A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Objective To investigate the incidence,biochemical manifestations and genetic mutation features of glutaric acidemia type Ⅱ(GA-Ⅱ)in newborns in Quanzhou,Fujian province.Methods From January 2014 to December 2022,a total of 643 606 newborns were screened for inherited metabolic diseases by tandem mass spectrometry in the Quanzhou area.Suspected positive newborns with multiple acylcarnitine elevations were diagnosed by the MassARRAY assay and high-throughput sequencing technology.Results A total of 247 newborns showed multiple acylcarnitine elevations during the study period,and 19 newborns were diagnosed with GA-Ⅱ by genetic diagnosis.In addition,one newborn showed elevated levels of isovalerylcarnitine(C5),and was suspected to be isovaleric acidemia,which was confirmed with GA-Ⅱ by genetic diagnosis.Twenty newborns were eventually diagnosed with GA-Ⅱ,and the incidence of GA-Ⅱ in the study population was 1:32 180.Newborn screening results showed the concentrations of octanoylcarnitine(C8),decanoylcarnitine(C10)and dodecanylcarnitine(C12)were higher than the upper limit of the reference range,which were key indicators for screening GA-Ⅱ.Ten distinct electrontransfer flavoprotein dehydrogenase ETFDH gene mutations were found in patients with GA-Ⅱ,most of which were missense mutations.The most common ETFDH mutation was C.250G>A(p.A84T)with an allele frequency of 47.5％,followed by C.524G>A(R175H),C.998A>G(p.Y333C)and C.1657T>C(p.Y553H).Conclusion Newborn screening is an important approach for early detection of GA-Ⅱ,but patients with GA-Ⅱ may have atypical biochemical changes,and all newborns with abnormal newborn screening results should be subjected to high-throughput sequencing for genetic diagnosis.

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Apoptosis ; Autophagy ; Ferroptosis ; Iron/metabolism* ; Sequestosome-1 Protein/metabolism* ; Ubiquitin-Specific Proteases/metabolism*

A 56-year-old man presented with vague upper abdominal pain for more than 4 months. His abdominal ultrasound and MRI showed thickening of the neck and base of the gallbladder and nodule formation at the base of the gallbladder. 18F-FDG PET/CT revealed intense FDG uptake in the base of the gallbladder and multiple lymph nodes. 68Ga-FAPI-04 PET/CT not only showed intense FAPI uptake in the above mentioned FDG-avid lesions but also showed intense FAPI uptake in the neck lesion of the gallbladder and some other additional lymph nodes. Finally, histopathological examination confirmed poorly differentiated tubular adenocarcinoma of the neck and base of the gallbladder. Our case illustrated that 68Ga-FAPI-04 PET/CT may outperform 18F-FDG PET/CT in the detection of gallbladder cancer primary and metastatic lesions.

Objective:To understand the epidemiological characteristics and trends of syphilis in Kashgar area of Xinjiang Uygur Autonomous Region and provide a basis for formulating syphilis control measures.Methods:A descriptive epidemiological method was used to analyze the epidemiological characteristics of syphilis cases reported in Kashgar from 2005 to 2020, and the Joinpoint 4.8.0.1 software was used to calculate the annual percent change (APC) and perform trend testing.Results:From 2005 to 2020, 75 331 syphilis cases were reported in Kashgar. The number of syphilis cases increased from 720 in 2005 to 4 275 in 2020. The reported incidence increased from 19.57/100 000 in 2005 to 93.86/100 000 in 2020 in two stages. From 2005 to 2014, the reported incidence increased from 19.57/100 000 to 188.17/100 000, with an average annual increase of 28.24%. From 2014 to 2020, the reported incidence decreased from 188.17/100 000 to 93.86/100 000, with an average annual decrease of 12.58%. The reported incidence of primary syphilis, secondary syphilis, tertiary syphilis and fetal-transmitted syphilis increased first and then decreased with time. However, the reported incidence of recessive syphilis has been on the rise. Since 2018, the ratio of recessive syphilis has exceeded that of primary syphilis, becoming the main epidemic type. The incidence ratio of male to female was 0.97∶1 (37 097∶38 234); all age groups had reported cases, with 20-49-year-old group the most, accounting for 55.65% (41 921/75 331) of the total number of reported cases; occupational distribution was dominated by farmers, accounting for 71.15% (53 595/75 331) of all reported cases, and the proportion of farmers was increasing year by year, from 35.00% in 2005 to 79.04% in 2020.Conclusions:The situation of syphilis in Kashgar was serious in 2005-2020. We should strengthen the publicity of health knowledge and health education,especially strengthen the health education and prevention of young and middle-aged people, farmers, women of childbearing age and other key groups. Additional, the screening that raises syphilis ceaselessly even and detects level, accomplish early discovery, standard report and cure, in order to curb the popularity of syphilis.

