Acute myeloid leukemia (AML) is a disease caused by abnormal cloning of hematopoietic stem cells in the bone marrow, which leads to accumulation of a large number of abnormally differentiated myeloid cells. It is difficult to cure by traditional treatment. The successful application of chimeric antigen receptor T cell (CAR-T) immunotherapy indicates that the treatment of hematological tumors has entered a new stage of precision immunotherapy. However, CAR-T immunotherapy has been found to have many problems in clinical applications, including long treatment cycle, expensive prices, off-target effects, cytokine release syndrome, etc. Therefore, it is necessary to expand the application of CAR or adopt improved measures to enhance the therapeutic effect. This article reviews the new strategies for genetic engineering modification of CAR immune cells and the research progress and application of in situ programming to generate CAR-T, and besides, briefly introduces the new methods about the delivery of gene drugs in vivo, aiming to provide new ideas and theoretical basis for expanding and improving the application of precision immunotherapy in AML.

Objective:To investigate the effect of prenatal dexamethasone on short-term outcomes and long-term neurological development in late preterm infants with twin pregnancy.Methods:A total of 315 pregnant women with twin pregnancy and their preterm infants who delivered in Peking University Third Hospital from January 2019 to December 2022 were retrospectively analyzed. The clinical data of pregnant women and preterm infants were collected. They were divided into non-medication group (93 pregnant women and 186 preterm infants), medication after 34 weeks group (123 pregnant women and 246 preterm infants), and medication before 34 weeks group (99 pregnant women and 198 preterm infants). Short-term outcomes of preterm infants were analyzed, including the incidence of neonatal respiratory distress syndrome (NRDS), wet lung, hypoglycemia, neonatal septicemia, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and neonatal necrotizing enterocolitis (NEC). "Ages and Stages Questionnaire-Third Edition (ASQ-3) scale" was used to follow up the late neurological development of preterm infants at the corrected age of 6-54 months, and the level of neurological development was compared.Results:(1) General conditions: the gestational age at delivery in the non-medication group [36.1 weeks (35.6, 36.6 weeks)] was later than that in the medication after 34 weeks group [36.1 weeks (35.2, 36.4 weeks)] and medication before 34 weeks group [35.2 weeks (34.2, 36.2 weeks)] groups, and the differences were statistically significant (all P<0.05). After correcting for gestational age, there was no significant difference in birth weight among the three groups ( H=3.808, P=0.149). There were no significant differences in gender and the proportion of small for gestational age among the three groups (all P>0.05). (2) Short-term outcome: the incidence of wet lung was 7.0% (13/186), 11.0% (27/246) and 16.2% (32/198) in the non-medication group, medication after 34 weeks group and medication before 34 weeks group, respectively, and the difference was statistically significant ( P=0.018). There were no significant differences in the incidence rates of NRDS, hypoglycemia, sepsis, IVH, BPD, and NEC among the three groups (all P>0.05). Logistic regression analysis with gestational age and newborn birth weight as confounding factors showed that early gestational age ( OR=0.884, 95% CI: 0.837-0.933, P<0.001) and increased incidence of selective intrauterine growth restriction type I ( OR=2.967, 95% CI: 1.153-7.639, P=0.024) could both lead to an increased incidence of wet lung. (3) Long-term outcomes: a total of 109 pregnant women completed the follow-up, and 218 preterm infants with a corrected age of 6-54 months at the end of follow-up were enrolled, including 86 cases in the non-medication group, 66 cases in the medication after 34 weeks group, and 66 cases in the medication before 34 weeks group. There were no significant differences in the scores of communication, gross motor, fine motor, problem solving and personal-social among the three groups (all P>0.05). Conclusion:Prenatal administration of a single course of dexamethasone does not affect the neonatal birth weight and short-term outcomes of twin late preterm infants, and has no adverse effect on the neurological development of twin late preterm infants with a corrected age of 6-54 months.

