Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

Objective:To compare the short-term outcomes of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants supplementarily fed with fortified donor human milk (DHM) or preterm formula (PF) when the mother's own milk (MOM) is insufficient.Methods:This retrospective cohort study included 91 VLBW or ELBW preterm infants with birth weight<1 500 g who were hospitalized in Peking Union Medical College Hospital from October 1, 2017, to September 30, 2020. Based on the supplemental feeding method when MOM was insufficient, these infants were divided into the DHM group ( n=51) and PF group ( n=40). Mann-Whitney U, t-test, Chi-square test, or Fisher's exact test were used to compare the short-term clinical outcomes during hospitalization between the two groups. Results:(1) There were no statistically significant differences between the 91 preterm infants in the DHM group and PF group in their gestational age, birth weight, sex ratio, birth mode, mothers' age at delivery, or the proportion of infants of small gestational age (all P>0.05). (2) The feeding volume in the DHM group was significantly greater than that in the PF group on the 14th day after birth [(108.2±53.1) vs. (81.0±47.8) ml/(kg·d), t=0.78, P=0.020]. Moreover, the time to achieve the feeding amounts up to 120 ml/(kg·d) and 150 ml/(kg·d) for infants in the DHM group were significantly shorter than those in the PF group [(17.5±10.2) vs. (30.0±12.0) d, t=4.38; (22.1±13.3) vs. (32.3±11.9) d, t=0.02; both P<0.05]; (3) Lower proportion of peripherally inserted central catheter (PICC) [58.8% (30/51) vs. 100% (40/40), χ 2=21.88, P<0.001] and shorter PICC duration were observed in the DHM group [10.0 (0.0-19.0) vs. 29.0 (17.0-40.5) d, Z=5.56, P<0.001] compared to the PF group. The times of red blood cell transfusions and the incidence of late sepsis in the DHM group were less than those in the PF group [0.0 (0.0-2.0) vs. 2.0 (1.0-3.0) times, Z=4.44, P<0.001; 23.5% (12/51) vs. 50.0% (20/40), χ 2=6.39, P=0.011]. There were no statistically significant differences observed in the incidence of bronchopulmonary dysplasia, neonatal necrotizing enterocolitis, retinopathy of prematurity, and the length of hospitalization (all P>0.05). Conclusion:When MOM is insufficient, supplementing VLBW and ELBW infants with fortified donor human milk can shorten the time to achieve enteral nutrition and reduce the use rate and time of PICC, the incidence of late-onset sepsis, and the times of red blood cell transfusion.