Objective:To differentiate the methamphetamine users according to the developmental stages of addictive behavior, and explore the characteristics of different stages in order to provid a theoretical reference for our clinical intervention.Methods:Take the male methamphetamine users in compulsory detoxification institute whom were admitted from September 2018 to December 2019 as research objects.All the objects were asked to complete clinical diagnosis, interview and questionnaire evaluation in one week.According to the developmental stages of addictive behavior, the subjects were divided into occasional use group ( n=51), regular use group ( n=95) and compulsive use group ( n=157).All subjects were evaluated using visual analogue scale(VAS), Barrett impulsiveness scale(BIS)and CogState scale.SPSS 20.0 software was used for statistical analysis, AVOVA or Kruskal-Wallis H test was used for group comparison.Multiple Logistic regression analysis was used to explore the factors associated with the development of addictive behavior. Results:(1)The compulsive use group had higher cumulative duration(24(8, 48), 12(4, 24), 22(10, 36)), average dose(6.6±3.8, 2.8±1.4, 4.5±3.4) and craving score(1(0, 5), 0(0, 1), 1(0, 3)) than the other two groups(all P<0.05).And individuals in compulsive use group had more previous heroin use experience(20.4%, 9.8%, 14.8%, P<0.05).The regular use group had more withdrawal times than the other two groups(1(1, 3), 1(0, 1), 1(1, 2), P<0.05).The total scores of Barrett impulsiveness scale(42.8±13.3, 34.5±13.6, 36.1±14.9) and the scores in all dimensions in the compulsive use group were significantly higher than those in the other two groups(motor impulsiveness: 37.5±15.8, 27.8±13.4, 29.2±17.8; attentional impulsiveness: 43.2±18.0, 39.4±17.0, 37.2±18.1; non-planning impulsiveness: 47.2±19.8, 38.8±18.7, 40.7±20.8; P<0.05) .In the compulsive use users, the ISL(16.50±4.87, 19.30±4.78, 18.33±4.91) and SEC(0.76±0.21, 0.89±0.22, 0.81±0.21) scores about cognitive assessment were significantly lower than other two groups(both P<0.05).(2)The results of multiple Logistic regression analysis showed that cumulative duration ( β=0.022, OR=1.022, 95% CI: 1.003-1.042), dosage( β=0.625, OR=1.869, 95% CI: 1.196-2.921), craving ( β=0.194, OR=1.214, 95% CI: 1.002-1.215), the total scores of Barrett impulse scale( β=0.036, OR=1.037, 95% CI: 1.013-1.061), scores of non-planning impulsiveness( β=0.040, OR=1.041, 95% CI: 1.004-1.038), scores of motor impulsiveness( β=0.033, OR=1.214, 95% CI: 1.001-1.068) were associated with the periodic grouping of addictions. Conclusions:Addictive behavior is a progressive process and methamphetamine users at different stages have different characteristics in substance use, impulsiveness and cognitive function.The development of addictive behavior is associated with the time, dosage and craving of substance use, as well as the personality impulsivity of users.And the compulsive users suffered more cognitive impairment than the other two groups. The methamphetamine users should be identified dynamically and targeted therapeutic intervention measures should be carried out to block the addictive process to achieve the goal of harm reduction.

