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.

Precision treatment of cancer has entered the era of immunotherapy represented by immune checkpoint inhibitors(ICIs).Tumor tissue-based detection,such as programmed cell death-ligand 1 and tumor mutational burden are common biomarkers used in clinical screening for the benefit groups of ICIs.However,the wide application of tissue-based detection has been limited for insufficient tumor tissue samples and the need for invasive and complex operation.The recent rise of peripheral blood biomarkers pro-vides an alternative non-invasive solution to address these defects.This review summarizes the research progress of peripheral blood biomarkers related to immune checkpoint inhibitors,in order to provide references in clinic for screening groups benefiting from ICIs.

Objective:To analyze the distribution of ages at the interhospital transfer of outborn very preterm infants in China and to compare their perinatal characteristics and outcomes at discharge and neonatal intensive care unit (NICU) treatment.Methods:A total of 3 405 outborn very premature infants with a gestational age of 24-31 +6 weeks who were transferred to the NICUs of the Chinese Neonatal Network (CHNN) in 2019 were included in this retrospective study. According to the age at transfer, they were divided into three groups: early transfer (≤1 d), delayed transfer (>1-7 d) and late transfer (>7 d) groups. Analysis of variance, t-test, Chi-square test (Bonferroni correction), Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the general clinical condition, treatment, and outcomes at discharge among the three groups. Results:The median gestational age was 29.7 weeks (28.3-31.0 weeks) and the average birth weight was (1 321.0 ± 316.5) g for these 3 405 infants. There were 2 031 patients (59.6%) in the early transfer group, 406 (11.9%) in the delayed transfer group and 968 (28.4%) in the late transfer group. Infants who received continuous positive airway pressure ventilation and tracheal intubation in the delivery room accounted for 8.4% (237/2 806) and 32.9% (924/2 805), respectively. A total of 62.7% (1 569/2 504) of the mothers received antenatal glucocorticoid therapy and the ratio in the early transfer group was 68.7% (1 121/1 631), which was higher than that in the delayed transfer group [56.1% (152/271), χ2=16.78, P<0.017] and the late transfer group [49.2% (296/602), χ2=72.56, P<0.017]. The total mortality rate of very premature infants was 12.7% (431/3 405), and the mortality rates in the early, delayed and late transfer groups were 12.4% (252/2 031), 16.3% (66/406) and 11.7% (113/968), respectively ( χ2=5.72, P=0.057). The incidences of severe intraventricular hemorrhage, late-onset sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge were all higher in the delayed and late transfer groups than in the early transfer group, respectively. The incidences of retinopathy of prematurity, retinopathy of prematurity requiring treatment and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge in the late transfer group were significantly higher than that in the delayed transfer group (Bonferroni correction, all P<0.017). In the late transfer group, the median age of very premature infants at discharge was 66.0 d (51.0-86.0 d), and the corrected gestational age at discharge was 38.9 weeks (37.1-41.2 weeks), and both were greater than those in the early transfer [48.0 d (37.0-64.0 d), Z=260.83; 36.9 weeks (35.7-38.3 weeks), Z=294.32] and delayed transfer groups [52.0 d (41.0-64.0 d), Z=81.49; 37.4 weeks (36.1-38.7 weeks), Z=75.97] (all P<0.017). Conclusions:Many very premature infants need to be transferred to higher-level hospitals after birth. The later the very premature infants are transferred, the higher the incidence of complications will be. It is suggested that intrauterine or early postnatal transport may improve the prognosis of very premature infants.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

AIM:To explore the effect and mechanism of hydrogen sulfide(H2S)on autophagy and angiogene-sis in skin wound of diabetic rats.METHODS:Among 36 healthy 8-week-old male Sprague-Dawley rats,12 rats were se-lected as control group,and the remaining rats were intraperitoneally injected with streptozotocin(STZ)to induce diabetic model and were randomly divided into diabetes mellitus(DM)group and NaHS(H2S donor)intervention(DM+NaHS)group,with 12 rats in each group.A skin trauma model was established by excising the skin of the back of rats in each group.The rats in DM+NaHS group were intraperitoneally injected with NaHS(56 μmol/kg),and the rats in control and DM groups were daily received the same volume of normal saline for 21 consecutive days.The healing of skin wound was measured on days 0,7,14 and 21 after operation.On the 21st day after surgery,the content of H2S in skin tissues was de-tected by C-7Az fluorescent probe,and the morphological changes and angiogenesis of wound tissues were observed by HE staining.The expression of CD31 was detected by immunofluorescence staining,and endothelial autophagy was detected by double staining of CD31 and beclin-1.The protein levels of cystathionine γ-lyase(CSE),CD31,microtubule-associated protein 1 light chain 3(LC3),beclin-1,P62,Bcl-2,Bax,phosphatidylinositol 3-kinase(PI3K),protein kinase B(PKB/Akt)and mammalian target of rapamycin(mTOR)in wound tissues were determined by Western blot.Caspase-3 and propidium iodide(PI)staining was used to detect cell apoptosis,and apoptosis of vascular endothelial cells was deter-mined with CD31 and TUNEL double immunofluorescence staining.RESULTS:Compared with DM group,the wound healing rate,H2S content and CSE protein expression were significantly increased in DM+NaHS group(P＜0.01),but still lower than those in control group(P＜0.01).HE staining showed that the wound surface in DM group was thin and wide,with few capillary,while that in DM+NaHS group was thicker with lots of capillary and wound width was reduced.Com-pared with DM group,CD31 expression was markedly increased(P＜0.01),the fluorescence intensity of caspase-3 and PI was significantly decreased(P＜0.01),and CD31+/beclin-1+ as well as CD31+/TUNEL+ cells were decreased(P＜0.01)in DM+NaHS group.Western blot analysis showed that compared with DM group,the levels of beclin-1,Bax and LC3-Ⅱ/LC3-Ⅰ were significantly decreased(P＜0.01),while the levels of P62 and Bcl-2,as well as ratios of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR were significantly increased(P＜0.01)in DM+NaHS group.CONCLUSION:H2S can promote skin wound healing,which may be related to activation of PI3K/Akt/mTOR signaling pathway,inhibition of endothelial au-tophagy and apoptosis,and promotion of angiogenesis in diabetic rats.

Objective:To investigate the clinical and molecular features of patients with CD7 +relapsed or refractory acute myeloid leukemia(r/rAML)and the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods:172 r/rAML patients who underwent allo-HSCT in department of hematology, Aerospace Center Hospital between January 1st 2017 and December 31st 2020 were retrospectively analyzed The patients were were divided into CD7 + group( n=75) and CD7 - group( n=97) according to the expression CD7 in the initial immunophenotype. Mann-Whitney U and Chi-square test were used to compare the clinical data, molecular and cytogenetic characteristics of the two groups of patients. Kaplan-Meier method was used to analyze the median progression-free survival (PFS) and median overall survival (OS) of the two groups of patients, and Cox regression screenthe prognostic factors of the patients. Results:The median follow-up time was 19 months. The recurrence rates were 23.71% and 50.67%, respectively in CD7 - and CD7 + group (χ 2=13.428 P<0.001). In relapsed patients, 86.96 percentage of CD7 - group did not express CD7 while 86.84 percentage of CD7 + group expressed CD7. The median PFS was 25 and 5 months in CD7 - and CD7 + group (χ 2=8.695, P=0.003), and the medianOS was 34 and 15 months in CD7 - and CD7 + group (χ 2=2.579, P=0.108). Univariate analysis showed that the CD7 +group, had the lower rates of morphological remission (χ 2=10.014, P=0.002), molecular remission (χ 2=22.809, P<0.001), and more male patients (χ 2=5.281, P=0.022). The incidence of CEBPA double-site mutation was higher (23.4% vs 8.2%, χ 2=8.180, P=0.004) and the rearrangement of RUNX1::RUNX1T1 was lower(4.0% vs18.6%, χ 2=8.362, P=0.004)in CD7 +group than in CD7 -group. Multivariate analysis showed that pre-transplant tumor load was the only prognostic factor for PFS (HR, 1.600; 95% CI, 1.203 to 2.127; P=0.001) and OS (HR, 1.737; 95% CI, 1.273 to 2.369; P<0.001) in r/r AML patients. Conclusion:CD7 expression is a risk factor for poor prognosis in r/r AML patients, and CD7 expression is stable after relapse. Positive CD7 can be used as a target for immune targeted therapy.

The changes in intestinal flora are usually associated with different gastrointestinal diseases, and intestinal flora homeostasis can enhance immune tolerance and regulate intestinal immune balance.Previous studies have found that the increase of the relative abundance of Bacteroides fragilis (B.fragilis) in Bacteroides intestinalis can significantly enhance the expression of intestinal regulatory T cells (Treg) and anti-inflammatory cytokines, thus alleviating intestinal inflammation.However, the mechanism of B.fragilis regulating intestinal immunity is still unclear.In this study, an acute colitis model was constructed by giving 3% DSS in drinking water solution to SPF-grade C57BL/6 mice for 7 days, and exogenous supplementation B.fragilis was given to mice by gastric gavage to study its regulatory effect on intestinal immunity and its mechanism of action.The results showed that B.fragilis could improve the intestinal flora disorder in mice with colitis and increase the content of short-chain fatty acids (SCFAs), the main metabolite of the intestinal flora.By extracting mouse tissue lymphocytes, naive CD4+ T cells, and liposome-modified siRNA knockdown mouse Smad3, it was further discovered by flow cytometry that B.fragilis induced the expression of intestinal Treg cells and related cytokines through the TGF-β/Smad3 signaling pathway, which enhanced intestinal regulatory immunity and alleviated colitis.It was also found that B.fragilis activated TGF-β by increasing the expression of reactive oxygen species (ROS), thus inducing Treg cell differentiation and playing an immunomodulatory role.

