Acetylation of xenogeneic silencer H-NS regulates biofilm development through the nitrogen homeostasis regulator in Shewanella.

Adjusting intracellular metabolic pathways and adopting suitable live state such as biofilms, are crucial for bacteria to survive environmental changes. Although substantial progress has been made in understanding how the histone-like nucleoid-structuring (H-NS) protein modulates the expression of the genes involved in biofilm formation, the precise modification that the H-NS protein undergoes to alter its DNA binding activity is still largely uncharacterized. This study revealed that acetylation of H-NS at Lys19 inhibits biofilm development in Shewanella oneidensis MR-1 by downregulating the expression of glutamine synthetase, a critical enzyme in glutamine synthesis. We further found that nitrogen starvation, a likely condition in biofilm development, induces deacetylation of H-NS and the trimerization of nitrogen assimilation regulator GlnB. The acetylated H-NS strain exhibits significantly lower cellular glutamine concentration, emphasizing the requirement of H-NS deacetylation in Shewanella biofilm development. Moreover, we discovered in vivo that the activation of glutamine biosynthesis pathway and the concurrent suppression of the arginine synthesis pathway during both pellicle and attached biofilms development, further suggesting the importance of fine tune nitrogen assimilation by H-NS acetylation in Shewanella. In summary, posttranslational modification of H-NS endows Shewanella with the ability to respond to environmental needs by adjusting the intracellular metabolism pathways.

Elongation factor P modulates Acinetobacter baumannii physiology and virulence as a cyclic dimeric guanosine monophosphate effector.

Cyclic diguanosine monophosphate (c-di-GMP) is widely used by bacteria to control biological functions in response to diverse signals or cues. A previous study showed that potential c-di-GMP metabolic enzymes play a role in the regulation of biofilm formation and motility in Acinetobacter baumannii. However, it was unclear whether and how A. baumannii cells use c-di-GMP signaling to modulate biological functions. Here, we report that c-di-GMP is an important intracellular signal in the modulation of biofilm formation, motility, and virulence in A. baumannii. The intracellular level of c-di-GMP is principally controlled by the diguanylate cyclases (DGCs) A1S_1695, A1S_2506, and A1S_3296 and the phosphodiesterase (PDE) A1S_1254. Intriguingly, we revealed that A1S_2419 (an elongation factor P [EF-P]), is a novel c-di-GMP effector in A. baumannii. Response to a c-di-GMP signal boosted A1S_2419 activity to rescue ribosomes from stalling during synthesis of proteins containing consecutive prolines and thus regulate A. baumannii physiology and pathogenesis. Our study presents a unique and widely conserved effector that controls bacterial physiology and virulence by sensing the second messenger c-di-GMP.

Membrane-enclosed Pseudomonas quinolone signal attenuates bacterial virulence by interfering with quorum sensing.

Outer membrane vesicle (OMV)-delivered Pseudomonas quinolone signal (PQS) plays a critical role in cell-cell communication in Pseudomonas aeruginosa. However, the functions and mechanisms of membrane-enclosed PQS in interspecies communication in microbial communities are not clear. Here, we demonstrate that PQS delivered by both OMVs from P. aeruginosa and liposome reduces the competitiveness of Burkholderia cenocepacia, which usually shares the same niche in the lungs of cystic fibrosis patients, by interfering with quorum sensing (QS) in B. cenocepacia through the LysR-type regulator ShvR. Intriguingly, we found that ShvR regulates the production of the QS signals cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) by directly binding to the promoters of signal synthase-encoding genes. Perception of PQS influences the regulatory activity of ShvR and thus ultimately reduces QS signal production and virulence in B. cenocepacia. Our findings provide insights into the interspecies communication mediated by the membrane-enclosed QS signal among bacterial species residing in the same microbial community.IMPORTANCEQuorum sensing (QS) is a ubiquitous cell-to-cell communication mechanism. Previous studies showed that Burkholderia cenocepacia mainly employs cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) QS systems to regulate biological functions and virulence. Here, we demonstrate that Pseudomonas quinolone signal (PQS) delivered by outer membrane vesicles from Pseudomonas aeruginosa or liposome attenuates B. cenocepacia virulence by targeting the LysR-type regulator ShvR, which regulates the production of the QS signals BDSF and AHL in B. cenocepacia. Our results not only suggest the important roles of membrane-enclosed PQS in interspecies and interkingdom communications but also provide a new perspective on the use of functional nanocarriers loaded with QS inhibitors for treating pathogen infections.

