1.Quality Evaluation of Naomaili Granules Based on Multi-component Content Determination and Fingerprint and Screening of Its Anti-neuroinflammatory Substance Basis
Ya WANG ; Yanan KANG ; Bo LIU ; Zimo WANG ; Xuan ZHANG ; Wei LAN ; Wen ZHANG ; Lu YANG ; Yi SUN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):170-178
ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics, and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography (UPLC) fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated, and 23 of them were identified and assigned. In 27 batches of Naomaili granules, the mass fractions of 14 components that were stachydrine hydrochloride, leonurine hydrochloride, calycosin-7-O-glucoside, calycosin,tanshinoneⅠ, cryptotanshinone, tanshinoneⅡA, ginsenoside Rb1, notoginsenoside R1, ginsenoside Rg1, paeoniflorin, albiflorin, lactiflorin, and salvianolic acid B were found to be 2.902-3.498, 0.233-0.343, 0.111-0.301, 0.07-0.152, 0.136-0.228, 0.195-0.390, 0.324-0.482, 1.056-1.435, 0.271-0.397, 1.318-1.649, 3.038-4.059, 2.263-3.455, 0.152-0.232, 2.931-3.991 mg∙g-1, respectively. Multivariate statistical analysis showed that paeoniflorin, ginsenoside Rg1, ginsenoside Rb1 and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them, salvianolic acid B and ginsenoside Rb1 had strong anti-inflammatory activity, with IC50 values of (36.11±0.15) mg∙L-1 and (27.24±0.54) mg∙L-1, respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out, and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.
2.Disease burden and changing trend in tracheal, bronchus, and lung cancer attributable to air pollution globally and in China and the United States from 1990 to 2021
Shoucai HU ; Chenglong YANG ; Lingling ZHANG ; Fu LI ; Yanan ZHANG ; Bin LIU ; Qingxin LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):97-104
Objective To systematically analyze the spatiotemporal distribution characteristics and epidemiological trends of tracheal, bronchus, and lung cancer (TBL) disease burden attributed to air pollution globally and in China and the United States from 1990 to 2021, and to assess the patterns of disease burden changes from 2022 to 2031 based on predictive models, providing a scientific basis for formulating targeted TBL prevention and control strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we analyzed the disease burden data of TBL attributed to air pollution globally and in China and the United States from 1990 to 2021. R Studio 4.3.2 software was used to analyze the corresponding trends and the Bayesian age-period-cohort (BAPC) prediction model was used to predict the status of the disease burden of TBL attributed to air pollution in the world and in China and the United States from 2022 to 2031. Results In 2021, China had the highest number of deaths and disability-adjusted life years attributed to air pollution (211 400 patients and 4.8947 million person-years), followed by the United States (6 000 patients and 124 300 person-years). The age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) of TBL due to air pollution in the world and in China and the United States showed a decreasing trend. From 1990 to 2021, the ASMR and ASDR of TBL in China due to air pollution were much higher than those in the United States and the global average. In terms of gender, from 1990 to 2021, the disease burden of male patients with TBL attributed to air pollution was much higher than that of female patients. The BAPC prediction model showed that from 2022 to 2031, the ASMR and ASDR of TBL attributed to air pollution showed an upward trend globally, while they showed a downward trend in China and the United States. Conclusion Over the past 30 years, the air pollution-related TBL disease burden in the world and in China and the United States has continued to decline, but China's disease burden is still significantly higher than the global average. The disease burden in men far exceeds that in women, with men and the population aged ≥50 years being high-risk groups. In the future, the global disease trend may reverse and rise, while China and the United States are expected to continuously decline. However, precise prevention and control for high-risk groups remains a key challenge.