Objective:To explore chromosomal copy number variations (CNVs) and pregnancy outcomes in fetuses with mild to moderate isolated ventriculomegaly (IVM), but without other indications for invasive prenatal diagnosis.Methods:A retrospective analysis was conducted on clinical data of 215 singleton pregnancies with mild to moderate IVM (lateral ventricular width≥10-<15 mm) who underwent chromosomal microarray analysis (CMA), not indicated by advanced age, high risk in serum screening or abnormal history of pregnancy, at the Fujian Maternity and Child Health Hospital between June 2016 and March 2023. The 215 fetuses were grouped into mild ( n=167) and moderate ( n=48) IVM;unilateral ( n=142) and bilateral ( n=73) IVM; first diagnosis of IVM before 28 weeks ( n=138) and thereafter ( n=77). Anomalies other than IVM were excluded via three-dimensional color Doppler ultrasound examination between 22 and 26 weeks of gestation. Out of these cases, 129 were confirmed by fetal cranial MRI, 191 underwent chromosomal karyotype analysis, and 202 cases received cytomegalovirus DNA quantification test for amniotic fluid. The detection rates of pathogenic CNVs in various groups were compared using Fisher's exact test. Results:Among the 215 fetuses, 11 cases (5.1%) of chromosomal abnormalities were detected through CMA, including one trisomy 21, five pathogenic CNVs, and five CNVs of uncertain clinical significance. Within the pathogenic CNVs, there were two de novo mutations with 16p11.2 microdeletion and one de novo mutation with 16p11.2 microduplication, while one 16p11.2 microduplication and one Xp22.31 microdeletion were inherited maternally. Of the CNVs of uncertain significance, there were two 16p13.11 microduplications, each inherited from a different parent, one paternally and one maternally; meanwhile, family validation was refused in the other three cases with 3p22.1 microdeletion, 3p26.3 microdeletion, and 9q21.33q22.31 microduplication. The detection rate of pathogenic CNVs in the moderate IVM group was higher than that in the mild IVM group [6.3% (3/48) vs. 1.2% (2/167)], but the difference was not statistically significant ( P=0.083). Similarly, no significant difference was found in the detection rate of pathogenic CNVs when comparing the unilateral IVM group [2.1% (3/142)] with the bilateral IVM group [2.7% (2/73)], nor between the group diagnosed with VM before 28 weeks gestation [2.2% (3/138)] and that diagnosed ≥28 weeks [2.6% (2/77)] (both P>0.05). After the exclusion of fetuses with chromosomal pathogenic abnormalities ( n=11), cytomegalovirus infection( n=1), and additional ultrasound anomalies ( n=7), and several cases with missing data intrauterine outcomes were followed up in 169 IVM fetuses, including 104 (61.5%) improved, 60 (35.5%) unchanged, and five (3.0%) progressed. Follow-ups were successful for 194 women, of which eight pregnancies were terminated (including one trisomy 21, four pathogenic CNVs, one fetal cytomegalovirus infection, and two progressed to severe IVM). Among the 186 newborns, one was diagnosed with X-linked ichthyosis, and one child who progressed to severe IVM before born was followed until 20 months of age without notable phenotypic abnormalities. The rest 184 babies, including those with CNVs of uncertain clinical significance, exhibited no developmental abnormalities during follow-up between the ages of three months and six years. Conclusions:For those fetuses with isolated mild to moderate IVM, but without indications for prenatal diagnosis such as advanced maternal age, high risk in serum screening or abnormal history of pregnancy, remain having the risk for chromosomal aberrations, and 16p11.2 microdeletion/microduplication might be a frequent CNV associated with this condition. Aside from those with pathogenic chromosomal aberrations, fetal cytomegalovirus infection, or progressive enlargement of the lateral ventricles, most fetuses with isolated mild to moderate IVM have a good prognosis.

Objective To observe the difference and clinical significance of expression levels of microRNA-155(miR-155)mRNA and interleukin-6(IL-6)in very preterm neonates with preeclampsia.Methods Twenty-eight cases of very preterm newborns(gestational age<32 weeks and/or body weight<1500 g)from preeclampsia pregnant women admitted to the department of obstetrics of Liaocheng People's Hospital from January to December 2021 were selected as the observation group,and 26 cases of very preterm neonates hospitalized for other reasons during the same period were selected as the control group.Electronic medical record clinical data related to children were collected,and the differences between the two groups were compared,including general conditions of preterm infants and pregnant mothers(gender,gestational age,birth weight,preeclampsia or not),proportion of invasive ventilation,proportion of bronchopulmonary dysplasia(BPD),incidence of acute respiratory distress syndrome(ARDS)and early-onset sepsis,white blood cell count(WBC),neutrophil count(NEUT),and expression of miR-155 mRNA and IL-6 levels in the serum of umbilical arterial blood after birth.Pearson correlation analysis was used to analyze the correlation between miR-155 and IL-6 levels Results The birth body weight of the observation group was significantly lower than that of the control group(kg:1.21±0.22 vs.1.32±0.33,P<0.05),the proportion of invasive ventilation,the proportion of BPD,the incidence of ARDS and sepsis were significantly higher than those in the control group[the proportion of invasive ventilation:75.0%(21/28)vs.57.7%(15/26),the proportion of BPD:35.7%(10/28)vs.11.5%(3/26),incidence of ARDS:100.0%(28/28)vs.84.6%(22/26),incidence of sepsis:71.4%(20/28)vs.53.8%(14/26),all P<0.05],the level of miR-155 mRNA expression and IL-6 were significantly higher than those in the control group[miR-155 mRNA(2-ΔΔCt):0.93±0.18 vs.0.17±0.03,IL-6(ng/L):73.84(33.44,429.00)vs.19.05(9.30,47.20),both P<0.05].Pearson correlation analysis showed that miR-155 and IL-6 levels were significantly positively correlated(r=0.782,P<0.01).With the extension of birth time,both WBC and NEUT gradually decreased in the two groups,and there were statistically significant differences in WBC and NEUT at each time point after birth,with counts significantly lower at 48 hours and 72 hours compared to 24 hours after birth(both P<0.05).The WBC of the observation group at 24,48 and 72 hours after birth was significantly lower than that of the control group(×109/L:7.85±2.44 vs.12.28±6.81 at 24 hours after birth,7.31±3.53 vs.10.98±7.91 at 48 hours after birth,4.97±2.05 vs.7.82±4.65 at 72 hours after birth,all P<0.05),NEUT in observation group was significantly lower than of control group at 24 hours and 48 hours after birth(×109/L:24 hours after birth was 4.13±1.93 vs.7.45±5.67,48 hours after birth was 3.96±2.64 vs.6.89±6.24,both P<0.05).Conclusion The expression level of miR-155 mRNA and IL-6 in very preterm neonates with preeclampsia is significantly up-regulated at the time of birth,and the inflammatory response of the body is disturbed,which has certain value for early assessment of the disease.