Objective:To explore the produced-radiation brain damage in simulated solar particle events and to provide evidence for health risk assessment of radiation from manned deep space exploration.Methods:According to the main characteristics of solar particle events, mice were treated with total body irradiation (TBI) with 90 MeV protons in a dose range from 0.1 to 2 Gy, with irradiation dose of 0, 0.1, 0.3, 0.5, 1, 2 Gy, respectively. At 3 and 7 d after irradiation, the behavior of mice was examined using balance beam tests, rotarod tests, and new object recognition tests. Then, the density of dendritic spines and the number of Nissl bodies in the hippocampus were measured using Golgi and Nissl staining. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and neurotransmitter content in brain tissue were detected using the WST-8 method, TBA method, and high pressure liquid chromatography (HPLC), respectively. Besides, cell apoptosis was determined using the TUNEL method, and the dose-response relationship, a function of dose change with damage index, was analyzed using linear and linear square fitting method. Finally, the minimum radiation dose causing a significant change in all indicators of brain damage was determined as the brain damage threshold.Results:Compared to the control group, 1 Gy proton irradiation result ed in a significant decrease in the density of filopod dendritic spines ( t = 1.82, 2.30, P < 0.05) and a significant increase in abnormal Nissl bodies in the CA1 region ( t = 2.44, 3.77, P < 0.05). At 3 and 7 d after irradiation, as well as a significant increase in the DA ( t = 2.52, P<0.05) and Glu contents ( t = 4.04, P < 0.05) on day 7. In contrast, 2 Gy proton irradiation result ed in a decrease in SOD activity on day 3 ( t = 3.44, P < 0.05), and an increase in the MDA content ( t = 1.90, 2.14, P < 0.05), hippocampal cell apoptosis (t = 3.91, 3.54, P < 0.05), and 5-HT levels ( t = 2.81, 2.69, P < 0.05), together with a decrease in climbing time in the rotarod tests ( t = 2.85, 2.64, P<0.05) and propensity to recognize new objects ( t = 2.87, 2.84, P < 0.05) on days 3 and 7. Furthermore, a dose-response relationship was observed in the dose range from 0.1 to 2 Gy ( R2=0.74-0.99). Conclusions:The dose threshold of 90 MeV protons inducing brain damage in mice is inferred to be 1 Gy, and 14 dose-response models are developed, providing a biological basis for organ dose capping and risk assessment of crew experiencing short-term deep space flights.

Objective:To evaluate the outcome of laser coagulation under fetoscope for placental chorioangioma (CA).Methods:The clinical data of three pregnant women with giant CA treated by laser coagulation under fetoscope in Peking University Third Hospital from January 2018 to December 2020 were analyzed retrospectively. Relevant articles up to September 2022 were retrieved from Wanfang Database, China National Knowledge Infrastructure and PubMed, and the clinical data of all patients were retrospectively summarized. Indications and intervention effects of fetoscopic laser therapy were analyzed. Descriptive statistics was used to describe the data.Results:Thirteen patients were involved in this study including 10 cases retrieved from the databases. The average age of the pregnant women was (30.3±6.2) years old. There were 12 cases of single pregnancy and one case of twin pregnancy (monochorionic diamnionic twin pregnancy). Except for cases for which data were not available in the literatures, at the diagnosis of CA, the average gestational age was (19.9±4.5) weeks ( n=7) and the average maximum diameter of the mass was (6.1±4.1) cm ( n=6). The patients underwent fetoscopic laser therapy at an average gestational age of (25.0±2.0) weeks ( n=13) with the average maximum tumor diameter of (7.6±2.8) cm ( n=9). After treatment, the amniotic fluid volume of three cases decreased to normal. In one case, the amniotic fluid volume decreased but was still above the upper limit of the normal range. Moreover, the maximum tumor diameter decreased in four cases; the peak systolic velocity of the fetal middle cerebral artery decreased to normal in one case; fetal heart function became normal in two cases and fetal edema was relieved in one case. Among the three patients treated in our hospital, the blood supply of CA disappeared after treatment. Intrauterine fetal death occurred in two cases. The other 11 patients gave birth to live babies at the gestational age of (36.6±3.8) weeks with five through cesarean section (5/11), five through vaginal delivery (4/11) and two not reported. The birth weight of the neonates was (2 712±1 023) g and all of them survived. The gender of five neonates were reported and all were females, two of them were monochorionic diamnionic twins. No abnormality was found in the three neonates delivered in our hospital during a six-month follow-up. No abnormality was reported in the other neonates during ten days to six months of follow-up. Conclusions:Fetoscopic laser coagulation may help reduce the size of CA, decrease complications and improve pregnancy outcomes.

