Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

Objective:To investigate the psychological status of HD nursing staff in hospitals in Guangdong province and its influential factors.Methods:1 630 nursing staff in HD rooms of 71 hospitals or units in Guangdong Province in February and March 2020 were evaluated by using the 10-item Kessler psychological distress scale (Kessler 10), General self-efficacy scale (GSES) and Connor-Davidson resilience scale (CD-RISC) to conduct a questionnaire survey on their psychological status. Insomnia severity index (ISI) and Fatigue scale-14 (FS-14) were used to investigate their degree of insomnia and fatigue. General information on gender, age, educational level, marital status, economic income, professional title, HD working hours, average weekly overtime times and hours, total number of HD patients per day, and whether holding other positions were collected.Results:A total of 1 630 questionnaires were collected, among which 1 629 were valid, with an effective recovery rate of 99.9%. The scores of the three scales were (20.16±7.47), (27.03±4.45) and (58.37±15.75), respectively. According to the Kessler 10, 835 people (51.2%) had mental disorders. Univariate analysis showed that age, educational level, economic income, type of work unit, total number of HD patients per day and living status in recent one week were related with Kessler 10 score (all P<0.05). Economic income, type of work unit, whether holding other positions, total number of HD patients per day and living status in recent one week were related with GSES scores (all P<0.05). Age, marital status, economic income, professional title, type of work unit, whether holding other positions and living status in recent one week were related to CD-RISC score (all P<0.05). Spearman rank correlation analysis showed that the number of HD machines ( r=0.100, P<0.001), the number of nurses ( r=0.082, P=0.001), average weekly overtime times ( r=0.142, P<0.001) and overtime hours ( r=0.136, P<0.001), ISI score ( r=0.572, P<0.001) and FS-14 score ( r=0.635, P<0.001) were correlated with Kessler 10 score. ISI score ( r=-0.311, P<0.001) and FS-14 score ( r=-0.335, P<0.001) were correlated with GSES score. Working years of HD service ( r=0.112, P<0.001), ISI score ( r=-0.289, P<0.001) and FS-14 score ( r=-0.314, P<0.001) were correlated with CD-RISC score. Multiple linear regression analysis showed that the economic income in 5 001-10 000 yuan (with<3 000 yuan as reference, B=-1.603, 95% CI -3.036--0.169, P=0.028) and the total number of HD patients per day >200 (with ≤50 as reference, B=-1.153, 95% CI -2.242--0.065, P=0.038) were negatively correlated with Kessler 10 score, and average weekly overtime times ( B=0.221, 95% CI 0.069-0.374, P=0.004), ISI score ( B=0.518, 95% CI 0.454-0.582, P<0.001) and FS-14 score ( B=1.166, 95% CI 1.066-1.265, P<0.001) were positively correlated with Kessler 10 score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=1.930, 95% CI 0.847-3.013, P<0.001), 5 001-10 000 yuan ( B=1.949, 95% CI 0.887-3.012, P<0.001), 10 001-15 000 yuan ( B=1.482, 95% CI 0.318-2.647, P=0.013), >20 000 yuan ( B=4.300, 95% CI 2.463-6.136, P<0.001), secondary hospital (with primary hospitals as reference, B= 1.078, 95% CI 0.005-2.152, P=0.049) and holding other positions ( B=0.729, 95% CI 0.277-1.181, P=0.002) were positively correlated with GSES score, and ISI score ( B=-0.169, 95% CI -0.217--0.120, P<0.001) and FS-14 score ( B=-0.403, 95% CI -0.478--0.328, P<0.001) were negatively correlated with GSES score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=7.631, 95% CI 3.753-11.509, P<0.001), 5 001-10 000 yuan ( B=9.236, 95% CI 5.362-13.110, P<0.001), 10 001-15 000 yuan ( B=9.039, 95% CI 4.735-13.342, P<0.001), 15 001-20 000 yuan ( B=8.639, 95% CI 2.989-14.289, P=0.003), >20 000 yuan ( B=16.101, 95% CI 9.162-23.039, P<0.001) and holding other positions ( B=3.228, 95% CI 1.510-4.945, P<0.001) were positively correlated with CD-RISC score, and ISI score ( B=-0.593, 95% CI -0.765--0.420, P<0.001) and FS-14 score ( B=-1.258, 95% CI -1.525--0.992, P<0.001) were negatively correlated with CD-RISC score. Conclusion:The psychological status of nursing staff in HD rooms of hospitals in Guangdong Province needs to be improved. Effective preventive measures should be taken to provide timely psychological support, counseling and intervention to nursing staff with psychological abnormalities, and encourage them to take the initiative to seek psychological counseling when necessary, so as to promote their physical and mental health.

This article reports a case diagnosed with a large placental chorioangioma during the mid-trimester of pregnancy. The condition of this case progressed rapidly, with complications of edema, severe anemia, and severe heart failure, presenting a critical condition. After multidisciplinary consultation and discussion, amniotic fluid reduction and intrauterine fetal blood transfusion were performed at 27 weeks and 1 day of gestation to alleviate maternal and fetal symptoms. An emergency cesarean section was performed due to placental abruption 25 h after the operation, delivering an extremely preterm infant. The infant was diagnosed with fetal/newborn alloimmune thrombocytopenia caused by positive anti-human leukocyte antigen (HLA) antibodies after ineffective multiple platelet transfusions within three days after birth. The infant's condition improved after the transfusion of platelets negative for anti-HLA antibodies. This case was complicated by multiple high-risk factors, with an extremely high risk of fetal and postnatal death. Successful rescue through multidisciplinary collaboration was achieved, and both mother and child recovered well after the operation. It suggests that in clinical practice, attention should be paid to large chorioangiomas, and regular monitoring of the chorioangioma and fetal intrauterine development is necessary. For fetuses and newborns with thrombocytopenia, especially those with ineffective platelet transfusions, the detection of platelet antibodies should be emphasized, and while considering anti-platelet specific antibodies, the role of HLA antibodies should also be considered.

The family readiness for discharge of premature infants in the Neonatal Intensive Care Unit (NICU) is an important index to evaluate the safe discharge of premature infants, and a good family discharge readiness is the basic guarantee for the smooth recovery and healthy growth of premature infants. This article summarizes the concept, influencing factors, and intervention strategies of family discharge readiness for premature infants in NICU, in order to provide reference for the formulation and improvement of discharge readiness measures for premature infants in NICU.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

AIM: To assess the bioequivalence of oral dexamethasone acetate tablets between the test and reference formulations in healthy adult Chinese subjects on an empty stomach and after meals. METHODS: A randomized, open, single-dose, two-cycle double crossover bioequivalence study was followed. Twenty-four healthy subjects were included in the fasting group, and 32 healthy subjects were included in the postprandial group, taking 2 tablets (0.75 mg/tablet) of the test formulation (T) or 3 tablets (0.50 mg/tablet) of the reference formulation (R) per cycle for two cycles. The concentrations of dexamethasone acetate in human plasma were determined using liquid chromatography-mass spectrometry, and the pharmacokinetic parameters were calculated according to the non-atrial model using WinNonlin 8.0 software.The bioequivalence of both the test formulation and the reference formulation was evaluated. RESULTS: The pharmacokinetic parameters after oral administration of dexamethasone acetate tablets in a fasted state in subjects with the reference formulation are as follows: Tmax 1.13 (0.50, 4.00) and 1.00 (0.50, 5.00) h, AUC0-t (72.25±21.55) and (69.23±17.76) ng · mL

Objective　To analyze the survival status and influencing factors among HIV/AIDS transmitted through homosexual contact from 2004 to 2022 in Nan'an District, Chongqing, China. Methods　HIV infected/AIDS patients transmitted through homosexual contact in Nan'an District, Chongqing from 2004 to 2022 were selected for analysis. The survival rate was calculated using the life table method, the median survival time was calculated using the Kaplan-Meier method, and the survival curve was plotted. The Cox regression model was performed to identify factors influencing survival. Results　A total of 3 110 subjects were included in the study, of which 1 199 individuals (38.55%) were transmitted through homosexual contact. The majority of patients were under 30 years old (694, 57.88%), unmarried (917, 76.48%), and had a higher education level of college or above (724, 60.38%), mainly belonging to the Han ethnicity (1 160, 96.75%). Students accounted for 10.43% of occupational status. The majority of patients were initially diagnosed with HIV (1 104, 92.08%), with 71.45% having a CD4+T lymphocyte count >350 cells/μL at the time of initial testing. The primary source of samples was from testing and consultation (52.88%), and the vast majority (93.16%) underwent antiviral treatment. The median survival time for patients transmitted through homosexual contact was 191.45 months, which was higher than 158.37 months of patients transmitted through other routes, demonstrating statistical significance (P<0.001). Multivariate analysis showed that among patients transmitted through homosexual contact, those with CD4+T lymphocyte count≤200 cells/μL had a higher risk of death compared to those with CD4+ T lymphocyte count>350 cells/μL. HIV infected/AIDS patients who did not receive antiviral treatment also had a higher risk of death. Conclusions　From 2004 to 2022, the reported incidence level of HIV/AIDS in Nan'an District showed an overall upward trend, with a slight decrease influenced by respiratory infectious diseases.The risk of death for individuals infected through same-sex transmission routes had not yet been found to be significantly lower than that of other transmission routes, which may be influenced by the late diagnosis time and short follow-up time of individuals infected through same-sex transmission routes.

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies