyses were used to assess the risk factors of CP. The Kaplan-Meier curves of the ARP progression to CP for various risk factor groupings were constructed and compared using the log-rank test. The Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR) of progression to CP for each risk variable. Results: In total, 276 children were studied, of whom 136 progressed to CP. Among them, 41 had pancreatic duct obstructive disease; 105 underwent genetic testing, of whom 68 were found to have genetic variations. Among the remaining 140 patients who did not progress to CP, 61 had biliary obstructions. Forty-three of these children underwent genetic testing, and 15 were found to have genetic variations. Risk factor analysis showed that children with gene mutations were at a higher risk of progressing to CP [odds ratio (OR) = 3.482; 95% confidence interval (CI): 1.444-8.398; P = 0.005]; children with pancreas divisum (PD) had a higher risk of CP than those without (OR = 8.665; 95% CI: 1.884, 9.851; P = 0.006). Further, children whose first ARP occurred at an older age might develop CP faster (HR = 1.070; 95% CI: 1.003, 1.141; P = 0.039). Children with gene mutations had a faster rate of progression to CP after onset than children without gene mutations (HR = 1.607; 95% CI: 1.024, 2.522; P = 0.039), PRSS1 gene mutations were more associated (P = 0.025). There was no difference in the rate of progression from ARP to CP in children with PD (P = 0.887); however, endoscopic retrograde cholangiopancreatography (ERCP) intervention delayed the progression to CP in ARP patients with PD (P = 0.033). Conclusion: PRSS1 gene mutations and PD are key risk factors for ARP progression to CP in children. PD itself does not affect the disease progression rate, but therapeutic ERCP can be beneficial to patients with ARP with symptomatic PD and delay the progression to CP.

Correlation analysis of gastric mucosal lesions with Helicobacter pylori infection and its virulence genotype in Guiyang, Guizhou province, China.

Background: Helicobacter Pylori (H. pylori) infection is the most important factor affecting clinical outcome in patients with gastric mucosal lesions. This study aimed to investigate H. pylori infection in patients with gastric mucosal lesions and their virulence genotype in Guiyang, China. Methods: Pathological examinations of 1,364 biopsies from patients with upper gastrointestinal symptoms and H. pylori infection were analyzed according to different pathological types. The bacterial genome DNA was extracted from H. pylori strains isolated from gastric biopsies, and the cagA, vacA, and iceA virulence genes were detected and typed to analyze the correlation of their genotypes between different pathological lesions. Results: The positive rate of H. pylori infection was approximately 19.9% (272/1,364), as determined by histopathological examination (HPE). It was more frequently detected in men than in women. A total of 85 H. pylori isolates were obtained from 280 clinical samples (positive rate 30.4%, 85/280). Of these 85 strains, cagA, vacA, and iceA genes were identified in 85.9%, 100%, and 83.5% of samples, respectively. Approximately 74.1% of strains were cagA East Asian type (cagA-ABD), and 11.8% of were cagA Western strains (cagA-AB, cagA-ABC), only present in patients with chronic non-atrophic gastritis. Gastric intraepithelial neoplasia and gastric cancer harbored both Asian strains. A total of 7 combinations of vacA genotypes were noted, among which s1c/m1b (30.6%) and s1c/m2 (41.2%) were the dominant genotypes. The predominant iceA genotype was iceA1 (64.7%). Conclusions: We observed that the positive rate of H. pylori infection was related to the pathological type of patients' gastric mucosal lesions. Isolated H. pylori strains showed a unique genotype, mainly East Asian type cagA (ABD), vacA s1c/m2 genotype, and iceA1. These results provide an important reference for further studies of H. pylori in Guizhou province, China.

Analysis of the Efficacy and Safety of Endoscopic Retrograde Cholangiopancreatography in Children With Symptomatic Pancreas Divisum.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly performed in children with symptomatic pancreas divisum (PD). Aim: To investigate the safety and efficacy of ERCP in the treatment of children with symptomatic PD. Methods: We performed a retrospective analysis on children with PD who were treated with ERCP at Shanghai Children's Medical Center between June 2015 and May 2020. Pertinent patient, clinical and procedural data were collected to assess the therapeutic effects and identify the risk factors for post-ERCP pancreatitis (PEP). Results: Overall, 114 ERCPs were performed in 46 children with PD. With a median follow-up of 28.5 months (12-71 months), 40 (87.0%) children achieved clinical remission, the median number of acute pancreatitis episodes decreased from four times per year pre-operatively to once per year post-operatively (P < 0.001), and the nutritional score improved post-operatively (P = 0.004). The incidence of PEP was 7.9%, and female sex, stone extraction, and gene mutations were identified as possible risk factors for PEP on univariate analysis. However, there was no statistical significance on multivariate analysis (P > 0.05). Conclusion: Therapeutic ERCP is an effective and safe intervention for children with symptomatic PD.

Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes.

Type 2 diabetes (T2D) is thought to be a complication of metabolic syndrome caused by disorders of energy utilization and storage and characterized by insulin resistance or deficiency of insulin secretion. Though the mechanism linking obesity to the development of T2D is complex and unintelligible, it is known that abnormal lipid metabolism and adipose tissue accumulation possibly play important roles in this process. Recently, nicotinamide N-methyltransferase (NNMT) has been emerging as a new mechanism-of-action target in treating obesity and associated T2D. Evidence has shown that NNMT is associated with obesity and T2D. NNMT inhibition or NNMT knockdown significantly increases energy expenditure, reduces body weight and white adipose mass, improves insulin sensitivity, and normalizes glucose tolerance and fasting blood glucose levels. Additionally, trials of oligonucleotide therapeutics and experiments with some small-molecule NNMT inhibitors in vitro and in preclinical animal models have validated NNMT as a promising therapeutic target to prevent or treat obesity and associated T2D. However, the exact mechanisms underlying these phenomena are not yet fully understood and clinical trials targeting NNMT have not been reported until now. Therefore, more researches are necessary to reveal the acting mechanism of NNMT in obesity and T2D and to develop therapeutics targeting NNMT.

Histone Deacetylase 2 Suppresses Skeletal Muscle Atrophy and Senescence via NF-κB Signaling Pathway in Cigarette Smoke-Induced Mice with Emphysema.

Background: Exposure to cigarette smoke (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD). CS not only causes chronic airway inflammation and lung damage but also is involved in skeletal muscle dysfunction (SMD). Previous studies have shown that histone deacetylase 2 (HDAC2) plays an important role in the progression of COPD. The aim of this study was to determine the role of HDAC2 in CS-induced skeletal muscle atrophy and senescence. Methods: Gastrocnemius muscle weight and cross-sectional area (CSA) were measured in mice with CS-induced emphysema, and changes in the expression of atrophy-related markers and senescence-related markers were detected. In addition, the relationship between HDAC2 expression and skeletal muscle atrophy and senescence was also investigated. Results: Mice exposed to CS for 24 weeks developed emphysema and gastrocnemius atrophy and exhibited a decrease in gastrocnemius weight and skeletal muscle cross-sectional area. In addition, the HDAC2 protein levels were significantly decreased while the levels of atrophy-associated markers, including MURF1 and MAFbx, and senescence-associated markers, including P53 and P21, were significantly increased in the gastrocnemius muscle. In vitro, the exposure of C2C12 cells to cigarette smoke extract (CSE) significantly increased the MAFbx and MURF1 protein levels and decreased the HDAC2 protein levels. Moreover, overexpression of HDAC2 significantly ameliorated CSE-induced atrophy and senescence and reversed the increased MURF1, MAFbx, P53, and P21 expression in C2C12 cells. In addition, CSE treatment significantly increased the IKK and NF-κB p65 protein levels, and PTDC (an NF-kB inhibitor) ameliorated atrophy and senescence. Conclusion: Our findings suggest that HDAC2 plays an important role in CS-induced skeletal muscle atrophy and senescence, possibly through the NF-κB pathway.

Web-based calculator for biliary atresia screening in neonates and infants with cholestasis.

BACKGROUND: Distinguishing biliary atresia from non-biliary atresia in patients with cholestasis is challenging, as these conditions have a similar clinical presentation. We developed and externally validated a screening model for biliary atresia and devised a web-based calculator for use in clinical settings. METHODS: A screening model was developed based on data from 227 cholestatic infants (82 and 145 with and without biliary atresia, respectively) and validated in 234 infants (90 and 144 with and without biliary atresia, respectively) admitted to three hospitals. Variables were selected from routine examination results using the least absolute shrinkage and selection operator method and entered into a logistic regression model to construct a biliary-atresia-risk-predicting equation. Cutoff values for risk stratification were estimated using model sensitivity, derived from the receiver-operating characteristic curves. RESULTS: The final screening model included seven variables (i.e., weight at admission, clay-colored stools, γ-glutamyl transpeptidase and albumin levels at admission, abnormal gallbladder, triangular cord sign, and change in total bilirubin levels). The model generated an area under the curve of 0.94 with a sensitivity of 91.46 and specificity of 86.62 in the derivation cohort. This was confirmed in the validation cohort, as we found an area under the curve of 0.93 with a sensitivity of 93.1 and specificity of 80.15. Patients were stratified into three risk groups (low-, moderate-, and high-risk groups). Biliary atresia was excluded in the low-risk group. The high-risk group showed a higher detection rate of biliary atresia compared to the stool color screening method alone. This model was integrated into a user-friendly web-based system. CONCLUSIONS: The screening tool had a high predictive value and may help in decision-making by physicians at tertiary and community hospitals.

Heterogeneity of Helicobacter pylori Strains Isolated from Patients with Gastric Disorders in Guiyang, China.

PURPOSE: Chronic Helicobacter pylori infection causes peptic ulcers in a subpopulation of individuals and is a risk factor for the development of gastric cancer. Multiple infections and heteroresistant H. pylori contribute to poor treatment efficacy. Here, we investigated the extent of genetic diversity among H. pylori strains within a given host and its influence on the results of antibiotic (metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline) susceptibility testing. MATERIALS AND METHODS: Gastric mucosa biopsy samples were obtained from patients with gastric disorders, including 48 H. pylori positive patients, who were never previously treated for H. pylori infection. Five potential H. pylori colonies isolated from each sample were subcultured for enrichment. Enriched H. pylori colonies were identified through Gram staining and assays for urease, oxidase, and catalase. For each H. pylori monoclonal colony, the antibiotic susceptibility was assessed, genomic DNA was sequenced, and the cytotoxin-associated gene A (cagA) genotype was verified. Co-infection with multiple H. pylori strains was determined using random amplified polymorphic DNA (RAPD)-polymerase chain reaction (PCR). RESULTS: Thirteen gastric mucosa biopsy samples were positive for H. pylori. Five monoclonal strains isolated from each of these 13 patients were identified as H. pylori. RAPD-PCR indicated that intra-patient monoclonal strains of H. pylori in 10 of the 13 samples exhibited heterogeneity. Among the 13 patients, intra-patient monoclonal strains isolated from 4 patients had identical cagA genotype, whereas intra-patient monoclonal strains isolated from the other 9 patients harbored more than one cagA genotype. The antibiotic susceptibility of five intra-patient monoclonal strains from seven patients was inconsistent. CONCLUSION: The existence of heterogeneous H. pylori strains with resistance to different drugs and virulence were common within the gastric mucosa of an individual patient.