OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.
Carbohydrates ; Glycosides ; Oligosaccharides ; Oxidation-Reduction ; Polysaccharides/chemistry*

Aim To observe the inhibitory effect of neferine(Nef)on the migration and invasion of non-small cell lung cancer(NSCLC)H1299 cells by blocking ROCK pathway.Methods H1299 cells were taken for in vitro culture, and treated with different concentrations of Nef.H1299 cell viability was measured by CCK-8 method to determine the dose of the experimental group.The migration and invasion abilities of H1299 cells were detected by cell scratch test and Transwell chamber test.The expression of matrix metalloproteinases MMP-2 and MMP-9 secreted from lung cancer cells was detected by enzyme linked immunosorbent assay(ELISA).The protein level of ROCK1 in H1299 cells was tested by real-time fluorescent quantitative PCR and Western blot; the binding mode and affinity between Nef and ROCK1 were stimulated by AutoDock semi flexible docking method.Results The doses of Nef in the experimental group were determined as 4, 6 and 10 μmol·L-1.These three concentrations of Nef could inhibit the migration and invasion of H1299 lung cancer cells to a certain degree in a dose-dependent manner.At the same time, Nef reduced the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.In addition, the affinity of Nef to ROCK1 was significantly higher than that of fasudil, an inhibitor of ROCK, and the binding force was stronger to A-chain of ROCK1.Conclusions As a potential natural anticancer compound, Nef can inhibit the migration and invasion of NSCLC by reducing the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ²= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.
Child ; Electrolytes ; Female ; Humans ; Male ; Metoprolol ; Midodrine ; Orthostatic Intolerance/therapy* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Salts ; Sitting Position ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

Objective:To observe the effect of Jianpi Xiaoai prescription on long non-coding RNA Hox transcript antisense intergenic RNA （lncRNA HOTAIR）/Janus kinase 2 （JAK2） /signal transducer and activator of transcription 3 （STAT3） signaling pathway and to explore the potential mechanism of Jianpi Xiaoai prescription in suppressing the metastasis of colon cancer. Method:The expression of lncRNA HOTAIR in different cells was analyzed. Following the treatment of HCT116 cells with 10%，15%，and 20% Jianpi Xiaoai prescription -containing serum， the invasive ability of Jianpi Xiaoai prescription on HCT116 cells was assessed by transwell assay. The mRNA expression levels of lncRNA HOTAIR，JAK2，and STAT3 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of JAK2， phosphorylated STAT3 （p-STAT3） and STAT3 by Western blot. Result:The highest expression of lncRNA HOTAIR was detected in HCT116 cells. Compared with the blank group， each Jianpi Xiaoai prescription group exhibited a decreased number of invasive cells （P<0.05， P<0.01）. The relative JAK2 mRNA expression in the middle-dose Jianpi Xiaoai prescription group was down-regulated （P<0.05）， and the relative lncRNA HOTAIR mRNA expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative JAK2 mRNA expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated （P<0.01）. Compared with the blank group，the relative p-STAT3 protein expression was down-regulated in the middle-dose Jianpi Xiaoai prescription group （P<0.05）， and the relative JAK2 protein expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative p-STAT3 protein expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated （P<0.01）. Conclusion:Jianpi Xiaoai prescription effectively inhibits the metastasis of colon cancer cells， which may be related to the inhibition of lncRNA HOTAIR/JAK2/STAT3 signaling pathway.

Objective: To investigate the effect of centrosomal protein Cep63 on the apoptosis of papillary thyroid carcinoma (PTC) cell lines TPC-1 and underlying mechanism. Methods: With collected PTC tissues and adjacent tissues, Cep63 expression was detected by RT-qPCR and its relationship with clinicopathological factors was analyzed. The experiment included negative control group (NC), low expression group (Cep63(-)) and overexpression group (Cep63(+)), and wild-type TPC-1 cells were transfected with Cep63 lentivirus. The efficiency of Cep63 was detected by western blot (WB) and qRT-PCR. Cell proliferation ability was detected by plate cloning experiment and MTT assay. Cell apoptotic rate was detected by flow cytometry, and expression levels of apoptosis-related proteins were detected by immunohistochemistry and WB. The t-test was used to compare the differences in the means between the two groups, the one-way analysis of variance was used to compare multiple groups, and the chi-square test was used to analyze the association between gene expression levels and pathological factors. Results: Compared with NC group, cell proliferation ability was significantly decreased in Cep63(-) group (3.18±0.07 vs. 2.14±0.09, t=8.54, P<0.01) and significantly increased in Cep63(+) group (3.18±0.07 vs. 3.58±0.10, t=3.21, P<0.05). Apoptotic rates in NC, Cep63 (-) and Cep63 (+) groups were respectively 3.03%±0.24%, 8.66%±0.44% and 1.17%±0.44%, and the flow cytometry showed that the low expression of Cep63 significantly increased the apoptosis TPC-1 cells (F=157.7, P<0.001). Bcl-2 protein expression levels of NC, Cep63 (-) and Cep63 (+) groups were respectively 1.07±0.03, 0.49±0.01 and 1.99±0.09, and BAX protein expression levels of three groups were respectively 0.64±0.02, 1.06±0.01 and 0.21±0.03. WB showed that the expression level of Bcl-2 decreased (F=183.2, P<0.001), while the expression level of BAX was significantly up-regulated (F=283.7, P<0.001). Conclusion: Cep63 may regulate the apoptotic process of TPC-1 cells through Bcl-2/BAX pathway and Cep63 may be a potential oncogene of PTC.
Apoptosis ; Carcinoma, Papillary/genetics* ; Cell Cycle Proteins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

The human UDP-glucuronosyltransferase 1A1 (UGT1A1), one of the most essential conjugative enzymes, is responsible for the metabolism and detoxification of bilirubin and other endogenous substances, as well as many different xenobiotic compounds. Deciphering UGT1A1 relevance to human diseases and characterizing the effects of small molecules on the activities of UGT1A1 requires reliable tools for probing the function of this key enzyme in complex biological matrices. Herein, an easy-to-use assay for highly-selective and sensitive monitoring of UGT1A1 activities in various biological matrices, using liquid chromatography with fluorescence detection (LC-FD), has been developed and validated. The newly developed LC-FD based assay has been confirmed in terms of sensitivity, specificity, precision, quanti-tative linear range and stability. One of its main advantages is lowering the limits of detection and quantification by about 100-fold in comparison to the previous assay that used the same probe substrate, enabling reliable quantification of lower amounts of active enzyme than any other method. The precision test demonstrated that both intra- and inter-day variations for this assay were less than 5.5％. Further-more, the newly developed assay has also been successfully used to screen and characterize the regu-latory effects of small molecules on the expression level of UGT1A1 in living cells. Overall, an easy-to-use LC-FD based assay has been developed for ultra-sensitive UGT1A1 activities measurements in various biological systems, providing an inexpensive and practical approach for exploring the role of UGT1A1 in human diseases, interactions with xenobiotics, and characterization modulatory effects of small mole-cules on this conjugative enzyme.

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, CONCLUSIONS Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
Beijing/epidemiology* ; Breast Feeding ; China/epidemiology* ; Communicable Diseases/epidemiology* ; Female ; Hospitalization ; Hospitals ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Pregnancy

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult