[Clinicopathological and genetic characteristics of common lymphatic malformations in superficial soft tissues].

Objective: To investigate the clinicopathological features, classification, and genetic characteristics of common lymphatic malformation (CLM) in superficial soft tissue. Methods: A retrospective study of 110 patients with the diagnosis of CLM at the Henan Province People's Hospital, China from August 2019 to August 2022 was performed. The clinicopathological features, relevant immunohistochemical (IHC) staining results, and fluorescence quantitative PCR of PIK3CA mutation were analyzed, and patients were followed up. Results: Among the 110 CLM patients, there were 53 males and 57 females; 65 cases (65/110, 59.1%) were first detected when the patients were≤2 years old. The most common location was the head and neck in 41 cases (41/110, 37.3%). Clinically, 102 cases (102/110, 92.7%) were solitary, 83 cases (83/110, 75.5%) were skin-colored, 69 cases (69/110, 62.7%) had indistinct borders, and 10 cases (10/110, 9.1%) had diffuse and severe macroscopic manifestations. There were 52 macrocystic type (52/110, 47.3%), 23 microcystic type (23/110, 20.9%), and 35 combined type (35/110, 31.8%). The macrocystic CLM presented as soft, translucent masses with large cystic cavities on the cut surface, and histologically they were composed of large, irregularly dilated channels that were thicker with irregular smooth muscle and lymphocytic infiltration. Microcystic CLM showed wartlike projections or translucent blisters on the skin, with small honeycomb structures on the cut surface, and histologically consisted of round or angular dilated small lymphatic vessels with little or no smooth muscle. The combined CLM had both macrocystic and microcystic morphologies. IHC staining showed that the lymphatic endothelial cells were positive for LYVE-1, D2-40, PROX1, CD31, and VEGFR3 but negative for CD34; in the macrocystic and combined CLM vessel walls were positive for SMA. Eight of 13 CLM had PIK3CA mutation. All patients were followed up, and 24 (24/110, 21.8%) had relapses, which more frequently occurred in combined type, followed by microcystic type. Conclusions: CLM is a congenital vascular malformation composed of dilated, abnormal lymphatic channels, with PIK3CA mutation. There are significant differences in clinicopathological characteristics among the different types. Since microcystic and combined CLM are prone to recurrence, accurate pathological subtyping is necessary to guide treatment and to predict prognosis.

[Glomuvenous malformation: a clinicopathological analysis of 31 cases].

Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.

[Prenatal genetic diagnosis of the fetuses with isolated corpus callosum abnormality].

Objective: To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus. Methods: Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children's Medical Center and Qingyuan People's Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal. Results: Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses. Conclusions: Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

The Role of Mitochondrial KATP Channels in the Infarct-Reducing Effect of Normobaric Hypoxia.

We studied the role of KATP channels in the infarct-limiting effect of short-term normobaric hypoxia. Male Wistar rats were subjected to a 45-min coronary artery occlusion followed by a 120-min reperfusion. Normobaric hypoxia was simulated 30 min before coronary artery occlusion: 6 sessions of hypoxia (8% O2, 10 min) and reoxygenation (21% O2, 10 min). The following drugs were administered to rats: glibenclamide, 5-hydroxydecanoate, and HMR1098. It was found that normobaric hypoxia contributes to a decrease in myocardial infarct size by 36%. Preliminary administration of glibenclamide or 5-hydroxydecanoate eliminated the infarct-reducing effect of normobaric hypoxia. Activator of mitochondrial KATP channel diazoxide limited the infarct size. These findings suggest that mitochondrial KATP channels are involved into the cardioprotective effect of normobaric hypoxia.

[The influence of cachexia on the immunotherapy efficacy of Sintilimab for non-small cell lung cancer].

Objective: To investigate whether cachexia affects the treatment effect of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC). Methods: The prognosis of 62 patients with advanced NSCLC who received anti-programmed cell death-1 (PD-1) in Henan Provincial People's Hospital from 2019 to 2021 were retrospectively analyzed. The cachexia was evaluated before and after the second course of immunotherapy. Kaplan-Meier and Log rank methods were used for survival analysis, Cox regression model was used for multivariate analysis, and Spearman's correlation analysis was used for correlation analysis. Results: After the second course of immunotherapy, psoas major muscle area (PMMA) values of the cachexia group and the control group were (14.10±4.09) and (11.66±3.22) cm(2) respectively, with statistics significance (P=0.001). The level of Prealbumin and body weight were correlated with cachexia (P<0.05). The 6-month and 1-year survival rates of 62 cases in the whole group were 58.6% and 42.5%, respectively. The progression-free survival (PFS) in the control group (7.6 months) was higher than that in the cachexia group (3.8 months, P=0.006). The PFS in patients with high expression of PD-L1 (7.1 months) was longer than that of patients with low expression (3.8 months, P=0.009). The overall survival (OS) in the cachexia group (6.3 months) was lower than that in the control group (18.2 months, P=0.006). The OS in patients with high expression of PD-L1 (14.5 months) was longer than that of patients with low expression (1 months, P=0.038). The level of Prealbumin, the level of PD-L1 expression and the change rate of PMMA were related to the OS of the patients (P<0.05). The level of Prealbumin and the change rate of PMMA were the independent influencing factors of the OS (P<0.05). The PMMA and the level of Prealbumin were negatively correlated (r=-0.003 8, P<0.05). Conclusion: Cachexia has a negative impact on the outcomes of patients who received anti-PD-1 immune checkpoint inhibitor therapy.