Objective:To investigate the clinical value of isolated fetal echogenic bowel (FEB) as an indicator for invasive prenatal diagnosis.Methods:This retrospective study enrolled 183 pregnant women who were diagnosed with isolated FEB and underwent invasive prenatal diagnosis in Fujian Maternity and Child Health Hospital from August 2013 to January 2021. Clinical data including the results of conventional karyotyping and chromosomal microarray analysis (CMA), cytomegalovirus (CMV) DNA loads in amniotic fluid and pregnancy outcomes were reviewed analyzed. Chi-square test was used for statistical analysis Results:Karyotyping was performed on all of the 183 fetuses and three (1.64%) aneuploidies (one case of trisomy 21, one trisomy 18 and one 47,XYY syndrome) were detected. One trisomy 21 and four pathogenic (P)/likely pathogenic (LP) copy number variation (CNV) were detected among 108 fetuses who received CMA. The detection rate of P/LP chromosomal abnormalities by CMA was higher than that by karyotyping, but there was no significant difference between them [4.63% (5/108) vs 0.93% (1/108), χ 2=1.54, P>0.05]. In addition, three cases of variants of uncertain significance (VOUS) were detected by CMA. CMV DNA loads of fetal cells in the amniotic fluid samples of the 166 cases were determined, and only one (0.6%) was positive (CMV DNA up to 7.01×10 6 copies/ml), and no abnormalities were found in karyotype analysis and CMA detection. A total of 176 cases were followed up, and among them only one case of intrauterine infection and seven cases (three aneuploidies and four P/LP CNV) of chromosomal abnormalities were terminated after genetic counseling. Three fetuses with VOUS and other 165 fetuses without chromosomal abnormalities had a good prognosis after birth. Conclusions:Isolated FEB may be the abnormal ultrasound finding in fetuses with chromosomal abnormalities or CMV infection. Prenatal genetic testing and the exclusion of intrauterine infection are important for management during pregnancy and prognosis assessment of FEB.

Objective:To explore the application of effect of healthcare failure mode and effect analysis (HFMEA) in emergency waiting risk management.Methods:From May 2020 to April 2021, totally 87 902 emergency waiting patients from the First Affiliated Hospital of Anhui Medical University were assigned to control group by cluster sampling method. From May 2021 to April 2022, 80 594 emergency waiting patients were assigned to observed group. The patients in the control group received routine emergency waiting of itinerant management mode. In contrast, the patients in the observed group received emergency waiting risk management mode based on HFMEA. The process risk priority number (RPN) and waiting risk management index between two groups were compared.Results:The mean RPN of the observed group was (98.48 ± 8.27) points, significantly lower than that of the control group (251.27 ± 16.95) points. The nurses′ pre-identification rates of changes in the condition and adverse reaction in the observed group were 10.77%(8680/80 594) and 13.37%(10 775/80 594), which were higher than those in the control group, 5.77%(5072/87 902) and 8.12%(7134/87 902), the differences were statistically significant ( χ2 values were 1402.32 and 1221.66, all P<0.05). Conclusions:The application of HFMEA to optimize the emergency waiting management process can effectively reduce the risk of emergency waiting and improve the quality of emergency waiting management.

