Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100A8/9 expression.

The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis (UC), and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC development. Here, we find that the IL-17 receptor subunit, CMTM4, is reduced in UC patients and dextran sulfate sodium (DSS)-induced colitis. The deletion of CMTM4 (Cmtm4-/-) in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type, and the gut microbiome significantly changes in composition. The causal role of the gut microbiome is confirmed with a cohousing experiment. We further identify that S100a8/9 is significantly up-regulated in Cmtm4-/- colitis, with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency. CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway, further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis. Taken together, the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis, suppression of S100a8/9, and prevention of colitis development. Our study further shows CMTM4 as a crucial innate immunity component, confirming its important role in the UC development and providing insights into potential targets for the development of future therapies.

Aggregation-Enabled Electrochemistry in Confined Nanopore Capable of Complementary Faradaic and Non-Faradaic Detection.

Electrochemistry that empowers innovative nanoscopic analysis has long been pursued. Here, the concept of aggregation-enabled electrochemistry (AEE) in a confined nanopore is proposed and devised by reactive oxygen species (ROS)-responsive aggregation of CdS quantum dots (QDs) within a functional nanopipette. Complementary Faradaic and non-Faradaic operations of the CdS QDs aggregate could be conducted to simultaneously induce the signal-on of the photocurrents and the signal-off of the ionic signals. Such a rationale permits the cross-checking of the mutually corroborated signals and thus delivers more reliable results for single-cell ROS analysis. Combined with the rich biomatter-light interplay, the concept of AEE can be extended to other stimuli-responsive aggregations for electrochemical innovations.

Comparison of 18 F-FDG and 18 F-FAPI PET/CT Findings of Signet-Ring Cell Carcinoma of the Stomach.

ABSTRACT: A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18 F-FDG and 18 FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18 FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.

Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network / 中华儿科杂志

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Antitumor effect of luteolin proven by patient-derived organoids of gastric cancer.

Luteolin (Lut) has been shown to inhibit gastric cancer (GC); however, its efficacy compared to other clinical drugs has not been examined in human samples. This study aimed to elucidate the antitumor activity of Lut in GC patient-derived organoids (PDOs). PDOs were established from GC cancer tissues, and the characterization of tissues and PDOs was performed using whole-exome sequencing. Drug sensitivity tests were performed by treating PDOs with Lut, norcantharidin (NCTD), and carboplatin (CP). RNA sequencing of PDOs was performed to elucidate the antitumor mechanism of Lut, which was further verified in three GC cell lines. Eleven PDOs were successfully constructed, and were highly consistent with the pathophysiology and genetic changes in the corresponding tumors. The IC50s of Lut, NCTD, and CP of PDOs were 27.19, 23.9, and 37.87 µM, respectively. Lut treatment upregulated FOXO3, DUSP1, and CDKN1A expression and downregulated IL1R1 and FGFR4 expression in GC cell lines, which was consistent with the results of PDOs. We demonstrate that Lut exerted stronger antitumor effects than CP, but a similar effect to that of NCTD, which was obtained in an in vitro PDO system. Additionally, Lut exerted varying degrees of antitumor effects against the PDOs, thereby indicating that PDO may be a useful preclinical drug screening tool for personalized treatment.

Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing.

BACKGROUND: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. METHODS: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. RESULTS: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. CONCLUSIONS: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment.

The relationship between probiotics and retinopathy of prematurity in preterm infants: A population-based retrospective study in China.

