ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Aim To investigate the regulatory effect of geraniol on Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion(I/R)in rats. Methods In this experiment,all the male SD rats were randomly divided into nine groups receiving the following treatments:sham operation(sham); sham operation+200 mg·kg-1 geraniol; I/R; I/R+50 mg·kg-1 geraniol; I/R+100 mg/kg geraniol; I/R+200 mg·kg-1 geraniol; edaravone; I/R+ brusatol(Nrf2 inhibitor); I/R+200mg·kg-1 geraniol+brusatol. All rats received intraperitoneal injection of geraniol for five consecutive days before MCAO and again after MCAO. During the construction of cerebral I/R injury models,the blood vessels were isolated without any suture in the sham operation and the sham operation +200 mg·kg-1 geraniol groups while the blood vessels with suture in other groups. The damage of neurological function was evaluated by the modified rating scale for neurological function. The TTC,HE and Tunel staining methods were used to determine the cerebral infarction volume,the damage of the ischemic cortex and the apoptosis of cortical cells,respectively. The oxidative stress-related parameters then were measured. The protein expressions of Nrf2 and HO-1 were detected by immunohistochemical staining and the target protein expressions of the injured cortex were detected by Western blot. Results Compared with the model group,it was found that the geraniol treatment significantly repaired neural injury,reduced cerebral infarction volume,cerebral cortex damage and cell apoptosis. Meanwhile,geraniol intervention could significantly increase the expression of Nrf2/HO-1 protein in the right-sided cortex and reduce oxidative stress level. Conclusion Geraniol can attenuate cerebral injury induced by ischemia-reperfusion in rats via activating Nrf2/HO-1 signaling pathway.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Objective:To investigate the effects of zinc oxide nanoparticles (ZnO-NPs) on neutrophil hypoxia and pyroptosis through nucleotide binding of oligomeric domain-like receptor protein 3 (NLRP3) inflammasome, and to analyze the role of pyroptosis on respiratory tract inflammotion induced by ZnO-NPs.Methods:In October 2022, primary cultured neutrophils were obtained from the abdominal aortic blood of SPF adult healthy SD rats. The neutrophils were treated with ZnO-NPs solution (0, 5, 10, 20 μg/ml) at different concentrations, and hypoxia group (5% O 2) was set up. Hypoxia and reactive oxygen species (ROS) levels were detected by flow cytometry, and the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved Caspase-1 were measured by Western blot. The activity of lactic dehydrogenase (LDH) in the cell supernatant was measured by coloration, and the content of interleukin-1 beta (IL-1β) in cell culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA) . Results:Compared with the control group, hypoxia and ROS levels of neutrophils in hypoxia group and ZnO-NPs groups were significantly increased ( P<0.05), and NLRP3, ASC, cleaved Caspase-1 protein expression levels, LDH activity and IL-1β content were significantly increased ( P<0.05). Compared with hypoxia group, hypoxia and ROS levels of neutrophils in 5 μg/ml and 10 μg/ml ZnO-NPs groups were significantly decreased ( P<0.05), NLRP3, ASC, cleaved Caspase-1 protein expression levels, LDH activity, and IL-1β content were decreased significantly ( P<0.05). There were no significant differences in hypoxia, ROS levels, ASC, cleaved Caspase-1 protein expression levels, LDH activity, and IL-1β content between the 20 μg/ml ZnO-NPs group and the hypoxia group ( P>0.05) . Conclusion:ZnO-NPs treatment may activate the NLRP3 inflammasome to induce pyroptosis of neutrophils which may be related to ROS and hypoxia.

Objective: To analyze the association of strength quality of junior high school students with comorbid depressive and anxiety (CDA) and its subtypes, so as to provide reference for mental health improvement among junior high students. Methods: A convenient sampling method was used to select 10 007 junior high students aged 13-16 from four cities (Nanchang, Ganzhou, Jiujiang, Shangrao) in Jiangxi Province during September to November 2023. A questionnaire survey and physical fitness tests were employed to collect basic information and assess students depressive and anxiety status, as well as strength quality. The χ 2 test was used to compare the distribution differences of CDA and its subtypes among different demographic characteristics, sleep, physical activity, and overweight/obesity conditions. Logistic regression models were applied to infer the association strength between strength quality and CDA and its subtypes. Results: The overall detection rate of CDA among junior high students was 11.04%. Among the CDA subtypes, the detection rates for mild depression-mild anxiety type, anxiety dominant type, depressiondominant type, and severe depression-severe anxiety type were 3.67%, 3.35%, 0.39% and 3.64%, respectively. Compared to the grip strength and standing long jump scores in the > P 75 group, the risk of CDA occurrence increased in other groups (grip strength: P 25 - P 75 , OR =1.20; < P 25 , OR =1.28; standing long jump: P 25 - P 75 , OR =1.31; < P 25 , OR =1.51; P <0.05). In stratified analysis of different CDA subtypes, compared to the grip strength > P 75 group, the risks for mild depression-mild anxiety type increased in the P 25 - P 75 and < P 25 groups ( OR=1.32, 1.44, P <0.05). Compared to the standing long jump > P 75 group, the risks for anxiety dominant type and severe depression-severe anxiety type increased in other groups (anxiety dominant type: P 25 - P 75 , OR =1.32; severe depression-severe anxiety type: < P 25 , OR =1.87; P < 0.05 ). Conclusions Lower levels of grip strength and standing long jump performance among junior high students are positively correlated with CDA and its subtypes. Lower levels of lower limb strength may be an important predictor of CDA in severe depression and anxiety.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the effects of zinc oxide nanoparticles (ZnO-NPs) on neutrophil hypoxia and pyroptosis through nucleotide binding of oligomeric domain-like receptor protein 3 (NLRP3) inflammasome, and to analyze the role of pyroptosis on respiratory tract inflammotion induced by ZnO-NPs.Methods:In October 2022, primary cultured neutrophils were obtained from the abdominal aortic blood of SPF adult healthy SD rats. The neutrophils were treated with ZnO-NPs solution (0, 5, 10, 20 μg/ml) at different concentrations, and hypoxia group (5% O 2) was set up. Hypoxia and reactive oxygen species (ROS) levels were detected by flow cytometry, and the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved Caspase-1 were measured by Western blot. The activity of lactic dehydrogenase (LDH) in the cell supernatant was measured by coloration, and the content of interleukin-1 beta (IL-1β) in cell culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA) . Results:Compared with the control group, hypoxia and ROS levels of neutrophils in hypoxia group and ZnO-NPs groups were significantly increased ( P<0.05), and NLRP3, ASC, cleaved Caspase-1 protein expression levels, LDH activity and IL-1β content were significantly increased ( P<0.05). Compared with hypoxia group, hypoxia and ROS levels of neutrophils in 5 μg/ml and 10 μg/ml ZnO-NPs groups were significantly decreased ( P<0.05), NLRP3, ASC, cleaved Caspase-1 protein expression levels, LDH activity, and IL-1β content were decreased significantly ( P<0.05). There were no significant differences in hypoxia, ROS levels, ASC, cleaved Caspase-1 protein expression levels, LDH activity, and IL-1β content between the 20 μg/ml ZnO-NPs group and the hypoxia group ( P>0.05) . Conclusion:ZnO-NPs treatment may activate the NLRP3 inflammasome to induce pyroptosis of neutrophils which may be related to ROS and hypoxia.

Humans ; Tricuspid Valve/surgery* ; Heart Valve Prosthesis Implantation ; Surgical Instruments ; Treatment Outcome ; Cardiac Catheterization ; Tricuspid Valve Insufficiency/surgery*

Objective: To analyze the contribution and interaction of polycyclic aromatic hydrocarbons (PAH)-DNA adducts and changes of telomere length (TL) on missed abortion. Methods: From March to December 2019, patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group. Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects. The abortion villi were collected and the content of PAH-DNA adducts and TL was detected. Logistic regression model was used to analyze the associated factors of missed abortion. R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion. Results: The age of the subjects was(29.92±5.69)years old. The M(Q₁,Q₃)of PAH-DNA adducts was 453.75(404.61, 504.72) pg/ml. The M(Q₁,Q₃)of TL was 1.21(0.77, 1.72). The content of PAH-DNA adducts in the case group was higher than that in the control group (Z=-2.10, P=0.036), while the TL was lower than that in the control group (Z=-4.05, P<0.001). Multivariate logistic regression showed that low, medium and high levels of PAH-DNA adducts (OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64), and long, medium and short levels of TL (OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26) were all risk factors for missed abortion. The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level, and no mediating role of TL was found. The stratified analysis showed that when the TL level was longer (>1.21), the low and high levels of PAH-DNA adducts were associated with missed abortion (all P<0.05); when the TL level was shorter (<1.21), the medium level of PAH-DNA adducts was associated with abortion (P=0.025). At lower levels of PAH-DNA adducts, no effect of TL on missed abortion was observed, while, at higher levels, TL was strongly associated with missed abortion (OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04). The interaction analysis found that the AP was 0.72 (95%CI: 0.46-0.99), and the SI was 5.21 (95%CI: 2.30-11.77). Conclusion: The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion, and there may be a positive additive interaction between the two factors on missed abortion.
Humans ; Female ; Pregnancy ; Young Adult ; Adult ; DNA Adducts ; Abortion, Missed/chemically induced* ; Polycyclic Aromatic Hydrocarbons ; Abortion, Spontaneous/chemically induced* ; Telomere/chemistry*

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.
Animals ; Zebrafish ; Rhus/chemistry* ; Triterpenes/analysis* ; Coronary Disease ; Thrombosis