[Technology specification of bedside hypertonic saline-contrast electrical impedance tomography of lung perfusion and clinical application].

Bedside hypertonic saline-contrast electrical impedance tomography (EIT) method for lung perfusion evaluation has several advantages of bedside, simple, noninvasive and radiation-free. For a long time, EIT perfusion image of hypertonic saline was mostly limited to animal experiments, and related clinical research is in the ascendant. This technical specification for clinical application is reached based on our previous researches, review of literatures in this field. The purpose of this technical specification is to facilitate the unified and standardized use of hypertonic saline-contrast EIT technology for regional lung perfusion, to evaluate the safety and quality control of the technology, and to unify the results.

[Analysis of families with fetal congenital abnormalities but negative prenatal diagnosis by whole exome sequencing].

Objective: To evaluate the value of whole exome sequencing (WES) in prenatal clinical application. Methods: A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed. Results: Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results. Conclusions: WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

Olfactory ensheathing cells improve the survival of porcine neural xenografts in a Parkinsonian rat model.

BACKGROUND: Parkinson's disease (PD) features the motor control deficits resulting from irreversible, progressive degeneration of dopaminergic (DA) neurons of the nigrostriatal pathway. Although intracerebral transplantation of human fetal ventral mesencephalon (hfVM) has been proven effective at reviving DA function in the PD patients, this treatment is clinically limited by availability of hfVM and the related ethical issues. Homologous tissues to hfVM, such as porcine fetal ventral mesencephalon (pfVM) thus present a strong clinical potential if immune response following xenotransplantation could be tamed. Olfactory ensheathing cells (OECs) are glial cells showing immunomodulatory properties. It is unclear but intriuging whether these properties can be applied to reducing immune response following neural xenotransplantation of PD. METHODS: To determine whether OECs may benefit neural xenografts for PD, different compositions of grafting cells were transplanted into striatum of the PD model rats. We used apomorphine-induced rotational behavior to evaluate effectiveness of the neural grafts on reviving DA function. Immunohistochemistry was applied to investigate the effect of OECs on the survival of neuroxenografts and underlying mechanisms of this effect. RESULTS: Four weeks following the xenotransplantation, we found that the PD rats receiving pfVM + OECs co-graft exhibited a better improvement in apomorphine-induced rotational behavior compared with those receiving only pfVM cells. This result can be explained by higher survival of DA neurons (tyrosine hydroxylase immunoreactivity) in grafted striatum of pfVM + OECs group. Furthermore, pfVM + OECs group has less immune response (CD3+ T cells and OX-6+ microglia) around the grafted area compared with pfVM only group. These results suggest that OECs may enhance the survival of the striatal xenografts via dampening the immune response at the grafted sites. CONCLUSIONS: Using allogeneic OECs as a co-graft material for xenogeneic neural grafts could be a feasible therapeutic strategy to enhance results and applicability of the cell replacement therapy for PD.

Regulation of Noise-Induced Loss of Serotonin Transporters with Resveratrol in a Rat Model Using 4-[18F]-ADAM/Small-Animal Positron Emission Tomography.

Serotonin (5-HT) plays a crucial role in modulating the afferent fiber discharge rate in the inferior colliculus, auditory cortex, and other nuclei of the ascending auditory system. Resveratrol, a natural polyphenol phytoalexin, can inhibit serotonin transporters (SERT) to increase synaptic 5-HT levels. In this study, we investigated the effects of resveratrol on noise-induced damage in the serotonergic system. Male Sprague-Dawley rats were anaesthetized and exposed to an 8-kHz tone at 116 dB for 3.5 h. Resveratrol (30 mg/kg, intraperitoneal injection [IP]) and citalopram (20 mg/kg, IP), a specific SERT inhibitor used as a positive control, were administered once a day for four consecutive days, with the first treatment occurring 2 days before noise exposure. Auditory brainstem response testing and positron emission tomography (PET) with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM, a specific radioligand for SERT) were used to evaluate functionality of the auditory system and integrity of the serotonergic system, respectively, before and after noise exposure. Finally, immunohistochemistry was performed 1 day after the last PET scan. Our results indicate that noise-induced serotonergic fiber loss occurred in multiple brain regions including the midbrain, thalamus, hypothalamus, striatum, auditory cortex, and frontal cortex. This noise-induced damage to the serotonergic system was ameliorated in response to treatment with resveratrol and citalopram. However, noise exposure increased the hearing threshold in the rats regardless of drug treatment status. We conclude that resveratrol has protective effects against noise-induced loss of SERT.