Background: Retinopathy of prematurity (ROP) is a retinal vascular disease with a high incidence in premature infants and is a leading cause of childhood blindness worldwide. The purpose of our study was to analyze the association between the use of probiotics and retinopathy of prematurity. Methods: This study retrospectively collected clinical data of premature infants with gestational age <32 weeks and birth weight <1500 g admitted to the neonatal intensive care unit from January 1, 2019 to December 31, 2021 in Suzhou Municipal Hospital, China. Demographic and clinical data of the inclusion population were collected. The outcome was the occurrence of ROP. The chi-square test was used to compare categorical variables, while the t-test and the nonparametric Mann-Whitney U rank-sum test were used for continuous variables. Univariate and multivariate logistic regression were used to analyze the relationship between probiotics and ROP. Results: A total of 443 preterm infants met the inclusion criteria, of which 264 didn't receive probiotics and 179 were supplemented with probiotics. There were 121 newborns with ROP in the included population. The results of univariate analysis showed that the preterm infants with and without probiotics were significantly different in the gestational age, the birth weight, the one-minute Apgar score, the oxygen inhalation time, the acceptance rate of invasive mechanical ventilation, the prevalence of bronchopulmonary dysplasia, ROP and severe intraventricular hemorrhage and periventricular leukomalacia (P < 0.05). Unadjusted univariate logistic regression model result showed that probiotics (OR 0.383, 95% CI 0.240∼0.611) were the factors affecting ROP in preterm infants (P < 0.01). Multivariate logistic regression result (OR 0.575, 95% CI 0.333∼0.994) was consistent with univariate analysis (P < 0.05). Conclusion: This study showed that probiotic was associated with a reduced risk of ROP in preterm infants with gestational age of <32 weeks and birth weight of <1500 g, but more large-scale prospective studies are still needed.

Medial meniscus posterior root tears and partial meniscectomy significantly increase stress in the knee joint during dynamic gait.

PURPOSE: As a simple and invasive treatment, arthroscopic medial meniscal posterior horn resections (MMPHRs) can relieve the obstructive symptoms of medial meniscus posterior root tears (MMPRTs) but with the risk of aggravating biomechanical changes of the joint. The aim of this study was to analyze dynamic simulation of the knee joint after medial meniscus posterior root tear and posterior horn resection. METHODS: This study established static and dynamic models of MMPRTs and MMPHRs on the basis of the intact medial meniscus model (IMM). In the finite element analysis, the three models were subjected to 1000 N axial static load and the human walking gait load defined by the ISO14243-1 standard to evaluate the influence of MMPRTs and MMPHRs on knee joint mechanics during static standing and dynamic walking. RESULTS: In the static state, the load ratio of the medial and lateral compartments remained nearly constant (2:1), while in the dynamic state, the load ratio varied with the gait cycle. After MMPHRs, at 30% of the gait cycle, compared with the MMPRTs condition, the maximum von Mises stress of the lateral meniscus (LM) and the lateral tibial cartilage (LTC) were increased by 166.0% and 50.0%, respectively, while they changed by less than 5% during static analysis. The maximum von Mises stress of the medial meniscus (MM) decreased by 55.7%, and that of the medial femoral cartilage (MFC) increased by 53.5%. CONCLUSION: After MMPHRs, compared with MMPRTs, there was no significant stress increase in articular cartilage in static analysis, but there was a stress increase and concentration in both medial and lateral compartments in dynamic analysis, which may aggravate joint degeneration. Therefore, in clinical treatments, restoring the natural structure of MMPRTs is first recommended, especially for physically active patients.

Chr9∶52042693|52047844⁃miR⁃351⁃5p⁃Pten Is Involved in the Development and Progression of Obstructive Sleep Apnea Syndrome through a ceRNA Mechanism / 中国生物化学与分子生物学报

Intermittent hypoxia (IH) is an important pathophysiological feature of obstructive sleep apnea (OSA), but its molecular mechanism is still unclear. We aim to investigate the role of endogenous competing endogenous RNA (ceRNA) regulatory network in the development of IH in OSA rats. An intermittent hypoxic rat model of OSA was constructed by hypoxic and reoxygenation cycles. CircRNAs and mRNAs were detected in rat bronchial tissues, and 230 up-regulated and 181 down-regulated circRNAs and 1238 up-regulated and 608 down-regulated mRNAs were analyzed and screened. The results of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential circRNAs and mRNAs suggested that they were mainly associated with metabolic pathways and PI3K-Akt signaling pathways. The key circRNAs (the top six circRNAs with the largest differences) were further validated by quantitative real-time polymerase chain reaction (qRT-PCR), chr9:52042693| 52047844 and chr4: 64889575|64899587 were expressed in bronchial tissues consistent with the sequencing results, which were used to further construct the ceRNA regulatory network. Four potential ceRNA regulatory networks were identified by TargetScan and miRanda database, combined with the results of differential circRNA and mRNA. The expression of molecules in the four potential ceRNA regulatory networks was detected by qRT-PCR in bronchial and lung tissues, and the results suggested that the expression of this regulatory network, chr9:52042693|52047844-miR-351-5p-Pten, was consistent with the sequencing results. The findings indicate that chr9:52042693 | 52047844-miR-351-5p-Pten may be involved in the development and progression of obstructive sleep apnea syndrome through a ceRNA mechanism.

Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China / 中华儿科杂志

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

[Paths of soil erosion controlled by typical soil and water conservation practices based on the SIMWE model: A case study of the Tongshuang watershed.] / 基于SIMWEæ¨¡åž‹çš„å ¸åž‹æ°´åœŸä¿æŒæŽªæ–½ä¾µèš€é˜»æŽ§è·¯å¾„åˆ†æž­­ä»¥é€šåŒå°æµåŸŸä¸ºä¾‹.

Due to the basic topographical characteristics of the gentle and long slope lengths in the Mollisol region of Northeast China, severe soil erosion is easily aggravated by the concentration of surface flow. The spatial distribution of water depth and hydrological connectivity index were introduced to evaluate the effects of typical soil and water conservation practices on the overland flow path and hydrological connectivity based on the GIS and SIMWE (SIMulated Water Erosion) model. We analyzed the effects of different soil and water conservation practices on the hydrological connectivity, water flow path, and spatial distribution of soil erosion and sediment yield by quantifying the variations of soil infiltration rate and surface manning roughness, as well as by constructing an artificial terrain digital elevation model (DEM). The results showed that: 1) terraces could effectively affect the hydrological connectivity of the slope and regulate flow path, with significant differences between the responses of hydrological connectivity and flow path under different forms of terraced fields and ridges. The characteristics of spatial distribution of soil erosion and sediment yield varied with changes in water flow path, which would eventually lead to the intensification of local erosion; 2) practices of vegetated buffer strips and contour tillage presented limited effectiveness on runoff path controlling, though they played a significant role in sediment retention; and 3) conservation tillage could reduce the hydrological connectivity and improve the retention capacity of runoff by increasing surface roughness. This study quantified the effects of different soil and water conservation practices on the hydrological connectivity, flow path, and spatial distribution of soil erosion and sediment yield, and could provide a theoretical reference for scientific layout of soil and water conservation practices in black soil region.

Human iPSC-derived hepatocyte system models cholestasis with tight junction protein 2 deficiency.

Background & Aims: The truncating mutations in tight junction protein 2 (TJP2) cause progressive cholestasis, liver failure, and hepatocyte carcinogenesis. Due to the lack of effective model systems, there are no targeted medications for the liver pathology with TJP2 deficiency. We leveraged the technologies of patient-specific induced pluripotent stem cells (iPSC) and CRISPR genome-editing, and we aim to establish a disease model which recapitulates phenotypes of patients with TJP2 deficiency. Methods: We differentiated iPSC to hepatocyte-like cells (iHep) on the Transwell membrane in a polarized monolayer. Immunofluorescent staining of polarity markers was detected by a confocal microscope. The epithelial barrier function and bile acid transport of bile canaliculi were quantified between the two chambers of Transwell. The morphology of bile canaliculi was measured in iHep cultured in the Matrigel sandwich system using a fluorescent probe and live-confocal imaging. Results: The iHep differentiated from iPSC with TJP2 mutations exhibited intracellular inclusions of disrupted apical membrane structures, distorted canalicular networks, altered distribution of apical and basolateral markers/transporters. The directional bile acid transport of bile canaliculi was compromised in the mutant hepatocytes, resembling the disease phenotypes observed in the liver of patients. Conclusions: Our iPSC-derived in vitro hepatocyte system revealed canalicular membrane disruption in TJP2 deficient hepatocytes and demonstrated the ability to model cholestatic disease with TJP2 deficiency to serve as a platform for further pathophysiologic study and drug discovery. Lay summary: We investigated a genetic liver disease, progressive familial intrahepatic cholestasis (PFIC), which causes severe liver disease in newborns and infants due to a lack of gene called TJP2. By using cutting-edge stem cell technology and genome editing methods, we established a novel disease modeling system in cell culture experiments. Our experiments demonstrated that the lack of TJP2 induced abnormal cell polarity and disrupted bile acid transport. These findings will lead to the subsequent investigation to further understand disease mechanisms and develop an effective treatment.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Vancomycin in neonatal sepsis: predictive performance of a Chinese neonatal population pharmacokinetic model and clinical efficacy evaluation.

BACKGROUND: In the neonatal population, individual calculation and adjustment of vancomycin (VCM) doses has been recommended based on population pharmacokinetics (PPK) methods. OBJECTIVE: Our previous study established a Chinese neonatal VCM PPK model. The main goal of this study was to evaluate the predictive performance of this PPK model for VCM trough concentration. METHODS: The data on neonatal severe infection patients treated with VCM were retrospectively collected. The predictive performance of this PPK model was expressed using mean prediction error (MPE), mean absolute prediction error (MAPE), sensitivity and specificity. Linear regression analysis was used to compare predicted and measured VCM concentrations. We drew the receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of the ratio of area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC0-24/MIC) and trough concentration for clinical efficacy. RESULTS: A total of 40 neonates with Gram-positive bacterial sepsis were included. After VCM treatment, 32 (80%) neonates were clinically cured. Eight cases were a clinical failure: the trough concentrations and AUC0-24 were lower than that of the clinical cure patients (8.70±4.30 vs 14.30±4.50 mg/L, p=0.003; 404.30±122.80 vs 515.40±131.70, p=0.037). The measured and predicted trough concentration were 11.16 (5.96, 16.53) mg/L and 10.13 (6.61, 15.73) mg/L, respectively. The MPE and MAPE were 4.62% and 13.26% (5.30%, 25.88%), respectively. The proportion of MAPE <30% in the adjusted regimen was higher than the initial regimen (89.66% vs 65.00%, p=0.039). Predictions of sensitivity and specificity by this PPK model were 88.24% and 94.29%, respectively. The coefficients of determination of linear regression analysis were 0.9171 and 0.9009 for the initial and adjusted regimen, respectively. The AUC0-24 was correlated with the trough concentration (r=0.587, p<0.001). The ROC curve indicated that the optimal cut-off points for predicting clinical efficacy were AUC0-24/MIC >425.47 and trough concentration >9.45 mg/L. CONCLUSION: This PPK model has good predictive performance in Chinese neonatal patients. Both AUC0-24/MIC and trough concentration can predict the clinical efficacy of antibacterial treatment.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study / 中国当代儿科杂志

OBJECTIVES@#To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.@*METHODS@#A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.@*RESULTS@#The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).@*CONCLUSIONS@#It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Chronic Active Hepatitis B with COVID-19 in Pregnancy: A Case Report.

Currently, infection with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during pregnancy is a problem worthy of attention, especially in patients with underlying diseases. In this case report, we present a case of chronic active hepatitis B with COVID-19 in pregnancy. A 31-year-old woman at 29 weeks of gestation who had a history of chronic hepatitis B virus infection discontinued antiviral treatment, was admitted to the hospital with chronic active hepatitis B, and tested positive for SARS-CoV-2 infection. In this case, we applied liver protective and antiviral agents, and low-dose dexamethasone therapy to successfully treat the critically ill pregnant woman suffering from chronic active hepatitis B combined with COVID-19.

Circulating miR-19a-3p and miR-483-5p as Novel Diagnostic Biomarkers for the Early Diagnosis of Gastric Cancer.