Anti-virulence and bactericidal activities of Stattic against Shigella sonnei.

IMPORTANCE: Shigella sonnei is a major human enteric pathogen that causes bacillary dysentery. The increasing spread of drug-resistant S. sonnei strains has caused an emergent need for the development of new antimicrobial agents against this pathogenic bacterium. In this study, we demonstrate that Stattic employs two antibacterial mechanisms against S. sonnei. It exerted both anti-virulence activity and bactericidal activity against S. sonnei, suggesting that it shows advantages over traditional antibiotics. Moreover, Stattic showed excellent synergistic effects with kanamycin, ampicillin, chloramphenicol, and gentamicin against S. sonnei. Our findings suggest that Stattic has promising potential for development as a new antibiotic or as an adjuvant to antibiotics for infections caused by S. sonnei.

The association between serum 25-hydroxyvitamin D and the prevalence of herpes simplex virus.

Previous studies have reported a potential anti-infection effect for vitamin D. However, the relationship between vitamin D status and herpes simplex virus (HSV) infection has not yet been evaluated. Therefore, this study aimed to determine the association between serum 25-hydroxyvitamin D [25(OH)D] and infection with HSV types 1 and 2 (HSV-1 and HSV-2). Data were collected from the National Health and Nutrition Examination Survey from 2007 to 2016. The association between 25(OH)D and HSV prevalence was evaluated using propensity score matching (PSM) and univariate and multivariate logistic regression analyses. Overall, 14 174 participants were included in the final analysis. Before PSM, 8639 (60.9%) had positive HSV-1 and 2636 (18.6%) had HSV-2. The HSV-1 and HSV-2 positive groups had more females and older individuals (p < 0.05). The HSV-2 patients had lower 25(OH)D levels than those with HSV-1. Age and gender did not differ in the groups after PSM (p > 0.05). The 25(OH)D level was significantly lower in the HSV-1 and HSV-2 groups than in the non-HSV infection groups. Multivariate logistic regression showed that serum 25(OH)D level was negatively associated with HSV-1 and HSV-2 infection (odds ratio [OR] = 0.730 and 0.691, p < 0.001, respectively). Vitamin D deficiency was an independent risk factor for both HSV-1 and HSV-2 (adjusted OR = 2.205 and 2.704, p < 0.001, respectively). Lower serum 25(OH)D levels correlated significantly with increased HSV-1 and HSV-2 infection risk.

Development and validation of a screening method for difficult tracheal intubation based on geometric simulation and computer technology.

BACKGROUND: The anatomical characteristics of difficult airways can be analysed geometrically. This study aims to develop and validate a geometry-assisted difficult airway screening method (GADAS method) for difficult tracheal intubation. METHODS: In the GADAS method, a geometric simulated model was established based on computer graphics. According to the law of deformation of the upper airway on laryngoscopy, the expected visibility of the glottis was calculated to simulate the real visibility on laryngoscopy. Validation of the new method: Approved by the Ethics Committee of Yijishan Hospital of Wannan Medical College. Adult patients who needed tracheal intubation under general anaesthesia for elective surgery were enrolled. The data of patients were input into the computer software to calculate the expected visibility of the glottis. The results of tracheal intubation were recorded by anaesthesiologists. The primary observation outcome was the screening performance of the expected visibility of the glottis for difficult tracheal intubation. RESULTS: The geometric model and software of the GADAS method were successfully developed and are available for use. We successfully observed 2068 patients, of whom 56 patients had difficult intubation. The area under the receiver operating characteristic curve of low expected glottis visibility for predicting difficult laryngoscopy was 0.96 (95% confidence interval [CI]: 0.95-0.96). The sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 94.3% (95% CI: 93.2%-95.3), respectively. CONCLUSIONS: It is feasible to screen difficult-airway patients by applying computer techniques to simulate geometric changes in the upper airway.

Vancomycin-induced elevation of liver enzyme levels in a 3-year-old boy with bacterial meningitis: A pediatric case report.