Renal hematuria is caused by glomerular damage and basement membrane rupture due to coagulation dysfunction， ischemia and hypoxia， and immune function damage， resulting in red blood cells exuding through glomerular filtration membrane and excreting with urine. It is mainly manifested as microscopic and macroscopic hematuria. Among them， microscopic hematuria is characterized by microscopic urine sediment examination， there are three or more red blood cells per high-power microscopic field. Traditional Chinese medicine （TCM） believes that the pathogenesis of renal hematuria always belongs to ''asthenia in origin and sthenia in superficiality''， and ''asthenia in origin'' is caused by the deficiency of the three viscera of the lung， spleen， and kidney， while ''sthenia in superficiality'' is caused by the combination of dampness and blood stasis and the external disturbance of wind pathogens. The key pathogenesis features are ''deficiency， dampness， heat， blood stasis， and wind''. After consulting the TCM literature related to renal hematuria， the author found that the common syndrome types of renal hematuria in clinical practice were the deficiency of both Qi and Yin， the deficiency of both Yin and fire， the unsteadiness of kidney Qi， the deficiency of spleen and kidney Yang， the wind heat hurting the collateral， the dampness-heat blocking， and the blood stasis and internal resistance. The commonly used classical or temporal prescriptions included Shenqi Dihuangtang（参芪地黄汤）， Zhibai Dihuangtang（知柏地黄汤）， Wubi Shanyaowan（无比山药丸）， Jisheng Shenqiwan（济生肾气丸）， Sishenwan（四神丸）， Yinqiaosan（银翘散）， Bazhengsan（八正散）， Sanrentang（三仁汤）， Xuefu Zhuyutang（血府逐瘀汤）， Danggui Shaoyaosan（当归芍药散）， Xiaoji Yinzi（小蓟饮子）， Buzhong Yiqitang（补中益气汤）， et al. Self prepared prescriptions mainly include Tongluo Ningxue prescription （通络宁血方）， Qingre Zhixue prescription（ 清热止血方） and Wuteng Tongluo drink （五藤通络饮）. The traditional Chinese medicine is commonly used for the treatment of Xueniaoling granules（血尿灵冲剂）， Xueniaoan capsules（血尿安胶囊）， Ningmitai capsules（宁泌泰胶囊）， Huangkui capsules（黄葵胶囊） and Yishen nixuexiao granules（益肾溺血消颗粒）， which constantly enriched the treatment of renal hematuria. The combination of TCM and western medicine has obvious advantages. The treatment of renal hematuria in clinical practice often combines with modern medical methods， which has a good therapeutic effect on the improvement of symptoms and indicators of renal hematuria. At present， many doctors have made in-depth exploration on the etiology， pathogenesis， and clinical treatment of renal hematuria， but few scholars have made detailed induction and collation in recent years. Therefore， the author has collated the clinical data on the treatment of renal hematuria with TCM in the past ten years， and reviewed it from the aspects of etiology， pathogenesis， and clinical research， to provide useful references for clinical intervention and delay the progress of renal disease.