Objective:To study the characteristics of video electroencephalogram (VEEG) and cranial magnetic resonance imaging (MRI) in neonates with inborn errors of metabolism (IEM) and to determine the predictive value for prognostic.Method:From June 2016 to December 2018, a retrospective study was performed on newborns diagnosed with IEM receiving VEEG examinations at the Neonatology Department of our hospital. VEEG and cranial MRI were used as prognostic indicators and the follow-up results were used as criteria predicting the accuracy of prognosis. The accuracy of the prediction was calculated using a 4 × 4 table.Result:A total of 21 eligible cases with 14 types of IEM were included. The most common type of IEM was organic acidemia (47.6%, 10/21). 16 cases (76.2%) had abnormal VEEG background patterns, including 8 cases of organic acidemia, 3 cases of urea cycle disorders, 1 case of energy metabolism disorder and 4 cases of other IEMs. No significant differences existed in the abnormality rate of VEEG background patterns among these groups ( P=0.882). VEEG showed 3 cases of seizures including 2 cases of electrographic-only seizures. Interburst interval durations were shortened on VEEG background with the decrease of blood ammonia level. The positive predictive values of the moderate-to-severe abnormal VEEG background and the presence of major cerebral lesions on MRI in predicting poor prognosis were 90.0% (95% CI 55.5%~99.7%) and 100% (95% CI 66.4%~100%), respectively, and the negative predictive values were 50.0% (95% CI 18.7%~81.3%) and 85.7% (95% CI 42.1%~99.6%), respectively. Conclusion:Neonates with IEM have higher incidences of abnormal VEEG. Continuous VEEG may accurately diagnose neonatal seizures and effectively monitor brain function. VEEG is a useful tool monitoring infants with IEM and predicting adverse outcomes, especially when used in combination with brain MRI.

Objective:To systematically review the therapeutic effect of continuous high positive end-expiratory pressure (PEEP) ventilation in patients with non-acute lung injury/acute respiratory distress syndrome (non-ALI/ARDS) under general anesthesia mechanical ventilation in the intensive care unit (ICU).Methods:PubMed, JBI Evidence-based Nursing Center Library, Cochrane Library, Embase, Medline, Wanfang Date, CNKI and VIP Database were searched for randomized controlled trials (RCT) and clinical controlled trials (CCT) using different levels of PEEP for the treatment of patients (uncombined ALI/ARDS) in ICU. The search period was from January 1st, 1990 to November 30th, 2018. Compared with the control group, the experimental group was treated with relatively high levels of PEEP ventilation. Outcome indicators were hospital mortality or 28-day mortality, partial oxygen pressure, and incidence of ARDS, atelectasis, and lung infections, etc. The RevMan 5.3 software was used for Meta-analysis.Results:Twelve articles were included, all of which were RCT studies; with 2 Chinese articles and 10 English articles. Meta-analysis showd that there was no statistically significant difference in the effect of different levels of PEEP on the mortality of patients [hospital mortality: odds ratio ( OR) = 1.06, 95% confidence interval (95% CI) was 0.57 to 1.96, P = 0.85; 28-day mortality: OR = 0.34, 95% CI was 0.09 to 1.32, P = 0.12]. Compared with low PEEP, persistently high PEEP could increase the patient's partial oxygen pressure [weighted mean difference ( WMD) = 48.27, 95% CI was 22.56 to 73.97, P = 0.000 2], prevent the occurrence of ARDS ( OR = 0.32, 95% CI was 0.13 to 0.82, P = 0.02), and decrease the incidence of lung infection ( OR = 0.52, 95% CI was 0.30 to 0.89, P = 0.02), but there was no significant difference in the incidence of atelectasis between the two groups ( OR = 0.69, 95% CI was 0.23 to 2.06, P = 0.51). Conclusion:In the treatment of patients in ICU with non-ALI/ARDS under general anesthesia mechanical ventilation, using relatively high levels of PEEP (10-16 cmH 2O, 1 cmH 2O = 0.098 kPa) instead of low levels of PEEP (≤8 cmH 2O) can significantly increase the partial oxygen pressure and significantly reduce the incidences of ARDS and lung infection.