3.Ectopic expression of hemoglobin subunits enhances the in vitro cytotoxicity of CAR-T cells against tumor cells under hypoxic conditions
YANG Jianxun1,2 ; ZHENG Rui3 ; LIANG Sixin3 ; PAN Jie4 ; LI Yanlong5 ; ZHAI Chenxi5 ; ZHAO Xiaojuan2 ; WANG Pengju3 ; DONG Hao4 ; YAN Bo2 ; SUN Zhihong1 ; YANG Angang3
Chinese Journal of Cancer Biotherapy 2026;33(3):233-242
[摘 要] 目的:探讨异位表达血红蛋白亚基(HBA/HBB)对缺氧条件下嵌合抗原受体T细胞(CAR-T细胞)功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法:全基因合成技术合成靶向HER2的CAR序列,构建共表达HBA或HBB的CAR慢病毒载体,包装慢病毒后感染人原代T淋巴细胞,制备异位表达HBA/HBB的CAR-T细胞,命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况,采用细胞计数板计数检测细胞增殖水平,通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力,qPCR检测CAR-T细胞中缺氧诱导因子-1α(HIF-1α)表达水平,利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果:不同细胞构建的实体瘤模型均存在明显缺氧情况,且CAR-T细胞浸润水平与缺氧程度呈显著负相关(P < 0.000 1)。HBA CAR-T与HBB CAR-T构建成功(阳性率 > 60%),相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降,增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞(均P < 0.05)。HBA CAR-T与HBB CAR-T内HIF-1α表达降低(均P < 0.001),且缺氧程度显著降低(均P < 0.001)。结论:异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。
4.Comparison between ultrafiltration and dextran gel method in the purification of Tfn/PCL micelles
Lingbo YU ; Yadong ZHANG ; Rui XU ; Yuyu SUN ; Huiyun WANG ; Jinjin YANG ; Yanan CUI
Acta Universitatis Medicinalis Anhui 2026;61(2):258-263
ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 (C6) was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction, resulting in two types of micelles: Tfn/PCLH and Tfn/PCLL. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively, and the efficiency of the two methods, along with the purity of the final micelles, was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm, and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCLL and Tfn/PCLH, respectively. The micelle population was monodisperse. The purification results showed that, for the ultrafiltration method, after two and one rounds of purification, the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCLH and Tfn/PCLL, respectively. For the dextran gel filtration method, the Tfn/C6 ratio reached 23.7 for the Tfn/PCLH group after two rounds of purification. However, for the Tfn/PCLL group, the Tfn/C6 ratio increased during four rounds of dextran gel purification, and a significant difference (P = 0.042 4) was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method, the Tfn density of Tfn/PCLH and Tfn/PCLL were 94.9% and 13.8%, respectively. For the dextran gel filtration method, the density of the two micelles were 95.6% and 14.4%, respectively. For Tfn/PCLL group, the density results revealing a statistically significant difference (P=0.000 2). ConclusionThe purification efficiency of the two methods is comparable. However, the purity of the final micelles shows a significant difference, with the dextran gel filtration method resulting in higher purity, particularly for the Tfn/PCLL micelles.
5.Protection Cartilage Injury and Alleviate Knee Osteoarthritis Pain of Electroacupuncture Combined with Massage in Osteoarthritis Rat Model
Yang LIU ; Xiaona XUE ; Yanan LYU ; Sheng GUO ; Peidong WEI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(1):292-300
Objective The protective effect and molecular mechanism of electroacupuncture combined with massage on cartilage damage in knee Osteoarthritis rats were explored.Methods 50 SD rats were selected and divided into a control group,a model group,an electroacupuncture group,a massage group,and an electroacupuncture+massage group of 10 rats each using an odd even number method.The rats in the control group were not treated with modeling,and the rats in the other groups were injected with Papain into the articular cavity to build the right knee Osteoarthritis(KOA)model.The massage and electroacupuncture groups were intervened with electroacupuncture and massage for 2 weeks.The improved Le-quesne MG scale was used to evaluate the behavioral performance of rats.The pressure pain value and heat pain threshold of rats before and after intervention were calculated.After eight weeks,the rats were euthanized and abdominal aortic blood was collected.The serum levels of pain mediators(K+),5-hydroxytryptamine(5-HT),and dopamine(DA)were measured by ELISA in each group of rats.The right knee joint of rats was taken for HE staining Mankin score,TUNEL chondrocyte apoptosis analysis.Toluidine blue staining was used to observe the changes of cartilage matrix polysaccharide;Western blot was used to detect the concentration and expression of cartilage matrix factor type Ⅱ collagen(Collagen Ⅱ),C-terminal peptide(CTX Ⅱ),type Ⅱ collagen C-precursor peptide(CPⅡ),apoptosis related proteins Bax,Bcl-2,Cleared caspase-3,YAP,p-YAP in the knee joint tissues of rats in each group.Results After the establishment of the KOA model,the Lequesne MG score of rats increased significantly(P<0.05).Compared with the model group,the Lequesne MG scores of rats in the electroacupuncture group and massage group decreased significantly(P<0.05).The combination of the two can