Tropane alkaloids (TAs) are a class of anticholinergic drugs widely used in clinical practice and mainly extracted from plant, among which Atopa belladonna is the main commercial drug source. It is of great industrial value to obtain TAs in large quantities by plant metabolic engineering. In TAs pathway, cytochrome oxidase CYP82M3 catalyze the synthesis of tropinone and then tropinone reductase I (TRI) compete with TRII for tropinone to form tropine leading to the TAs synthesis (drainage). In this study, based on the "increasing flow and drainage" metabolic engineering strategy, two genes, namely HnCYP82M3 and DsTRI from Hyoscyamus niger and Datura stramonium, respectively, were overexpressed in the hair roots of A. belladonna, with a view to promote the TAs accumulation. The HnCYP82M3 gene was cloned from the root of H. niger, and it encoded amino acid with 91.7% sequence identity with AbCYP82M3 from A. belladonna. Overexpression of HnCYP82M3 alone did not affect the content of TAs in hair roots of A. belladonna, indicating that CYP82M3 was not a key enzyme in TAs biosynthesis. Simultaneous overexpression of HnCYP82M3 and DsTRI greatly promoted the accumulation of the three TAs, and the contents of hyoscyamine, anisodamine and scopolamine were 4.97 times, 2.83 times and 2.19 times that of the control, respectively, and the increase amplitude was greater than that of single overexpression of DsTRI. This study showed that the "increasing flow and drainage" strategy of enzyme genes co-expression at branch points was a promising metabolic engineering method to effectively improve the biosynthesis of TAs in A. belladonna, and laid a theoretical and technical foundation for the large-scale industrial acquisition of TAs.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Perihilar cholangiocarcinoma(PHC)is a common malignancy of biliary tract,for which surgery is the most effective treatment.However,its prognosis is not satisfactory even after surgical resection.In recent years,there have been some new advances in the surgical treatment of PHC.In this paper,we reviewed the existing literatures,demonstrated the current situation of preoperative biliary drainage,liver hyperplasia,hepatic resection,liver transplantation and minimally invasive surgery in the treatment of PHC,and prospected the future research direction.

Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To explore the clinical characteristics and predictive factors for plastic bronchitis (PB) in children with severe Mycoplasma pneumoniae pneumonia (SMPP). Methods:A retrospective cohort enrolled children with a clinical diagnosis of SMPP who were treated at the Department of Respiratory Medicine of Tianjin Children′s Hospital Machang District from January 1, 2018, to October 31, 2023. According to the bronchoscopy and pathological examination results, the patients were divided into 142 cases in the PB group and 274 cases in the non-PB group. The clinical manifestations, laboratory data, imaging findings, and treatments were analyzed.Mann-Whitney U test and Chi-square test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the risk factors. The receiver operating characteristic (ROC) curve was used to explore the predictive value of PB in SMPP. Results:Among 416 SMPP children, there were 197 males and 219 females; PB group 142 cases, non-PB group 274 cases, the age of disease onset was (6.9±2.9) years and (6.6±2.8) years in the PB group and the non-PB group respectively. The incidence of wheezing symptoms, hypoxemia, heat peak >40 ℃, the duration of fever, neutrophil-lymphocyte ratio, mean platelet volume, C-reactive protein, procalcitonin, interleukin-6, alanine transaminase, aspartate aminotransferase and ferritin were higher in the PB group (16 cases (11.3%) vs. 15 cases (5.5%), 14 cases (9.9%) vs. 12 cases (4.4%), 57 cases (40.1%) vs. 67 cases (24.5%), 10 (8, 12) vs. 9 (8, 12) d, 6.1 (4.1, 13.1)×10 9vs. 5.0 (3.7, 6.8)×10 9/L, 10.2 (9.6, 10.8) vs. 9.4 (8.9, 10.1) fl, 33.4 (16.0, 67.5) vs. 23.0 (10.4, 56.1) mg/L, 0.24 (0.12, 0.48) vs. 0.16 (0.09, 0.31) &mu;g/L, 39.9 (25.1, 81.4) vs. 31.3 (18.3, 59.3) ng/L, 16.0 (12.0, 29.0) vs. 14.0 (10.0, 24.3) U/L, 38.5 (28.0, 52.5) vs. 33.0 (25.0, 44.0) U/L, 233 (136, 488) vs. 156 (110, 293) &mu;g/L, χ2=4.55, 4.79, 11.00, Z=2.25, 4.00, 6.64, 2.76, 2.98, 3.09, 2.22, 2.62, 4.18, all P<0.05). Multivariate Logistic regression analysis showed that the dyspnea ( OR=2.97, 95% CI 1.35-6.55, P=0.007), the diminution of respiration ( OR=2.40, 95% CI 1.27-4.52, P=0.006), neutrophil-lymphocyte ratio (NLR) ( OR=2.07, 95% CI 1.71-2.51, P<0.001), lactate dehydrogenase (LDH) ( OR=1.01, 95% CI 1.00-1.01, P<0.001), mean platelet volume/platelet count (MPV/PLT) ( OR=1.39, 95% CI 1.13-1.71, P=0.002), pleural effusion ( OR=2.23, 95% CI 1.21-4.13, P=0.011),≥2/3 lobe consolidation ( OR=1.84, 95% CI 1.04-3.00, P=0.039) and atelectasis ( OR=1.98, 95% CI 1.02-3.48, P=0.044) were independent predictors of PB in children with SMPP. ROC curve analysis showed that the cut-off values for NLR, LDH and MPV/PLT in the diagnosis of PB were 2.79 (sensitivity 0.89, specificity 0.69, area under the curve (AUC)=0.86, P<0.001), 474 U/L (sensitivity 0.63, specificity 0.65, AUC=0.70, P=0.003) and 0.04 (sensitivity 0.75, specificity 0.53, AUC=0.68, P=0.005) respectively. Children in the PB group had longer hospital stays and corticosteroid treatment course than those in the non-PB group, the proportion of children in the PB group who received bronchoscopy treatment twice or more was higher (9 (8, 12) vs. 8 (6, 10) d, 7 (5, 8) vs. 6 (5, 7) d, 128 cases (90.1%) vs. 218 cases (79.6%), 106 cases (74.7%) vs. 54 cases (19.7%), Z=6.70, 5.06, χ2=7.48, 119.27, all P<0.05). Conclusions:The dyspnea, respiration diminution, NLR level elevation (>2.79) and pleural effusion were predictive factors for PB in children with SMPP. This provides a basis for the early identification of PB in children with SMPP.

Objective:To explore the value of circ_0054633 in early diagnosis and prognosis prediction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children with severe pneumonia.Methods:A retrospective case-control study was conducted on children with diagnosed severe pneumonia admitted to Tianjin Children's Hospital from July 1, 2022, to February 29, 2024. The clinical data was collected by electronic medical record system and clinical follow-up, including gender, age, lung injury prediction score (LIPS), pediatric critical illness score (PCIS), serum circ_0054633, interleukin-6 (IL-6), the indicators of the arterial blood-gas analysis, oxygenation index (PaO 2/FiO 2) within 24 hours of admission and the survival status of 28 days. According to whether ALI/ARDS occurred, they were divided into the ALI/ARDS group and the non-ALI/ARDS group. The differences of clinical data between the two groups were compared, and multivariate Logistic regression was used to analyze the risk factors for ALI/ARDS in children with severe pneumonia. The receiver operator characteristic curve (ROC curve) will be used to explore the early diagnostic value of ALI/ARDS in children with severe pneumonia. The patients of ALI/ARDS were divided into mild group, moderate group and severe group according to the level of PaO 2/FiO 2. The levels of serum circ_0054633 and IL-6 in various severity ALI/ARDS were compared. The differences of serum circ_0054633, IL-6 levels, PCIS score and LIPS score were compared between the two groups of ALI/ARDS patients according to different prognoses in 28 days, as well as the correlation between various risk factors and circ_0054633. Results:A total 74 children with severe pneumonia were included, with 34 cases in the ALI/ARDS group and 40 cases in the non-ALI/ARDS group. In ALI/ARDS group, there were 9 cases in the mild group, 15 cases in the moderate group and 10 cases in the severe group; while 12 cases died and 22 cases survived after 28 days. The serum circ_0054633, IL-6 level and LIPS score were higher in the ALI/ARDS group than the non-ALI/ARDS group, while the PCIS score was lower, and the two groups had significant difference. Multivariate Logistic regression analysis showed that circ_0054633 was independent predictors of ALI/ARDS in children with severe pneumonia [odds ratio ( OR) = 3.853, 95% confidence interval (95% CI) was 1.912-7.805, P = 0.017]. ROC curve analysis showed that the cut-off values for circ_0054633 in the diagnosis of ALI/ARDS were 3.955, sensitivity was 79.4%, specificity was 92.5%, area under the ROC curve (AUC) was 0.892. The serum circ_0054633 and IL-6 levels were higher in the children who died in 28 days than the children who were survived, while the PCIS score was lower, and the two groups had significant difference. Spearman correlation analysis showed that the level of circ_0054633 in children with ALI/ARDS was positively correlated with 28-day mortality and IL-6 ( r value was 0.675, 0.763, respectively, all P < 0.001), but negatively correlated with PCIS score ( r = -0.626, P < 0.001), while no significant correlation with LIPS score ( r = 0.389, P = 0.023). Conclusion:The level of serum circ_0054633 has a better value in early diagnosis and prognosis prediction of ALI/ARDS caused in children with severe pneumonia.