OBJECTIVE: To analyze the intrauterine phenotype and genotype of eight fetuses carrying a 16p11.2 microdeletion. METHODS: 5100 fetuses undergoing routine prenatal diagnosis were subjected to single nucleotide polymorphism-based microarray (SNP-array) analysis. Fetuses harboring a 16p11.2 microdeletion were analyzed for their ultrasonographic characteristics. RESULTS: Eight fetuses were found to harbor a microdeletion in the 16p11.2 region. Among these, six had a typical 500-600 kb deletion, while the remaining two had an atypical 220 kb deletion at the distal part of 16p11.2. Four fetuses showed vertebral malformations, two had mild left ventriculomegaly, one had hydrocephalus, and one had pulmonary valve stenosis with regurgitation. The parents of five fetuses have accepted pedigree verification, and the results confirmed that the 16p11.2 microdeletions carried by fetuses all had a de novo origin. CONCLUSION The intrauterine phenotypes of fetuses carrying a 16p11.2 microdeletion may be variable, and the deletion can be effectively detected with the SNP-array assay.
Chromosome Deletion ; Female ; Fetus ; Genetic Testing ; Humans ; Phenotype ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To analyze the ultrasonographic phenotype and result of genetic testing in six fetuses carrying a 17q12 microdeletion. METHODS: Chromosomal microarray analysis (CMA) was carried out for 6200 pregnant women undergoing prenatal diagnosis from December 2016 to May 2021. RESULTS: CMA has identified 6 fetuses with a microdeletion in the 17q12 region, which spanned approximately 1.4 Mb and encompassed at least 13 OMIM genes. All fetuses have shown bilateral renal parenchymal echo enhancement. Four fetuses also had other ultrasonographic phenotypes. The parents of 4 fetuses had refused parental verification, whilst the remaining two fetuses were confirmed to be de novo in origin. CONCLUSION The prenatal ultrasonographic phenotype of 17q12 microdeletion is mainly enhanced bilateral renal parenchymal echos. CMA can facilitate detection of the 17q12 microdeletion.
Female ; Humans ; Pregnancy ; Genetic Testing ; Phenotype ; Fetus/diagnostic imaging* ; Prenatal Diagnosis ; Parents

ObjectiveTo explore the effect of Suanzaoren Tang combined with Ziwu Liuzhu acupuncture on the vertebral artery hemodynamics， inflammatory cytokines， and neurotrophic factors in the patients with cervical insomnia with syndrome of deficiency of both heart and spleen. MethodThe random number table method was employed to assign 164 patients with cervical insomnia with syndrome of deficiency of both heart and spleen treated in the First Clinical Medical School of Guangzhou University of Chinese Medicine from January 2018 to June 2021 into a control group and an observation group. The control group was orally administrated with 1-2 mg estazolam tablets before bed for 4 weeks， and the observation group with Suanzaoren Tang combined with Ziwu Liuzhu acupuncture for 4 weeks. The therapeutic efficacy and safety were observed. The Pittsburgh Sleep Quality Index （PSQI） score， polysomnography monitoring results， hemodynamics parameters of vertebral artery， and serum levels of inflammatory cytokines and neurotrophic factors were compared before and after treatment. ResultExcept 4 dropouts， the remaining 160 patients were included in this study， with 80 patients in each group. The observation group had higher total effective rate than the control group ［92.50% （74/80） vs. 80.00% （64/80）， χ²=5.270， P<0.05］. Compared with that before treatment， the therapies in both groups decreased the PSQI score， sleep latency time， awakening time， awakening times， serum levels of interleukin-1β （IL-1β）， C-reactive protein （CRP）， and tumor necrosis factor-α （TNF-α） （P<0.01）. Meanwhile， they increased the proportion of rapid-eye-movement （REM） sleep， the diastolic blood flow velocity （Vd）， systolic blood flow velocity （Vs）， and mean blood flow velocity （MFV） of vertebral artery， as well as the serum levels of brain-derived neurotrophic factor （BDNF） and glial cell-derived neurotrophic factor （GDNF） （P<0.05， P<0.01）. Moreover， the observation group had lower PSQI score， sleep latency time， awakening time， awakening times， and serum IL-1β， CRP， and TNF-α levels （P<0.01） and higher proportion of REM sleep， Vd， Vs， MFV of vertebral artery， and serum BDNF and GDNF levels （P<0.05， P<0.01） than the control group. ConclusionZiwu Liuzhu acupuncture combined with Suanzaoren Tang can improve blood circulation of vertebral artery， reduce the serum levels of inflammatory cytokine， and increase the serum levels of neurotrophic factors to improve the sleep quality of the patients with cervical insomnia with syndrome of deficiency of both heart and spleen.

OBJECTIVE: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). METHODS: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. RESULTS: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. CONCLUSION Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.
22q11 Deletion Syndrome/diagnostic imaging* ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics* ; Female ; Fetus ; Genetic Testing ; Humans ; Pregnancy ; Prenatal Diagnosis ; Ultrasonics