In this study,the immunological characteristics of the PhoP protein were explored with a two-component system of Mycobacterium tuberculosis(Mtb).Bioinformatics was used to predict the B and T cell epitopes of the PhoP protein.A re-combinant expression plasmid was constructed by PCR analysis of the phoP sequence and cloning into the prokaryotic expres-sion vector pET-28a(+).Competent Escherichia coli BL21 cells were transformed with the recombinant plasmid and expres-sion was induced with IPTG.The recombinant PhoP protein was purified by affinity chromatography.Serum levels of PhoP-specific antibodies in Mtb-infected mice and tuberculosis(TB)patients were analyzed with an ELISA.BALB/c mice were im-munized with the PhoP recombinant protein by intramuscular injection.Sera of mice were collected and antibody titers were detected with an ELISA and specificity was assessed by West-ern blot analysis.Mouse splenocytes were isolated and the pro-portions of IFN-y-positive cells and cytokine levels were detec-ted with an ELISpot and ELISA,respectively.Bioinformatics i-dentified 24 B cell and 11 T cell epitopes of the PhoP protein.A prokaryotic recombinant vector of PhoP was successfully con-structed and the recombinant PhoP protein was obtained by purification.Specific antibody levels to PhoP in sera of Mtb in-fected mice and TB patients increased significantly,with preci-sion of 99.9％and 82.5％,and specificity of 100％,respectively.PhoP protein immunization successfully induced production of specific antibodies in mice.Stimulated by antigens in vitro,IL-2 and IFN-γ levels were significantly increased in the splenocytes of immunized mice.Immunization with the PhoP protein induce a humoral immune response and Thl-dominated cellular immu-nity,indicating that the PhoP protein was immunogenic with diagnostic efficacy for TB.These results lay a foundation to clari-fy the role of PhoP in Mtb infection and application for diagnosis and prevention of TB.

Objective:To investigate the clinicopathological factors affecting the long-term survival of patients with duodenal papillary carcinoma (DPC) after pancreaticoduodenectomy (PD).Methods:The clinicopathological and follow-up data of patients with DPC who underwent PD at the First Affiliated Hospital of Anhui Medical University and the Second Hospital of Anhui Medical University from Jan 2015 to Dec 2021 were retrospectively analyzed.Results:All 73 cases have been followed-up. The median follow-up time was 60 months. Multivariate analysis of COX proportional risk model showed that positive lymph node metastasis and tumor size over 2.5 cm were common independent risk factors for OS and DFS. Lymph node metastasis was confirmed pathologically in 20 patients. Multivariate analysis results of Logistic regression model showed that smoking, tumor breaking through the serous layer and tumor low differentiation were independent risk factors for lymph node metastasis.Conclusions:Poor prognosis was associated with tumors that were larger than 2.5 cm, and with lymph node metastases. Preoperative smoking history, tumor breaking through the serous layer and low tumor differentiation were the predictors of positive lymph node metastasis.

Objective To understand the status of screen exposure in children with epilepsy and analyze the influencing factors for screen exposure time,providing a scientific basis for managing screen exposure in these children. Methods A convenience sampling method was used to select 275 children with epilepsy from outpatient clinics or those undergoing 24-hour electroencephalogram monitoring at two tertiary hospitals in Jinan from March to June 2023. Their parents (fathers or mothers) completed a questionnaire to collect data on screen exposure,parental screen regulation behaviors,and related information about the children and their families. The Wilcoxon rank-sum test or the Kruskal-Wallis H test was used to conduct a univariate analysis of the average screen exposure time of children on school days and weekends,as well as the daily average screen exposure time. A multivariate logistic regression analysis was used to identify the risk factors for children whose screen exposure time exceeded the recommended guidelines (average screen exposure time on school days>1 hour or average on weekends>2 hours). Results The median screen exposure duration on school days was 40 minutes,while on weekends it was 120 minutes. Among the children studied,23.1％ (63/273) had average screen exposure time exceeding 1 hour on school days,and 42.5％ (117/275) had average screen exposure time exceeding 2 hours on weekends. Four children experienced seizures while using screen devices. Multivariate logistic regression analysis indicated that using screen devices shortly before sleep,lower educational levels of parents,caregivers discussing screen content with children,and longer seizure durations in children were risk factors for exceeding recommended guidelines (P<0.05). Conclusions Some children with epilepsy have a screen exposure time exceeding the recommended guidelines. A longer seizure duration,lower parental education levels,and permissive digital parenting are closely associated with children's screen exposure time exceeding the recommended guidelines. Families and children exhibiting these characteristics should be prioritized for attention and health education.

Objective:To understand the clinical characteristics of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with renal injury after antiviral therapy in Henan Province, and to explore the risk factors of renal injury.Methods:A cross-sectional study was conducted to investigate HIV infection/AIDS patients receiving antiviral therapy in Zhengzhou Sixth People′s Hospital, Anyang Fifth People′s Hospital, Hebi Third People′s Hospital, Luo Yang Zhoushan Hospital and Lankao Central Hospital in Henan Province from April 1 to September 30, 2023. The clinical information including basic data, antiviral therapy regimens and comorbidities, and laboratory test results (blood urea nitrogen, serum creatinine, blood uric acid, urine routine, urine microalbumin, urine α 1-microglobulin (α 1-MG), urine β 2-microglobulin (β 2-MG), urine retinol binding protein (RBP), urine creatinine, HIV viral load, CD4 + T lymphocyte count) were collected. Multivariate binary logistic regression was used to analyze independent risk factors for renal injury. Results:A total of 2 526 HIV infection/AIDS patients were included, with the age of (45.52±14.28) years and 2 156 (85.4%) males. The main route of transmission was sexual transmission (91.6%, 2 314/2 526). The duration of antiviral therapy was 5.00(2.92, 8.00) years. Tenofovir (TDF)+ lamivudine (3TC)+ non-nucleoside reverse transcriptase inhibitors (NNRTI) accounted for 55.3%(1 396/2 526) of the current antiviral therapy regimen. The percentage of HIV viral load <50 copies/mL was 93.0%(2 350/2 526). The CD4 + T lymphocyte count was 476(337, 645)/μL. There were 156 patients (6.2%) complicated with hepatitis B and/or hepatitis C, 205 patients (8.1%) with diabetes, 379 patients (15.0%) with hyperlipidemia, and 189 patients (7.5%) with hyperuricemia. A total of 1 040 patients (41.2%) with renal injury were found through renal function test, including 355 cases (14.1%) with estimated glomerular filtration rate (eGFR) <60 mL/(min·1.73 m 2) or urine protein positive or urine albumin creatine ratio (UACR) ≥30 mg/g, 682 patients (27.0%) with pure tubular injury presented with only positive for urinary α 1-MG, urinary β 2-MG, or urinary RBP. eGFR< 60 mL/(min·1.73 m 2) was found in 71 cases (2.8%), eGFR from 60 to 89 mL/(min·1.73 m 2) was found in 509 cases (20.2%), and eGFR≥90 mL/(min·1.73 m 2) was found in 1 946 cases (77.0%). A total of 138 patients (5.5%) were identified as having combined chronic kidney disease (CKD). Among them, 110 patients (79.7%) were in CKD stages 1 to 2, and 117 patients (84.8%) were in urinary albumin A2 grade. Multivariate analysis of 355 patients with renal injury who had eGFR<60 mL/(min·1.73 m 2) or positive urine protein in urine routine or UACR ≥30 mg/g showed that ages of 50 to 69 years old (odds ratio( OR)=2.189, 95% confidence interval ( CI) 1.333 to 3.596, P=0.002)), ≥70 years old ( OR=5.190, 95% CI 2.912 to 9.248, P<0.001), female ( OR=1.685, 95% CI 1.241 to 2.286, P=0.001), combined opportunistic infection ( OR=2.521, 95% CI 1.567 to 4.056, P<0.001), combined hepatitis B ( OR=1.962, 95% CI 1.110 to 3.467, P=0.020), combined hepatitis C ( OR=1.883, 95% CI 1.043 to 3.400, P=0.036), combined diabetes ( OR=2.703, 95% CI 1.911 to 3.821, P<0.001), using TDF for two to four years ( OR=1.674, 95% CI 1.103 to 2.459, P=0.015), using TDF for greater than or equal to five years ( OR=1.880, 95% CI 1.287 to 2.746, P=0.001), using TDF combined with lopinavir/ritonavir (LPV/r) ( OR=3.610, 95% CI 2.273 to 5.734, P<0.001) and using TDF combined with non-LPV/r ( OR=1.495, 95% CI 1.036 to 2.157, P=0.031) were the risk factors of renal injury. Conclusions:There is a high proportion of renal injury among HIV infection/AIDS patients after antiviral therapy in Henan Province, including CKD and simple renal tubular injury. Older age, female, comorbidities, and long-term use of TDF are risk factors for renal injury.

Objective To observe the effect of omeprazole enteric-coated capsules on clinical symptoms and serum inflammatory factor levels in children with chronic gastritis and peptic ulcer.Methods Children with chronic gastritis and peptic ulcer were divided into treatment group and control group by random number table method.The control group was given triple therapy of ranitidine hydrochloride tablets,amoxicillin and clarithromycin,while the treatment group was treated with omeprazole enteric-coated capsules combined with amoxicillin and clarithromycin.Clinical efficacy,symptom relief time,and changes in serum motilin(MOT),gastrin(GAS)and inflammatory factors[interlrukin-6(IL-6)and interlrukin-8(IL-8)]were compared between the two groups.Results There were 48 cases in treatment group and 48 cases in control group.After treatment,the total effective rates in treatment group and control group were 93.74％(45 cases/48 cases)and 85.42％(41 cases/48 cases),with significant difference(P＜0.05).After treatment,the disappearance time of ulcer induced pain in treatment group and control group were(1.51±0.26)and(2.08±0.42)d;the disappearance time of acid regurgitation were(2.29±0.40)and(2.93±0.33)d;the disappearance time of burning sensation were(2.37±0.21)and(2.85±0.54)d;the length of hospital stay were(6.21±1.07)and(6.94±1.25)d;serum MOT levels were(298.48±35.15)and(273.58±31.25)pg·mL-1;serum GAS levels were(167.28±19.46)and(128.32±18.61)ng·L-1;IL-6 levels were(58.67±5.39)and(76.14±6.63)mg·mL-1;IL-8 levels were(50.08±5.16)and(58.68±5.49)mg·mL-1.The above indexes were significantly different between control group and treatment group(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 8.33％and 12.50％,with no statistical significance(P＞0.05).Conclusion Omeprazole enteric-coated capsules in the treatment of children with chronic gastritis and peptic ulcer can effectively alleviate various clinical symptoms and improve clinical efficacy.At the same time,it can lower serum levels of inflammatory factors and improve inflammation,with good effect.

Objective This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression (n = 113,154) and MDD (n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.

Objective: To observe the effects of Danggui Shaoyao powder (DSP) on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor (PPARγ)-liver X receptor (LXRα)-adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) pathway regulation. Methods: Eight C57BL/6J male mice were selected as the control group, and 24 ApoE−/− male mice were randomly divided into the atherosclerosis model (AS) group, atorvastatin calcium (AC) group, and DSP group (n = 8 each group). To establish an AS model, ApoE−/− mice were fed a high-fat diet for 16 weeks. Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining. Triglyceride (TG), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were determined in the livers using a single-reagent GPO-PAP method. Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver. Results: After 16 weeks of a high-fat diet, ApoE−/− mice showed more Oil Red O staining in the aorta and liver compared to the CONT group. Compared to the AS group, the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees. Furthermore, DSP significantly reduced the hepatic lipid area in ApoE−/− mice (P < .001) and decreased the levels of TG, TC, and LDL-C in liver (P < .001, P = .027, P < .001, respectively). DSP also significantly increased the levels of PPARγ, LXRα, ABCA1, and ABCG1 mRNA expression, as well as the PPARγ, LXRα, ABCA1, and ABCG1 protein expression in liver. Conclusion DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Sucrose synthase plays a crucial role in the plant sugar metabolism pathway by catalyzing the production of uridine diphosphate (UDP)-glucose, which serves as a bioactive glycosyl donor for various metabolic processes. In this study, a sucrose synthase gene named CtSus was cloned from Cistanche tubulosa, a traditional Chinese medicine known for its rich content of diverse glycosides, based on transcriptome analysis results. The open reading frame of CtSus was 2 418 bp long encoding 805 amino acids. Sequence analysis revealed conserved domains associated with the plant sucrose synthase family at both the N-terminal and C-terminal regions of CtSus protein. Phylogenetic analysis demonstrated that CtSus shares a close evolutionary relationship with sucrose synthases from other plants within the same order. Functional identification of CtSus was performed through whole-cell catalysis coupling with UGT71BD1, a characterized glycosyltransferase enzyme. The results showed that the introduction of CtSus significantly enhanced the conversion rate of glycosylation catalyzed by UGT71BD1. The soluble expression of CtSus in Escherichia coli was further achieved using the pCold^TM TF expression vector. In vitro enzymatic assay indicated the activity of CtSus to catalyze the formation of UDP-glucose in the presence of sucrose and UDP. Real-time quantitative-polymerase chain reaction results showed that the expression patterns of CtSus gene in different parts of C. tubulosa and the suspension cell cultures of C. tubulosa under drought stress correlated with the accumulation patterns observed for phenylethanol glycosides, respectively. Furthermore, key amino acids and their interactions between enzyme and substrate were explored based on protein structure prediction and molecular docking results. Overall, our findings identify a sucrose synthase CtSus responsible for the supply of the active glycosyl donor UDP-glucose during the biosynthesis of glycoside products in C. tubulosa and have also provided a gene element that can be utilized in engineering strain construction for glycoside products production.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.