Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules,and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers. Methods In this study,210 different structural types of VOCs were selected from the VOCMM penetration enhancer database,and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2),cholesterol(CHL),and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control,Nootkatone,and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments,with three rats in each group.The donor pool solutions were 3%gastrodin,3%gas-trodin+3%nootkatone,and 3%gastrodin+3%3-butylidenephthalide,respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12,μg/cm2). Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA,and hydrogen bonded to the head group of CER2.Among them,sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings,benzene rings,and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis,most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09 μg/cm2,and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5 503.00±1 080.00 μg/cm2,P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98 μg/cm2,P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers,and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.

Objective:To evaluate the influence of Helicobacter pylori ( H. pylori) infection on anxiety and depression in patients with chronic gastritis. Methods:From December 1 2020 to June 30 2021, 387 patients with chronic gastritis who visited the outpatient Department of Gastroenterology, the First Hospital Affiliated to Air Force Medical University were continuously recruited. According to the status of current H. pylori infection, the patients were divided into H. pylori uninfected group and H. pylori infected group. The general demographic information of patients was collected. Hamilton anxiety scale, Hamilton depression rating scale-24, Pittsburgh sleep quality index (PSQI) and gastrointestinal symptom rating scale (GSRS) were filled in. The detection rates of anxiety and depression were compared between the H. pylori uninfected group and the H. pylori infected group according to demographic characteristics. Chi-square test and multiple logistic regression analysis were used for statistical analysis. Results:Finally, 360 patients with chronic gastritis were enrolled, including 200 patients in H. pylori uninfected group and 160 patients in H. pylori infected group. The detection rates of anxiety and depression of the H. pylori infected group were both higher than those of the H. pylori uninfected group (48.1%, 77/160 vs. 30.0%, 60/200; 25.0%, 40/160 vs. 12.5%, 25/200), and the differences were statistically significant ( χ2=12.39 and 9.39, P<0.001 and=0.002). The detection rate of anxiety of male patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (45.1%, 32/71 vs. 24.5%, 27/110); the detection rate of depression of female patients in the H. pylori infected group was higher than that in the H. pylori uninfected group (30.3%, 27/89 vs. 11.1%, 10/90), and the differences were statistically significant ( χ2=8.27 and 10.09, P=0.004 and 0.001). The detection rates of anxiety and depression of patients less than 48 years old in the H. pylori infected group were both higher than those in the H. pylori uninfected group (46.2%, 37/80 vs. 21.9%, 21/96; 20.0%, 16/80 vs. 7.3%, 7/96), and the differences were statistically significant ( χ2=11.73 and 6.20, P=0.001 and 0.013). The detection rates of anxiety and depression of the patients with high school education and below in the H. pylori infected group were higher than those in the H. pylori uninfected group (56.5%, 48/85 vs. 31.7%, 38/120; 32.9%, 28/85 vs. 14.2%, 17/120), and the differences were statistically significant ( χ2=12.57 and 10.24, P<0.001 and =0.001). The results of multivariate analysis showed that H. pylori infection, history of hypertension, PSQI score ≥8, GSRS score ≥7, chronic superficial gastritis and chronic atrophic gastritis were independent risk factors of anxiety in patients with chronic gastritis( P<0.001, =0.013, =0.001, <0.001, =0.036, =0.021), and the risk of anxiety of patients with H. pylori infection was 2.509 times as much as that in uninfected patients (95% confidence interval 1.512 to 4.163). H. pylori infection, PSQI score ≥8, GSRS score≥7, and having overnight dish ≥3 times per week all were independent risk factors of depression in patients with chronic gastritis( P=0.004, =0.002, <0.001, =0.001). The risk of depression in patients with H. pylori infection was 2.563 times as much as that in uninfected patients (95% confidence interval 1.356 to 4.846). Conclusion:H. pylori infection is correlated to anxiety and depression in patients with chronic gastritis, and it is an independent risk factor of anxiety and depression in patients with chronic gastritis.

Oxidative Phosphorylation ; Acetylglucosamine ; Uridine Diphosphate N-Acetylglucosamine/metabolism*