further reduce the Lequesne MG score significantly(P<0.05).Compared with the control group,the pain threshold(TWL,MWT)of the model group was downregulated significantly,and the levels of serum pain factors(K+,DA,5-HT)were upregulated significantly(P<0.05).Compared with the model group,the pain thresholds(TWL,MWT)of the electroacupuncture group and the massage group were upregulated significantly,while the levels of serum pain factors(K+,DA,5-HT)were downregulated significantly(P<0.05).The combination of the two reflected the highest pain threshold(TWL,MWT)and the lowest serum pain factor(K+,DA,5-HT)levels.The model group rats had significant joint cartilage fissures,cartilage matrix staining and staining area decreased,and Markin score and cell apoptosis ability were improved(P<0.05).Compared with the model group,the arrangement degree of the cartilage layer,staining degree of the cartilage matrix,and staining area of the electroacupuncture group and massage group were all improved,while the Markin score and cell apoptosis rate all decreased significantly(P<0.05).The combination can further reduce the Markin score and the degree of chondrocyte apoptosis(P<0.05).Compared with the control group,the expression of Collagen Ⅱ,CPⅡ,Bcl-2,and p-YAP proteins in the model group decreased significantly,while the expression of CTX Ⅱ,Bax,and Cleared caspase-3 proteins increased significantly(P<0.05).Conclusion The combination of electroacupuncture and massage intervention can significantly improve the pathological state of cartilage injury in rats with osteoarthritis,reduce knee joint pain,inhibit chondrocyte apoptosis,and play a protective role in cartilage injury.Its molecular mechanism may be related to the activation of Hippo YAP signaling pathway,which is worth further research in clinical practice.
6.Diagnostic value of contrast-enhanced ultrasound time-intensity curve for the main pathological features of cervical cancer and its correlation
Fang FENG ; Yanan ZHI ; Yang WANG ; Pan LIU ; Jiawen PENG ; Li’na ZHAO
Chinese Journal of Endocrine Surgery 2025;19(4):601-606
Objective:To study the diagnostic value and correlation of contrast-enhanced ultrasound time-intensity curve in the main pathological features of cervical cancer.Methods:From August 2021 to August 2023, 100 patients with cervical cancer and 100 patients with benign cervical tumors examined in Dingzhou People’s Hospital were selected for study. Patients with benign cervical tumors were included in the control group, and patients with cervical cancer were included in the observation group.The two groups of patients were examined by PHILIPS EPIQ7 C color Doppler ultrasound diagnostic instrument and PHILIPS EPIQ5 color Doppler ultrasound diagnostic instrument to obtain the quantitative parameters of the time-intensity curve of the two groups. The bivariate Spearman correlation test was used to analyze the main pathological features of cervical cancer patients (lesion diameter, pathological type, vascular invasion, lymph node metastasis, differentiation degree, clinical stage) and the correlation between radiotherapy and chemotherapy and the acquisition of time-intensity curve. The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of the time-intensity curve.Results:The time to peak (TTP) value of the cervical cancer group was lower than that of the control group, and the peak intensity (PI) and maximum peak intensity ratio (PI/PIc) values were higher than those of the control group, the differences were statistically significant ( P<0.05). Compared with patients with non-squamous cell carcinoma, vascular invasion < 1/2, no lymph node metastasis, moderate to high differentiation, stage I-II, and after radiotherapy and chemotherapy, patients with squamous cell carcinoma, vascular invasion ≥ 1/2, lymph node metastasis, low differentiation, stage III-IV, and before radiotherapy and chemotherapy had lower TTP values, higher PI and PI/PIc values, and the differences were statistically significant ( P<0.05). Pathological type, vascular invasion, lymph node metastasis, differentiation degree and clinical stage were negatively correlated with TTP, and positively correlated with PI and PI/PIc ( P<0.05) .Chemoradiotherapy was positively correlated with TTP, and negatively correlated with PI and PI/PIc ( P<0.05). The sensitivity and specificity of combined detection of time intensity curve were higher than those of TTP, PI, PI/Ic, area under curve (AUCTC) and mean transit time (MTT), and the differences were statistically significant ( P<0.05). The AUC values of combined detection of TTP, PI, PI/PIc and time intensity curve were all > 0.85, and the diagnostic value was high. Conclusions:The time-intensity curve of contrast-enhanced ultrasound is closely related to the main pathological features of cervical cancer, such as pathological type, lymph node metastasis and staging. According to the changes, the effect of radiotherapy and chemotherapy can be judged, which can provide a good reference for the diagnosis and treatment of cervical cancer.