BACKGROUND: Vancomycin as a glycopeptide antibiotic agent plays a vital role in the treatment of gram-positive bacterial infections, especially methicillin-resistant Staphylococcus aureus. Vancomycin-induced liver disease is rarely reported previously; isolated cases have been reported only in adults and none in children except in a 3-month-old girl published in a Chinese journal. CASE SUMMARY: A 3-year-old boy received vancomycin for the treatment of bacterial meningitis for more than 3 weeks. The baseline liver enzyme levels of alanine aminotransferase (ALT) (12 U/L), aspartate aminotransferase (AST) (18 U/L), and gamma-glutamyl transferase (GGT) (26 U/L) were obtained after administering vancomycin for 2 days. Liver enzyme levels of ALT (191 U/L), AST (175 U/L), and GGT (92 U/L) were obviously elevated after administering vancomycin for 22 days; this elevation was reversed after vancomycin discontinuation. This case suggested that regular examination of liver function is necessary for all individuals who initiated vancomycin. PRACTICE IMPLICATIONS: This is a rarely known case of vancomycin-induced elevation of ALT and AST and the first reported case of vancomycin causing GGT elevation in children, which suggested that regular examination of liver function is required during the use of vancomycin in children and could help avoid progressive liver injury. This case adds to the limited number of reports on vancomycin-induced liver disease.

The cis-2-Dodecenoic Acid (BDSF) Quorum Sensing System in Burkholderia cenocepacia.

It has been demonstrated that quorum sensing (QS) is widely employed by bacterial cells to coordinately regulate various group behaviors. Diffusible signal factor (DSF)-type signals have emerged as a growing family of conserved cell-cell communication signals. In addition to the DSF signal initially identified in Xanthomonas campestris pv. campestris, Burkholderiadiffusible signal factor (BDSF) (cis-2-dodecenoic acid) has been recognized as a conserved DSF-type signal with specific characteristics in both signal perception and transduction from DSF signals. Here, we review the history and current progress of the research on this type of signal, especially focusing on its biosynthesis, signaling pathways, and biological functions. We also discuss and explore the huge potential of targeting this kind of QS system as a new therapeutic strategy to control bacterial infections and diseases.

The global disease burden of varicella-zoster virus infection from 1990 to 2019.

Data on the global epidemiology of varicella-zoster virus infection (VZVI) is limited. This study aimed to investigate the burden of VZVI based on the global burden of disease study 2019 data. The age-standardized rates, including the incidence, death, disability-adjusted life years (DALYs), and the estimated annual percentage changes (EAPC) of VZVI were calculated to evaluate the disease burden of VZVI. The global numbers of incident and death cases due to VZVI were 83 963 744 and 14 553, respectively. The age-standardized incidence rate of VZVI increased slightly all over the world, while the age-standardized death and DALYs rate decreased from 1990 to 2019 (EAPC = -2.31 and -1.61, respectively). The younger age (<5 years old) and older groups had the highest VZVI burden. The high sociodemographic index (SDI) region had the highest age-standardized incidence rates in 2019 (1236.28/100 000, 95% uncertainty interval [UI]: 1156.66-1335.50) and the low SDI region had the lowest incidence (1111.24/100 000, 95% UI: 1040.46-1209.55). The age-standardized death and DALYs rate of VZVI decreased with the increase of SDI. Amongst the 21 geographical regions, the high-income Asia-Pacific (1269.08/100 000) region had the highest age-standardized incidence rate in 2019, while Sub-Saharan Africa had the highest age-standardized death and DALYs rate. The global incidence of VZVI has continued to increase in the past 3 decades, while the age-standardized death and DALYs rates have decreased. More attention should be paid to the younger and older population, as well as low SDI regions.

The value of multiparameter combinations for predicting difficult airways by ultrasound.

BACKGROUND: Based on the upper airway anatomy and joint function parameters examined by ultrasound, a multiparameter ultrasound model for difficult airway assessment (ultrasound model) was established, and we evaluated its ability to predict difficult airways. METHODS: A prospective case-cohort study of difficult airway prediction in adult patients undergoing elective surgery with endotracheal intubation under general anesthesia, and ultrasound phantom examination for difficult airway assessment before anesthesia, including hyomental distance, tongue thickness, mandibular condylar mobility, mouth opening, thyromental distance, and modified Mallampati tests, was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of the ultrasound model and conventional airway assessment methods in predicting difficult airways. RESULTS: We successfully enrolled 1000 patients, including 51 with difficult laryngoscopy (DL) and 26 with difficult tracheal intubation (DTI). The area under the ROC curve (AUC) for the ultrasound model to predict DL was 0.84 (95% confidence interval [CI]: 0.82-0.87), and the sensitivity and specificity were 0.75 (95% CI: 0.60-0.86) and 0.82 (95% CI: 0.79-0.84), respectively. The AUC for predicting DTI was 0.89 (95% CI: 0.87-0.91), and the sensitivity and specificity were 0.85 (95% CI: 0.65-0.96) and 0.81 (95% CI: 0.78-0.83), respectively. Compared with mouth opening, thyromental distance, and modified Mallampati tests, the ultrasound model predicted a greater AUC for DL (P < 0.05). Compared with mouth opening and modified Mallampati tests, the ultrasound model predicted a greater AUC for DTI (P < 0.05). CONCLUSIONS: The ultrasound model has good predictive performance for difficult airways. TRIAL REGISTRATION: This study is registered on chictr.org.cn (ChiCTR-ROC-17013258); principal investigator: Jianling Xu; registration date: 06/11/2017).

Effect of individualized treatment strategy on postoperative nausea and vomiting in gynaecological laparoscopic surgery: a double-blind, randomized, controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) have always been a concern of clinicians and may increase medical costs for patients. Consensus guidelines recommend using multiple antiemetics with different mechanisms as prophylaxis in patients at high risk of PONV. Individualized risk scores for nausea and vomiting and individualized treatment strategies are feasible. This study evaluated the effect of individualized treatment strategies on postoperative nausea and vomiting after laparoscopic gynaecological operations. METHODS: This was a double-blind, randomized, controlled trial. A total of 119 adult patients who underwent gynaecological laparoscopic surgery under general anaesthesia were randomly divided into an individualized treatment group or a control group, with the individualized treatment group receiving individualized prevention according to a preoperative risk score of nausea and vomiting and the control group receiving no individualized prevention. Vomiting, retching, nausea, and use of rescue medication were all recorded for 24 h after the operation. The primary outcome variable was complete response, defined as no emesis or the use of rescue medication 24 h postoperatively. RESULTS: The complete response rate was higher in the individualized treatment group (56.7%) than in the control group (23.7%) (95% CI, 0.01-0.27; P < 0.001). The incidences of emesis (18.3% vs. 44.1%, P = 0.002) were significantly lower in the individualized treatment group than in the control group. There were no differences in any nausea (26.7% vs. 33.9%, P = 0.391) or rescue medication use (6.7% vs. 8.5%, P = 0.743). Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently in the individualized treatment group than in the control group. CONCLUSION: In conclusion, this single-centre, double-blind, randomized study suggests that an individualized PONV prophylactic treatment strategy based on the number of PONV risk factors could be a safe and effective regimen to reduce the incidence of PONV in adult patients undergoing laparoscopic gynaecological surgery.

Nomograms for predicting difficult airway based on ultrasound assessment.

BACKGROUND: Accurate prediction of the difficult airway (DA) could help to prevent catastrophic consequences in emergency resuscitation, intensive care, and general anesthesia. Until now, there is no nomogram prediction model for DA based on ultrasound assessment. In this study, we aimed to develop a predictive model for difficult tracheal intubation (DTI) and difficult laryngoscopy (DL) using nomogram based on ultrasound measurement. We hypothesized that nomogram could utilize multivariate data to predict DTI and DL. METHODS: A prospective observational DA study was designed. This study included 2254 patients underwent tracheal intubation. Common and airway ultrasound indicators were used for the prediction, including thyromental distance (TMD), modified Mallampati test (MMT) score, upper lip bite test (ULBT) score temporomandibular joint (TMJ) mobility and tongue thickness (TT). Univariate and the Akaike information criterion (AIC) stepwise logistic regression were used to identify independent predictors of DTI and DL. Nomograms were constructed to predict DL and DTL based on the AIC stepwise analysis results. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of the nomograms. RESULTS: Among the 2254 patients enrolled in this study, 142 (6.30%) patients had DL and 51 (2.26%) patients had DTI. After AIC stepwise analysis, ULBT, MMT, sex, TMJ, age, BMI, TMD, IID, and TT were integrated for DL nomogram; ULBT, TMJ, age, IID, TT were integrated for DTI nomogram. The areas under the ROC curves were 0.933 [95% confidence interval (CI), 0.912-0.954] and 0.974 (95% CI, 0.954-0.995) for DL and DTI, respectively. CONCLUSION: Nomograms based on airway ultrasonography could be a reliable tool in predicting DA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR-RCS-14004539 ), registered on 13th April 2014.