【Objective】 To explore the role and mechanism of TRPC6 in apoptosis of glomerular mesangial cells (HBZY-1) induced by endoplasmic reticulum stress (ERS). 【Methods】 The experiment groups were classified as follows: normal control (NC), thapsigargin (TG), TG+SKF96365, and TG+TRPC6 siRNA groups. Transcription and protein expressions of TRPC6 and ERS related proteins (GRP78 and Caspase12) were detected by qRT-PCR and Western blotting. Additionally, cell apoptosis was measured by flow cytometry and Hoechst33258. Finally, Fluo-4 AM Ca²⁺ imaging technique was used to determine changes of intracellular calcium ( [Ca²⁺] i) by laser scanning confocal microscope. 【Results】 Morphological changes of apoptotic cells were characterized by nuclear enrichment or nuclear fragmentation, and the apoptosis rate was increased after TG stimulation. The expressions of TRPC6 and ERS related proteins (GRP78 and Caspase12) were elevated in TG group compared with NC group (P<0.05). Pre-incubation of HBZY-1 cells with SKF96365 and TRPC6 siRNA decreased cell apoptosis (P<0.05). The entry of [Ca²⁺] i also increased after TG stimulation (P<0.05). The expressions of TRPC6, GRP78 and Caspase12 were downregulated compared with TG group after treatment with SKF96365 and TRPC6 siRNA accompanied by decreased [Ca²⁺] i (P<0.05). 【Conclusion】 Taken together, this study suggests that inhibition of TRPC6 can alleviate TG-induced HBZY-1 cell apoptosis.

【Objective】 To explore the role and mechanism of TRPC in promoting extracellular matrix (ECM) deposition in rat glomerular mesangial cells (HBZY-1). Methods Immunofluorescence staining was performed to observe the distribution and expression of TRPC1 and TRPC6 in HBZY-1 cells. After AngⅡ stimulation, qRT-PCR and Western blotting were used to detect the mRNA and protein expressions of Gαq/PLCβ4/TRPC signaling pathway main proteins and ECM deposition indicators (α-SMA, collagenⅢ and fibronectin). By silencing the expressions of TRPC1 and TRPC6 by RNA interference, the expressions of ECM deposition indicators were detected. Changes in [Ca²⁺]i influx were determined through Fluo-4AM Ca²⁺ imaging. 【Results】 Both TRPC1 and TRPC6 were expressed in HBZY-1, and were mainly located in cell membrane and cytoplasm. After AngⅡ stimulation, Gαq/PLCβ4/TRPC signaling pathway was activated, and the mRNA and protein expressions of Gαq, PLCβ4, TRPC1 and TRPC6 were all increased (P<0.05). [Ca²⁺]i influx also increased (P<0.01), and the mRNA and protein expressions of ECM deposition indicators (α-SMA, ColⅢ and Fn) were upregulated (P<0.05). Silencing the expressions of TRPC1 and TRPC6 by RNA interference led to decreased [Ca²⁺]i influx (P<0.05), and downregulated mRNA and protein expressions of ECM deposition indicators in HBZY-1 cells (P<0.05). The results suggested that inhibition of TRPC expressions could inhibit AngⅡ induced ECM deposition in HBZY-1 cells, which might be associated with decreased [Ca²⁺]i influx. 【Conclusion】 TRPC may be a novel therapeutic target of renal fibrosis.

Objective:To investigate the short- and long-term outcomes of fetuses with selective fetal growth restriction (sFGR).Methods:A retrospective study was conducted on monochorionic diamniotic (MCDA) twins with sFGR admitted to the Neonatal Intensive Care Unit of Peking University Third Hospital from September 2017 to December 2019. MCDA neonates delivered during the same period without significant complications were selected as the control group. MCDA twins with sFGR were divided into type Ⅰ, Ⅱ, and Ⅲ groups and then further divided into the larger and the smaller fetus subgroups according to the birth weight. These children were followed up by telephone at 2-3 years old. Height-for-age and weight-for-age Z-scores were calculated. Ages and Stages Questionnaire-Third Edition (ASQ-3) was used to determine comprehensive development. Independent sample t-test, one-way analysis of variance, non-parameter test, and Chi-square test (or rank-sum test) were used for statistical analysis. Results:(1) A total of 116 pregnant women with sFGR (232 neonates) were enrolled in this study. There were 43, 40, and 33 mothers and 86, 80, and 66 newborns in type Ⅰ, Ⅱ, and Ⅲ groups, respectively. The control group included 31 pregnant women and 62 neonates. The gestational age at onset of sFGR was younger in the type Ⅱ and Ⅲ groups than in type Ⅰ group [(23.8±4.8) and (24.1±3.1) vs (27.0±6.1) weeks, F=5.19, P<0.05; all P<0.017 during pairwise comparisons]. (2) The incidence of sepsis and treatment abandonment/death in neonates in type Ⅱ and Ⅲ groups were higher than those in type Ⅰ and control groups [neonatal sepsis: 11.3% (9/80) and 6.1% (4/66) vs 2.3% (2/86) and 0.0% (0/62), χ2=6.30, P=0.001; death or treatment abandonment rate:13.8% (11/80) and 10.6% (7/66) vs 3.5% (3/86) and 0.0% (0/62), χ2=4.68, P=0.003; all P<0.017 during pairwise comparisons]. In cases with type Ⅱ or type Ⅲ sFGR, the risk of digestive system diseases was significantly higher in the smaller fetus group than in the larger fetus group [type Ⅱ: 46.2% (37/80) vs 38.7% (31/80), χ2=16.72; type Ⅲ: 47.0% (31/66) vs 34.8% (23/66), χ2=39.69; both P<0.001], while the rate of respiratory system diseases was lower in the smaller fetus group [type Ⅱ: 35.0% (28/80) vs 45.0% (36/80), χ2=36.85; type Ⅲ: 37.9% (25/66) vs 45.4% (30/66), χ2=12.55; both P<0.001]. The incidence of neonatal sepsis in smaller fetuses was higher than that in larger ones in type Ⅱ sFGR [7.5% (6/80) vs 3.7% (3/80), χ2=4.68, P=0.034]. The incidence of neurological complications in larger fetuses was higher than that in smaller ones in type Ⅲ sFGR [15.1% (10/66) vs 4.5% (3/66), χ2=5.72, P<0.001]. (3) In type Ⅱ group, seven neonates died (one case of cerebral hemorrhage, two cases of gastrointestinal perforation, two cases of septic shock, and two cases of necrotizing enterocolitis), and four cases withdrew the treatment. In type Ⅲ group, four neonates died (two cases of necrotizing enterocolitis, one case of gastrointestinal perforation, and one case of cerebral hemorrhage), and three cases withdrew from the treatment. (4) Totally, 71 children in type Ⅰ, 61 in type Ⅱ, and 58 in type Ⅲ group were followed up at the age of 2-3. Children with type Ⅱ or type Ⅲ sFGR lagged behind those in type Ⅰ group and control group in physical growth [ M ( P25- P75), Z-scores:－0.46 (－0.87-0.42),－0.35 (－0.62-0.71), 0.05 (－0.61-0.51), and 0.14 (－0.57-0.75); H=6.20, P=0.001]. In type Ⅱ and Ⅲ groups, the smaller fetuses lagged the larger fetuses in physical growth at 2-3 years of age. ASQ-3 scores in communication, gross motor, fine motor, problem-solving and personal-social areas were all lower in type Ⅱ and Ⅲ groups than in type Ⅰ and control groups. ASQ-3 scores in the five dimensions of the smaller fetuses in the type Ⅱ group were lower than those of the larger fetuses. In the type Ⅲ group, the smaller fetuses had lower ASQ-3 scores in communication and gross motor than the larger ones [communication ability: (42.6±18.8) vs (56.4±9.4) scores, t=19.63, P<0.001; gross motor: (45.5±19.7) vs (54.5±9.7) scores, t=12.64, P=0.003]. Conclusion:The neonatal morbidity is significantly increased in type Ⅱ and Ⅲ sFGR, and babies lagged others in height, weight, and ASQ-3 score at 2-3, which is worthy of early attention.