7.Impact of repeated sevoflurane anesthesia on hippocampal dendritic spine development in neonatal mice and the mechanism of microtubule polyglutamylation mediated by TTLL6
Yang YU ; Yue ZHAO ; Jingyu FENG ; Yue YANG ; Yanan LI ; Jiafeng YU ; Yonghao YU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(3):193-200
Objective:To evaluate the role of tubulin tyrosin ligase like-6 (TTLL6)-mediated microtubule polyglutamylation and Spastin(a microtubule cleaving protein)-induced excessive microtubule cleavage in the developmental impairment of dendritic spines in neonatal mice following repeated sevoflurane anesthesia, by utilizing TTLL6 conditional knockout mice.Methods:Fifty SPF female TTLL6 brain tissue-specific knockout (TTLL6 CKO: Camk2-Cre + ; TTLL6 f/f) and fifty control (TTLL6 CON: TTLL6 f/f) mice with C57BL/6J background, aged 6 days old were selected.TTLL6 CKO mice were divided into TTLL6 CON control group and TTLL6 CON sevoflurane group, and TTLL6 CKO mice were divided into TTLL6 CKO control group and TTLL6 CKO sevoflurane group, with 25 mice in each group by random block method.Mice in the sevoflurane groups were exposed to 3% sevoflurane with 60% O 2 for 2 hours daily on postnatal days 6, 8, and 10.The mice in control groups received only 60% O 2 under the same condition.The polyGlu-Tubulin and postsynaptic density 95(PSD95) protein expression were detected using Western blot. The expressions of TTLL6, Spastin, and α-Tubulin were assessed via immunofluorescence.Golgi staining and electron microscopy were employed to observe the density of hippocampal dendritic spines and synaptic conditions. The Morris water maze test was used to evaluate spatial memory capabilities. Statistical analysis was performed using GraphPad Prism 8.0 software. Results:(1) Behavioral results showed significant time and group interactions among the four groups in terms of latency to find the platform ( F=8.22, P<0.001).Mice in the TTLL6 CON sevoflurane group had a significantly longer escape latency on days 3-7 compared with the TTLL6 CON control group (all P<0.05), while there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group (all P>0.05). The number of platform crossings differed significantly among the four groups ( H=11.95, P=0.007).The TTLL6 CON sevoflurane group had significantly fewer crossing times than the TTLL6 CON control group ( P<0.05), but no significant difference was observed between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). (2) Golgi staining and electron microscopy results revealed significant differences in dendritic spine density and synapse number among the four groups( F=29.00, 41.94, both P<0.001). The dendritic spine density ((5.83±0.40)/10 μm) and the number of synapses ((3.67±0.58)/10 μm) in the TTLL6 CON sevoflurane group were both significantly lower than those in the TTLL6 CON control group ((12.87±1.70)/10 μm, (9.33±0.57)/10 μm)(both P<0.05). In contrast, there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group (both P>0.05). (3) Immunofluorescence results showed significant differences in the percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the CA3 region of the hippocampus among the four groups of mice ( F=215.20, 26.08, both P<0.001). The percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the TTLL6 CON sevoflurane group ((16.75±1.81) %, (47.98±8.42) %) were significantly higher than those in the TTLL6 CON control group ((2.44±0.58) %, (20.07±4.54) %)(both P<0.05), while there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group ( P>0.05). (4) Western blot results indicated significant differences in the expression of polyGlu-Tubulin and PSD95 proteins in the hippocampal tissue among the four groups of mice ( F=19.66, 8.57, both P<0.001). The TTLL6 CON sevoflurane group had higher polyGlu-Tubulin expression (0.86±0.19) and lower PSD95 expression (0.61±0.13) compared to the TTLL6 CON control group (0.51±0.11, 1.01±0.07) (both P<0.05).However, there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). Conclusion:The mechanism underlying long-term cognitive impairment in developing brain of neonatal mice caused by repeated sevoflurane anesthesia may relate to the upregulation of TTLL6-induced microtubule polyglutamylation and accelerated Spastin-mediated microtubule severing, which ultimately leads to abnormal dendritic spine development.