SAXS Examinations of the Redox-Dependent Formation of a DNA-SOD1 Complex.

Cu/Zn superoxide dismutase (SOD1) plays a key role in the maintenance of cellular reactive oxygen species (ROS) homeostasis as an antioxidant enzyme. We recently found that SOD1 is involved in the regulation of gene expression in response to changes in cellular ROS levels by binding to DNA-specific sequences. Moreover, the SOD1 binding to DNA was observed to be redox-dependent in solutions. Thus, we examined the redox-dependent DNA binding of SOD1 by multiple measurements, including small-angle X-ray scattering (SAXS), indicating the redox-dependent formation of a DNA-SOD1 complex in solutions. The redox-dependent formation of the DNA-SOD1 complex could underlie the SOD1 regulation of gene expression.

A new function of copper zinc superoxide dismutase: as a regulatory DNA-binding protein in gene expression in response to intracellular hydrogen peroxide.

In microorganisms, a number of metalloproteins including PerR are found to regulate gene expression in response to environmental reactive oxygen species (ROS) changes. However, discovery of similar regulatory mechanisms remains elusive within mammalian cells. As an antioxidant metalloenzyme that maintains intracellular ROS homeostasis, copper zinc superoxide dismutase (SOD1) has high affinity for DNA in solution and in cells. Here, we explored the regulatory roles of SOD1 in the expression of genes in response to ROS changes within mammalian cells. SOD1-occupied DNA sites with distinct sequence preference were identified. Changing ROS levels both were found to impact DNA-SOD1 interactions in solution and within HeLa cells. GGA was one of the base triplets that had direct contact with SOD1. DNA-SOD1 interactions were observed to regulate the ROS-responsive expression of functional genes including oncogenes and amyotrophic lateral sclerosis-linked genes in transcriptional phases. Our results confirm another function of SOD1, acting as a H2O2-responsive regulatory protein in the expression of numerous mammalian genes.

[A Project to Improve the Ability of Hemodialysis Staff to Respond to Fire Emergencies].

BACKGROUND & PROBLEMS: In case of fire in the hemodialysis room, it is necessary to help patients get away from dialysis machines smoothly and safely and evacuate the room rapidly. Our unit is located on a higher floor. An investigation showed that the accuracy rate for fire response awareness among the staffs in our unit was only 57.9%, while the accuracy rate of fire response skill operations was only 57.4%. Moreover, 62.0% of the staffs were not clear about the task grouping and task content of fire response. Confusion in our unit regarding the definition of patient mobility led to staffs classifying patients based on subjective perceptions and standards. Moreover, the unit also lacked an audit system for fire emergency operations and fire-response-related learning materials. PURPOSE: To improve staff knowledge and skills related to fire emergency response in the hemodialysis room to 100%. RESOLUTION: The project team worked out solutions such as adding a self-defense fire-fighting group to the dialysis information system, producing fire emergency response learning materials, establishing a seed personnel system, organizing on-the-job education, organizing fire response simulation drills, and implementing an audit system. RESULTS: The awareness of fire emergency response and the accuracy of skill operation among the staff were both improved to 100%, and there were statistically significant differences between the pre-test and post-test paired t-test results. Furthermore, consistent implementation of these resolution measures maintained the staff`s fire emergency response skills at 100% between June 2019 and May 2020. CONCLUSIONS: Tabletop simulation, practice drills, and skill operation audits are effective tools for improving the ability of staff in the hemodialysis room to respond to fire emergencies. It is recommended that institutions produce tabletop simulation props and combine regular on-site drills to improve the readiness of their staffs to respond to fire emergencies, which will shorten the response time during incidents.

The impact of hepatitis B virus infection status on the prevalence of nonalcoholic fatty liver disease: A population-based study.

BACKGROUND: We aimed to explore the impact of hepatitis B virus (HBV) infection on the prevalence of nonalcoholic fatty liver disease (NAFLD) based on clinical big data. METHODS: Data were collected from the health examination center of the First Affiliated Hospital of Fujian Medical University. Univariate and multivariate analysis were applied to investigate the relationship between HBV and NAFLD. RESULTS: A total of 14 452 patients were included, with an average age of 43.84 ± 13.03 years. Cases of HBV current infection, past infection, and noninfection were 21 102 110 (14.6%), 90 039 003 (62.3%), and 33 393 339 (23.1%), respectively. The prevalence of NAFLD was significantly lower in the current infection group (29.9%) than in the past infection group (35.8%) and noninfection group (31.9%) (P < .001). After adjusting for age, the prevalence of NAFLD in the current infection group remained the lowest across all of the age groups. Multivariate analysis showed that current infection was at a lower risk of NAFLD (odds ratio [OR] = 0.717, 95% CI: 0.608-0.846), whereas past infection had no effect on NAFLD. CONCLUSIONS: Current HBV infection may lower the risk of NAFLD. This effect becomes insignificant when the patient is no longer infected.

Comparison of MAFLD and NAFLD diagnostic criteria in real world.

BACKGROUND AND AIMS: Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020, the utility of which has not been tested and validated in real world. We aimed to compare the characteristics of MAFLD and non-alcoholic fatty liver disease (NAFLD). METHODS: The data was retrieved from the third National Health and Nutrition Examination Surveys of the United States, which is an unbiased survey dataset and frequently used for the study of fatty liver disease. RESULTS: A total of 13 083 cases with completed ultrasonography and laboratory data were identified from the NHANES III database. MAFLD was diagnosed in 4087/13 083 (31.24%) participants, while NAFLD in 4347/13 083 (33.23%) amongst the overall population and 4347/12 045 (36.09%) in patients without alcohol intake and other liver diseases. Compared with NAFLD, MAFLD patients were significantly older, had higher BMI level, higher proportions of metabolic comorbidities (diabetes, hypertension) and higher HOMA-IR, lipid and liver enzymes. MAFLD patients with alcohol consumption were younger than those without, and more likely to be male. They had less metabolic disorder but higher liver enzymes. There were more cases with advance fibrosis in MAFLD patients with alcohol consumption. CONCLUSION: MAFLD definition is more practical for identifying patients with fatty liver disease with high risk of disease progression.

Ternary Chalcogenides GeSb2Se3 and Ge3Sb4Se7 Containing a ∞1[Sb2Se2]2- 1D Chain and a 2D Structure Related to SnSe.

Ternary chalcogenides, GeSb2Se3 and Ge3Sb4Se7, were synthesized and characterized. These chalcogenides are the first ternary selenides in a ternary Ge-Sb-Se system that feature a layer structure related to black phosphorus and SnSe-type structures. Both compounds contain a ∞1[Sb2Se2]2- unit with Sb+ cations in a zigzag Sb-Sb chain structure, and Sb3+ cations in a distorted NaCl100-type of ∞1[Gen-2Sb2Sen]2+ unit (n = 4, 5). These materials exhibit n-type semiconducting properties with thermal conductivity significantly lower than that of GeSe and Sb2Se3, which could be correlated to the 1D Sb+ chain and disordered sites with different Ge/Sb compositions. It is anticipated that these newly discovered ternary chalcogenides may provide unique properties with enhanced thermoelectric properties.

Authors response to correspondence regarding paper entitled Syphilitic hepatitis: a case report and review of the literature.

In the correspondence from Abdurrahman et al., they raised three main concerns and critiques of our recently published article entitled "Syphilitic hepatitis: a case report and review of the literature". First question pertains to the timing of dermatology opinion, second regarding the history of sexual exposure, and lastly regarding the treatment duration of syphilitic hepatitis. We thank the authors for their constructive comments and would like to answer these questions in detail.

Association between NAFLD and risk of prevalent chronic kidney disease: why there is a difference between east and west?

BACKGROUNDS: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. METHODS: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. RESULTS: A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. CONCLUSION: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.