Objectives:To evaluate the association between estimated pulse wave velocity(ePWV)and risk of new-onset diabetes. Methods:A total of 82 440 employees without prior diabetes who participated in the health examination from July 2006 to October 2007 were selected as the observation cohort,participants were followed-up for a mean of(13.19±3.73)years.The study population was divided into four groups according to the ePWV quartiles:group Q1(ePWV<12.35 m/s,n=20 610),group Q2(12.35 m/s≤ePWV<13.74 m/s,n=20 610),group Q3(13.74 m/s≤ePWV<15.16 m/s,n=20 611),and group Q4(ePWV≥15.16 m/s,n=20 609).ROC curve was used to analyze the predictive value of ePWV for new-onset diabetes.The incidence density of diabetes in each group was calculated.After adjustment for the traditional cardiovascular risk factors(including sex,smoking,drinking,exercise,education level,family history of cardiovascular disease,history of myocardial infarction,history of stroke,body mass index,total cholesterol,fasting blood glucose,uric acid and high-sensitivity C-reactive protein),multivariate Cox regression models were used to evaluate the association between ePWV and risk of new-onset diabetes. Results:The area under the ROC curve of ePWV was 0.60 in the prediction of new-onset diabetes,and the optimal cut-offvalue was 12.78 m/s.With the increase of ePWV quartile,the incidence density of diabetes showed an increasing trend,which was 5.84/1 000 person years,12.04/1 000 person years,15.70/1 000 person years and 16.87/1 000 person years,respectively.After adjusting for the traditional cardiovascular risk factors,the risk of new onset diabetes increased by 9%(HR=1.09,95%CI:1.08-1.11,P<0.01)for each 1 m/s increase in ePWV.Subgroup analysis showed that higher ePWV was significantly associated with increased risk of new-onset diabetes regardless of presence or absence of cardiovascular risk factors,male or female,and age<51 years or age≥51 years,with the HR(95%CI)values of 1.07(1.05-1.08)and 1.21(1.08-1.36),1.07(1.06-1.09)and 1.17(1.15-1.20),1.22(1.19-1.24)and 1.06(1.04-1.07). Conclusions:ePWV has a certain predictive value for new-onset diabetes and is an independent risk factor for new-onset diabetes.

OBJECTIVE: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. METHODS: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. CONCLUSION The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
Humans ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV-1/genetics* ; Cross-Sectional Studies ; Phylogeny ; Anti-HIV Agents/therapeutic use* ; Drug Resistance, Viral/genetics* ; HIV Infections/epidemiology* ; Mutation ; China/epidemiology* ; Prevalence ; Genotype

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.