8.Effects of a matrix metalloproteinase inhibitor on learning and memory function and hippocampal myelin-related proteins in epileptic model rats
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(6):481-487
Objective:To investigate the effects of a matrix metalloproteinase(MMP) inhibitor (ilomastat, GM6001) on learning and memory function and hippocampal myelin-related proteins in epileptic model rats.Methods:Thirty 8-week-old male SPF Sprague-Dawley rats were randomly divided into control group, intervention control group, short-term model group, long-term model group and long-term intervention group, with 6 rats in each group.The lithium-pilocarpine method was used to induce status epilepticus (SE). SE was terminated respectively by intraperitoneal injection of diazepam(10 mg/kg) at 15 min in short-term model group and at 30 min both in the long-term model group and long-term intervention group. Rats in intervention control group and long-term intervention group were treated with GM6001 (20 μg/kg) via tail vein injection. Morris water maze test was used to assess the learning and memory function and the blood-brain barrier permeability was evaluated by Evans blue (EB) staining. The levels of serum MMP, the hippocampal myelin basic protein (MBP) and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were measured by ELISA and Western blot.Statistical analysis was performed by SPSS 21.0 software, with repeated measures ANOVA for Morris water maze data and one-way ANOVA with LSD post hoc test for other comparisons.Results:(1) In the water maze test, the interaction between the time and group on the latencies reached to the platform showed no significance among the 5 groups of rats ( F=0.430, P=0.970). The main effects of time and group on latencies were both significant among the 5 groups( F=144.521, 12.819, both P<0.001).From the second day to the fifth day, the latencies reached to the platform of rats in the long-term model group were significantly higher than those in the control group and in the long-term intervention group (both P<0.05). There were statistically significant differences in the latency of the first time reached the platform, the duration in the target quadrant, the frequency of crossing the platform and the distance to the platform among the 5 groups ( F=7.008, 7.306, 15.704, 11.559, all P<0.05). In the long-term intervention group, the latency of the first time reached the platform ((13.71±4.41) s) and the distance to the platform ((60.37±8.59) cm) were significantly lower than those in the long-term model group ((23.52±5.34) s, (73.06±12.01) cm) (both P<0.05), and the duration in the target quadrant ((10.93±2.99) s) and the frequency of crossing the platform (2.00(1.75, 2.75)times) were significantly higher than those of the long-term model group ((6.04±4.33) s, 1.00(0, 1.00)times) (both P<0.05).(2) The hippocampal EB fluorescence intensity and the serum levels of MMP-2 and MMP-9 were significantly different among the 5 groups ( F=15.249, 7.951, 33.299, all P<0.001). The EB fluorescence intensity of the long-term model group ((0.18±0.03) /100 μm 2) was significantly higher than that in control group ((0.09±0.02) /100 μm 2) and the long-term intervention group ((0.12±0.04) /100 μm 2) (both P<0.05). The serum MMP-2 and MMP-9 levels in the long-term model group ((10.91±1.36) ng/mL, (10.96±1.28) ng/mL) were significantly higher than those of the control group ((7.89±1.04) ng/mL, (4.20±1.48) ng/mL) and the long-term intervention group ((6.49±1.12) ng/mL, (8.06±0.91) ng/mL) (all P<0.05). (3) The expression levels of hippocampal MBP and CNPase were significantly different among the 5 groups ( F=8.757, 4.116, both P<0.05). The expression levels of MBP and CNPase in long-term model group ((1.00±0.19), (0.93±0.21)) were significantly lower than those in the control group ((1.57±0.27), (1.36±0.22)) and the long-term intervention group ((1.45±0.19), (1.23±0.26)) (all P<0.05). Conclusion:The MMP inhibitor GM6001 can ameliorate learning and memory deficits in epileptic model rats, potentially by reducing blood-brain barrier permeability and alleviating hippocampal myelin damage.
9.Identification of a Fetal De Novo Splice Variant in ARCN1 Associated With Growth and Skeletal Abnormalities
Wencong HE ; Zejun YANG ; Jianjian CUI ; Ruilin MA ; Hui TAO ; Yanan LI ; Yin ZHAO
Maternal-Fetal Medicine 2025;07(1):9-14
Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.
10.Multicenter Retrospective Evaluation of the Chinese Expert Consensus Scoring System for the Diagnosis of Obstetrical DIC
Jianjian CUI ; Ziyang LIU ; Wencong HE ; Ruifen SU ; Ruilin MA ; Hui TAO ; Zejun YANG ; Lei SUN ; Shaoqi CHEN ; Yanan LI ; Zhishan JIN ; Yin ZHAO
Maternal-Fetal Medicine 2025;07(4):216-227
Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.

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