BACKGROUND: Antenatal corticosteroids (ACS) can significantly improve the outcomes of preterm infants. This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units (NICU) and to explore perinatal factors associated with ACS use, using the largest contemporary cohort of very preterm infants in China. METHODS: This cross-sectional study enrolled all infants born at 24 +0 to 31 +6 weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st, 2019 to December 30th, 2019. The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery. Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage. RESULTS: A total of 7828 infants were enrolled, among which 6103 (78.0%) infants received ACS. ACS use rates increased with increasing gestational age (GA), from 177/259 (68.3%) at 24 to 25 weeks' gestation to 3120/3960 (78.8%) at 30 to 31 weeks' gestation. Among infants exposed to ACS, 2999 of 6103 (49.1%) infants received a single complete course, and 33.4% (2039/6103) infants received a partial course. ACS use rates varied from 30.2% to 100% among different hospitals. Multivariate regression showed that increasing GA, born in hospital (inborn), increasing maternal age, maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS. CONCLUSIONS The use rate of ACS remained low for infants at 24 to 31 weeks' gestation admitted to Chinese NICUs, with fewer infants receiving a complete course. The use rates varied significantly among different hospitals. Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.
Humans ; Infant, Newborn ; Infant ; Pregnancy ; Female ; Gestational Age ; Infant, Premature ; Intensive Care Units, Neonatal ; Cross-Sectional Studies ; Adrenal Cortex Hormones/therapeutic use*

Objective:The aim of this study was to investigate the carrier ratio and the genotype of thalassemia among Tujia and Miao people of reproductive age in Chongqing.Methods:According to forward-looking design and multi-stage stratified cluster sampling method, fasting venous blood samples of Tujia and Miao people of reproductive age were collected from 11 survey sites in Chongqing from March to July 2019. Gap-PCR and high-throughput sequencing were used to screen thalassemia genes.Results:A total of 516 Tujia people (258 males, 258 females) and 270 Miao people (139 males, 131 females) were included in this study, and their age were (28.63 ± 5.26) and (28.62 ± 5.35) years, respectively. About 5.04% (26/516) Tujia people carried thalassemia gene, with 1.94% (10/516) and 2.52% (13/516) for α and β thalassemia, respectively. Three kinds of new variants (1 case of each variant), HBA 2: c.46G>A (Gly>Ser), HBB: c.*+129T>A and HBB: c.-39T>G with unclear pathogenicity, were identified in Tujia people. About 7.78% (21/270) Miao people carried thalassemia gene, among these, α and β thalassemia were 3.33% (9/270) and 4.44%(12/270), respectively. The most common mutation type of α-globin gene was -α 3.7/in the two ethnic groups. Three kinds of β-globin gene mutation types, Codons 41/42 (-TTCT) beta 0, Codon 17 (A>T) beta 0 and IVS-Ⅱ-654 (C>T) beta +, were the most common in Tujia people. Meanwhile, the chief β-globin gene mutation type was Codons 41/42 (-TTCT) beta 0 in Miao people. Conclusions:The carrying rate of thalassemia gene is higher in Tujia and Miao people in Chongqing, and the genotypes of thalassemia gene are different between Tujia and Miao people. The clinical significance of three kinds of new variants with unclear pathogenicity should be focused on.

Objective To analyze the situation of high-risk human papillomavirus(HPV) infection and its relationship with cervical lesions among rural women in Chongqing City. Methods A total of 20000 rural women were selected from the districts of Wanzhou, Yongchuan,Banan and Tongnan of Chongqing City from January to April 2016. The cervical cancer preliminary screening was performed by detecting HPV gynotyping. The cases of HPV 16 and HPV 18 positive or other 12 high risk HPV types positive with abnormal colposcopy examination conducted the colposcopy fixed point biopsy. Results The positive rate of high-risk HPV infection was 9.66% among rural women in Chongqing City. The positive rates of high-risk HPV infection and different types of high-risk HPV infection had difference among different age groups. Among women of high-risk HPV infection positive, the occurrence rate of CIN1 was 2.33 %,which of CIN2,CIN3 and AIS was 1.35 %,and which of cervical cancer was 0.31%, the incidence rate of different grades of cervical lesions had no statistical difference among different age groups. Among women with different types of high-risk HPV infection,the incidence rate of different grades of cervical lesions in women of HPV 16 positive was highest, those with the other 12 types of high risk HPV positive had the lowest occurrence rate of different grades of cervical lesions, the differences were statistically significant. Conclusion HPV genotyping detection can increase the efficiency of cervical cancer screen ing and is more suitable for the screening of large population.