BACKGROUND MicroRNAs (miRNAs) are attracting substantial interest as promising noninvasive biomarkers for gastric cancer (GC). Our study aimed to identify circulating miRNAs that are potential noninvasive markers for precancerous lesions and early gastric cancers (EGCs). MATERIAL AND METHODS Plasma specimens were obtained from 58 gastritis subjects, 54 patients with precancerous lesions, and 38 EGC patients for study. RESULTS Significant differences in the plasma expression levels of miR-19a-3p, miR-22-3p, miR-146a-5p, and miR-483-5p (all P<0.05) were observed between EGC patients and gastritis subjects. Multivariable analysis showed that age (OR, 1.054; 95% CI, 1.006-1.104), miR-19a-3p expression (OR, 3.676; 95% CI, 1.914-7.061), and miR-483-5p expression (OR, 1.589; 95% CI, 1.242-2.033) were independently associated with EGCs and precancerous lesions. A combined diagnostic model incorporating these 3 variables for the prediction of EGCs and precancerous lesions was derived. The area under the receiver operating characteristic curve (AUC) of the model was 0.84; the sensitivity was 87.7% and the specificity was 62.8% at the cutoff value of -0.08. CONCLUSIONS Plasma miR-19a-3p and miR-483-5p are promising and powerful noninvasive markers for the early detection of GC. Patients are more willing to undergo noninvasive diagnostic procedures than gastroscopy for cancer screening, economizing limited medical resources.

[Safety and efficacy of caffeine use started at different time in preterm infants: a multicenter study in Jiangsu Province, China].

OBJECTIVE: To study the efficacy and safety of caffeine used in the early (≤72 hours after birth) and late (>72 hours after birth) stage in preterm infants with a gestational age of ≤31 weeks. METHODS: A retrospective analysis was performed for 640 preterm infants (with a gestational age of ≤31 weeks) who were admitted to the neonatal intensive care unit of eight hospitals in Jiangsu Province, China. Of the 640 preterm infants, 510 were given caffeine in the early stage (≤72 hours after birth; early use group) and 130 were given caffeine in the late stage (>72 hours after birth; late use group). The clinical data were compared between the two groups. RESULTS: There were no significant differences in birth weight, Apgar score, sex, gestational age, and age on admission between the two groups (P>0.05). Compared with the late use group, the early use group had a significantly younger age at the beginning and withdrawal of caffeine treatment (P<0.05) and a significantly shorter duration of caffeine treatment (P<0.05). There was no significant difference in respiratory support on admission between the two groups (P>0.05). Compared with the late use group, the early use group had significantly lower incidence rate of apnea (P<0.05) and significantly shorter oxygen supply time and length of hospital stay (P<0.05). There were no significant differences between the two groups in the incidence rates of neonatal intracranial hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, and patent ductus arteriosus at discharge and NBNA score at the corrected gestational age of 40 weeks (P>0.05). However, significant differences were found in the incidence of bronchopulmonary dysplasia and the rate of home oxygen therapy, but there was no significant difference in the mortality rate between the two groups (P>0.05). CONCLUSIONS: Early use of caffeine can shorten the duration of caffeine treatment, oxygen supply time, and length of hospital stay, with little adverse effect, in preterm infants with a gestational age of ≤31 weeks.

A novel viologen-based coordination polymer with multi-stimuli responsive chromic properties: photochromism, thermochromism, chemochromism and electrochromism.

Increasing interest in chromic materials is due to the growing demand. However, most chromic materials exhibit color changes in response to only one stimulus, but there are multiple stimuli in nature. Therefore, the construction of multistimuli responsive chromic materials still faces great challenges. Herein, a new multi-stimuli responsive coordination polymer [Zn2(2,3-PDC)2CV·(H2O)2]·H2O (1) (2,3-PDC = 2,3-pyridine dicarboxylic acid, CV = N,N'-4,4'-bipyridiniodipropionate) has been successfully synthesized, which exhibits photochromism under 300 W xenon lamp irradiation accompanied by an obvious color change from colorless to light blue. Meanwhile, compound 1 displays excellent thermochromic properties with a color change from colorless to light yellow when heated at 106 °C. The product of thermochromism is named 1T and the loss of free water improves the photoresponsive properties of 1T. Moreover, the compound can show differentiable detection of amines because of the electron-deficient nature of the viologen. Finally, 1 shows excellent electrochromic properties and turns from colorless to purple at E = -3 V. In conclusion, compound 1 exhibits multi-chromic behaviors in response to light, heat, amines and electricity, which are prominent in viologen based coordination polymers.