Objective:To investigate the anxiety and depression in patients with gallbladder polyps, gallbladder stones and post-cholecystectomy.Methods:From December 2020 to August 2021, consecutive patients who visited the Department of Gastroenterology, First Affiliated Hospital of Air Force Medical University, were enrolled and divided into normal gallbladder group, gallbladder polyp group, gallbladder stone group and post-cholecystectomy group, with 100 patients in each group. Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to evaluate patients′ anxiety or depression. Quality of life, sleep quality and severity of gastrointestinal symptom were assessed by short form 36 (SF-36), Pittsburgh sleep quality index (PSQI) scale and gastrointestinal symptom rating scale (GSRS) respectively. The incidence of anxiety or depression of patients in the 4 groups were compared, and the related risk factors of anxiety and depression were analyzed. Chi-square test and multiple logistic regression were used for statistical analysis.Results:Among 400 patients, 89 patients (22.2%) suffered from anxiety; and the incidences of anxiety of normal gallbladder group, gallbladder polyp group, gallbladder stone group and post-cholecystectomy group were 9.0% (9/100), 19.0% (19/100), 25.0% (25/100) and 36.0% (36/100) respectively. There was statistically significant difference in the incidence of anxiety among the 4 groups ( χ2=22.12, P<0.001). The incidence rates of anxiety of the gallbladder polyp group, gallbladder stone group and post-cholecystectomy group were all higher than that of the normal gallbladder group, and the differences were all statistically significant ( χ2=4.15, 9.07 and 20.90, P=0.042, 0.003 and <0.001). The incidence of anxiety of post-cholecystectomy group was higher than that of gallbladder polyp group, and the difference was statistically significant ( χ2=7.25, P=0.007). Among the 400 patients, 70 patients (17.5%) suffered from depression. The incidence rates of depression of the normal gallbladder group, gallbladder polyp group, gallbladder stone group and post-cholecystectomy group were 5.0% (5/100), 10.0% (10/100), 24.0% (24/100) and 31.0% (31/100) respectively. There was statistically significant difference in the incidence of depression among the 4 groups ( χ2=30.27, P<0.001). The incidences of depression of the gallbladder stone group and post-cholecystectomy group were both higher than that of the normal gallbladder group and gallbladder polyp group, and the differences were statistically significant ( χ2=14.56, 22.90, 6.94 and 13.53, P<0.001, <0.001, =0.008 and <0.001). The results of multivariate analysis showed that history of cholecystectomy, history of coronary heart disease, consumption of overnight food ≥3 times per week, PSQI score ≥ 8 and GSRS score ≥9 were independent risk factors for anxiety ( OR, 95%confidence interval: 4.02, 1.60 to 10.13; 10.01, 2.15 to 46.68; 4.15, 1.87 to 9.19; 4.69, 2.58 to 8.52; 3.02, 1.64 to 5.58; P=0.003, 0.003, <0.001, <0.001, and <0.001). Gallbladder stones history of cholecystectomy, consumption of overnight food ≥3 times per week, consumption of fresh fruit < 200 g/d, PSQI score ≥8 and GSRS score ≥9 were independent risk factors for depression ( OR, 95%confidence interval: 4.40, 1.38 to 14.06; 4.97, 1.54 to 16.12; 4.23, 1.61 to 11.08; 3.78, 1.32 to 10.85; 5.59, 2.78 to 11.27, 4.19, 1.94 to 9.04; P=0.012, 0.007, 0.003, 0.014, <0.001 and <0.001). Conclusions:The incidences of anxiety and depression in patients with gallbladder stones or post-cholecystectomy are higher than that of people with normal gallbladder. A history of cholecystectomy is the independent risk factor for anxiety and depression. Gallbladder stones is the independent risk factor of depression. Clinical attention should be paid to the mental state of patients with gallbladder polyps, gallbladder stones, especially post-cholecystectomy.

Background::High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori ( H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment. Methods::This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance. Results::A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (–9.19% in the ITT analysis, –9.21% in the MITT analysis, and –9.73% in the PP analysis) was greater than the predefined non-inferiority margin of –10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups. Conclusions::Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region. Trial registration::Clinicaltrials.gov, NCT04678492.

Objective:To investigate the changes of T lymphocyte subsets and cytokines in children with he-patitis B virus(HBV)-associated glomerulonephritis (HBV-GN), and their relationship with HBV-DNA load.Methods:Forty-one children who was the first diagnosed with HBV-GN in Department of Pediatrics, the People′s Hospital of Gansu Province and Institute of Infectious Diseases, the First Hospital of Lanzhou University from September 2012 to September 2016 were collected as the objects(HBV-GN group). At the same time, the 40 patients with HBV infection (chronic HBV infection, normal liver and kidney function, normal 24-hour proteinuria quantitation, no hematuria under the microscope, no recent symptoms of cold and fever, etc.) were enrolled as the control group.The levels of T lymphocyte subset, tumor necrosis factor α(TNF-α), interferon-γ (IFN-γ), interleukin (IL)-2, IL-4, IL-6, IL-8 and IL-10 in the HBV-GN group and the control group were compared, and the relationship between HBV-DNA and cell factors was farther analyzed.Results:Compared with the control group, the proportions of CD3 + T, CD4 + T lymphocyte and CD4 + /CD8 + ratio decreased in the HBV-GN group(0.632±0.052 vs.0.692±0.047, 0.204±0.050 vs.0.466±0.038, 0.006±0.002 vs.0.017±0.003, t=1.025, 3.342, 5.234, all P<0.05), and the proportions of CD8 + T lymphocyte was significantly higher than that in the control group (0.411±0.023 vs.0.220±0.043, t=4.452, P<0.01). Besides, IL-2 and IFN-γ levels in the HBV-GN group were significantly lower than those in the control group[(23.36±2.55) ng/L vs.(36.33±1.24) ng/L, (19.20±2.18) ng/L vs.(61.25±2.08) ng/L, all P<0.05], and the serum levels of TNF-α, IL-4, IL-6, IL-8, and IL-10 were significantly higher than those in the control group[(19.60±1.46) ng/L vs.( 6.68±2.32) ng/L, (13.65±3.34) ng/L vs.(1.35±1.52) ng/L, (5.57±1.02) ng/L vs.(1.43±0.57) ng/L, (26.32±3.45) ng/L vs.(9.68±2.55) ng/L, (19.82±2.78) ng/L vs.(1.02±0.56) ng/L, all P<0.01]. Moreover, in HBV-GN patients, there was negative correlation between HBV-DNA load and IFN-γ, IL-2( r=-0.985, -0.943, all P<0.05), and positive relationship in HBV-DNA load with TNF-α, IL-4, IL-6, IL-8 and IL -10 levels( r=0.942, 0.966, 0.953, 0.944, 0.963, all P<0.05). Conclusions:There is an CD4 + /CD8 + imbalance and an abnormal level of cell factors in HBV-GN progression.In further HBV-GN treatment, HBV-DNA and the cell factors should be detected simultaneously to dynamically eva-luate the illness change and the clinical curative effect.

Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.

Objective:To explore the effects of cognitive belief, acceptance and state anxiety on auditory hallucination symptom in patients with schizophrenia and its effect path.Methods:From October 2018 to July 2019, a total of 133 inpatients with schizophrenia who had auditory hallucinations in a ClassⅢ Grade A psychiatric hospital in Shanghai were selected as research objects by the convenience sampling. They were investigated by General Information Questionnaire, Psychotic Symptoms Rating Scales Auditory Hallucinations (PSYRATS-AH) , Beliefs About Voices Questionnaire-Revised (BAVQ-R) and State Anxiety Inventory of State-Trait Anxiety Inventory (S-AI) .Results:The PSYRATS-AH score in 133 patients was (23.15±8.06) and BAVQ-R score was (8.62±10.21) . Bad cognition was dominant in 75.2% (100/133) patients, goodwill cognition was dominant in 18.8% (25/133) patients and two cognitions were in a balanced state in 6.0% (8/133) patients. The S-AI score of 133 patients was (41.50±13.50) . 45.9% (61/133) patients had mild anxiety, 46.6% (62/133) had moderate anxiety and 7.5% (10/133) had severe anxiety. In terms of acceptance, 43.6% (58/133) of patients could not tolerate auditory hallucinations, 42.9% (57/133) barely tolerated auditory hallucinations and 13.5% (18/133) could tolerate auditory hallucinations. Multiple regression analysis showed that cognitive belief, acceptance, and state anxiety were factors that affected the severity of auditory hallucinations, explaining 56.0% of the total variation ( F=57.024, P<0.001) . Correlation analysis found that severity of auditory hallucination was positively correlated with cognitive belief and state anxiety ( P<0.01) , but significantly negatively correlated with acceptance ( P<0.01) . Path analysis found that cognitive belief had direct and indirect effects on severity of auditory hallucination while acceptance and state anxiety had direct effects on them. Conclusions:The severity of auditory hallucination in inpatients with schizophrenia is moderate or above. The cognitive belief, acceptance and state anxiety of patients are important factors affecting the severity of auditory hallucination.

Chuangxinmycin is an antibiotic isolated from CPCC 200056 in the 1970s with a novel indole-dihydrothiopyran heterocyclic skeleton. Chuangxinmycin showed antibacterial activity and efficacy in mouse infection models as well as preliminary clinical trials. But the biosynthetic pathway of chuangxinmycin has been obscure since its discovery. Herein, we report the identification of a stretch of DNA from the genome of CPCC 200056 that encodes genes for biosynthesis of chuangxinmycin by bioinformatics analysis. The designated cluster was then confirmed to be responsible for chuangxinmycin biosynthesis by direct cloning and heterologous expressing in M1146. The cytochrome P450 CxnD was verified to be involved in the dihydrothiopyran ring closure reaction by the identification of seco-chuangxinmycin in M1146 harboring the gene cluster with an inactivated . Based on these results, a plausible biosynthetic pathway for chuangxinmycin biosynthesis was proposed, by hijacking the primary sulfur transfer system for sulfur incorporation. The identification of the biosynthetic gene cluster of chuangxinmycin paves the way for elucidating the detail biochemical machinery for chuangxinmycin biosynthesis, and provides the basis for the generation of novel chuangxinmycin derivatives by means of combinatorial biosynthesis and synthetic biology.