Objective:To analyze the clinical value of noninvasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies.Methods:A total of 164 VT pregnancies that underwent NIPT in Peking University Third Hospital from January 2017 to December 2020 were enrolled. Gestational age at onset of vanishing, results of NIPT and invasive prenatal diagnosis, blood sampling time points, and pregnancy outcomes were retrospectively analyzed using two independent samples t test and Chi-square test. Results:(1) Of the 164 cases, six had positive results for NIPT, but negative results for karyotype analysis or single nucleotide polymorphism genotyping, with a false positive rate of 3.7% (6/164) for NIPT and all of them were delivered at term. Four pregnancies terminated in the second trimester, including two fetal malformation cases and one unexplained intrauterine death whose single nucleotide polymorphisms results are all normal and one inevitable abortion case due to premature rupture of membrane who refused amniocentesis. The other 154 women all gave birth to normal phenotype babies including 12 preterm ones. (2) The false-positive rate of NIPT was lower in VT pregnancies diagnosed at less than eight gestational weeks than those diagnosed after [1.5% (2/134) vs 13.3% (4/30), χ2=6.68, P=0.010]. The false-positive rate was 6.9% (4/58) in women diagnosed at or below eight weeks between the occurrence of VT and blood sampling and was 1.9% (2/106) in those with interval more than eight weeks, but without significant difference ( χ2=1.44, P=0.231). Conclusions:Although VT pregnancies exist false-positive results in NIPT, screening is still recommended based on fully informed consent to reduce unnecessary invasive prenatal diagnosis. The earlier the onset of VT, the lower the NIPT false positive rate, but whether extending the sampling interval would reduce the risk of false-positive needs further study.

Objective:To evaluate the effect of inhibition of interleukin-6 (IL-6) trans-signaling on sepsis-associated encephalopathy (SAE) in mice.Methods:Eighty healthy male C57BL/6J mice, aged 8-10 weeks, weighing 22-24 g, were divided into 4 groups using a random number table method: sham operation group (Sham group, n=10), SAE group ( n=35), SAE plus sgp130Fc group ( n=25) and sgp130Fc group ( n=10). Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized animals.Sham and sgp130Fc groups received no CLP.In group sgp130Fc and group SAE+ sgp130Fc, sgp130Fc 0.5 mg/kg was intraperitoneally injected at 1 h after sham operation or CLP.The survival rates, body weight and neurological function scores were recorded within 1-10 days after sham operation or CLP.Four mice in each group were selected at 24 h after sham operation or CLP to detect the expression of occlusin in hippocampus by Western blot.Five mice in each group were selected to measure cognitive function using Morris water maze test at day 4 after sham operation or CLP. Results:Compared with group Sham, the survival mice, body weight and neurological function scores on days 2-10 after CLP were significantly decreased, the expression of occludin was down-regulated, the frequency of crossing the original platform was decreased, and the time spent in target quadrant was shortened in group SAE ( P<0.05), and no significant change was found in the indexes mentioned above in group sgp130Fc ( P>0.05). Compared with group SAE, the survival rate and neurological function scores on days 3-10 after CLP were significantly increased, the expression of occludin was up-regulated, the frequency of crossing the original platform was increased, and the time spent in target quadrant was prolonged ( P<0.05), and no significant change was found in body weight in group SAE+ sgp130Fc ( P>0.05). Conclusions:Inhibition of IL-6 trans-signaling can reduce the damage to the blood brain barrier and SAE in mice.