[Value of intravoxel incoherent motion diffusion weighted imaging in evaluating the microstructure changes in white matter hyperintensities].

Objective: To investigate the value of intravoxel incoherent motion diffusion weighted imaging (IVIM DWI) in evaluating microstructure changes in elderly white matter hyperintensities (WMH) patients and to analyze the correlation between IVIM parameters and severity grading and cognitive scores. Methods: Sixty-two WMH patients in Zhejiang Hospital were collected from December 2014 to March 2018 and underwent conventional magnetic resonance (MR) plain scan and diffusion weighted imaging with different b values. The age was 60-92(74±10) years with 37 males, 25 females. The severity of WMH was assessed by T(2) fluid attenuated inversion recovery (FLAIR) sequence and Fazekas score,which were divided into two subgroups. Slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) from IVIM parameters of double exponential model were compared between regions of WMH (deep WMH (DWMH) and periventricular WMH (PWMH)) and surrounding normal white matter (NWM).The Shapiro-Wilk test was used for normality tests, Kruskal-Wallis tests and Dwass-Steel-Critchlow-Fligner (DSCF) procedure were used for the comparison among these parameters. Furthermore, Wilcoxon two-sample test was used for the comparisons between different severity. Pearson correlation analysis was performed to determine whether these D, D(*), f values were correlated with the mini mental state examination (MMSE) scores. Results: D(D)WMH (0.83(0.72,0.99)×10(-3) mm(2)/s), D(PWMH)((1.13±0.25)×10(-3) mm(2)/s) were significantly higher than D(NWM) ((0.71±0.05)×10(-3) mm(2)/s)(P<0.01). f (DWMH) ((8.94%(7.46%,11.67%)), f (PWMH)(8.34%(6.73%,9.96%)) were significantly higher than f (NWM)(6.71%±1.72%)(P<0.01).D in DWMH were significantly lower than that in PWMH(P<0.01), there's no statistically difference between other groups. D in severe WMH (both DWMH and PWMH) were significantly higher than that in mild WMH (P=0.000 1, P=0.04). Only f in PWMH were positively associated with the MMSE scores (r=0.326 5,P<0.05). Conclusions: IVIM DWI can noninvasively assess the variation of microstructure diffusion and perfusion in WMH in one sequence,which may objectively reflect the severity of these lesions. This method has important clinical significance for better assessment and management of this disease.

Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities.

OBJECTIVES: To evaluate the diagnostic yield of prenatal whole exome sequencing (WES) for monogenic disorders in fetuses with structural malformations and normal results on cytogenetic testing, and to describe information on pathogenic variants that is provided by WES. METHODS: Karyotyping, chromosomal microarray analysis (CMA) and WES were performed sequentially on stored samples from a cohort of 3949 pregnancies with fetal structural abnormalities detected on ultrasound and/or magnetic resonance imaging, referred between January 2011 and December 2015. Diagnostic rates of the three techniques were investigated overall, for phenotypic subgroups and for proband-only vs fetus-mother-father samples. Information on pathogenic variants was identified by WES. RESULTS: Overall, 18.2% (720/3949) of fetuses had an abnormal karyotype. Pathogenic copy number variants were detected on CMA in 8.2% (138/1680) of fetuses that had a normal karyotype result. WES performed on a subgroup of 196 fetuses with normal CMA and karyotype results revealed the putative genetic variants responsible for the abnormal phenotypes in 47 cases (24%). The molecular diagnosis rates for fetus-mother-father and proband-only samples were 26.5% (13/49) and 23.1% (34/147), respectively. Variants of uncertain significance were detected in 12.8% (25/196) of fetuses, of which 22 were identified in the fetal proband-only group (15%; 22/147) and three in the fetus-mother-father group (6.1%; 3/49). The incidental finding rate was 6.1% (12/196). CONCLUSIONS: WES is a promising method for the identification of genetic variants that cause structural abnormalities in fetuses with normal results on karyotyping and CMA. This enhanced diagnostic yield has the potential to improve the clinical management of pregnancies and to inform better the reproductive decisions of affected families. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Anatomic double bundle ACL reconstruction outperforms any types of single bundle ACL reconstructions in controlling dynamic rotational laxity.

PURPOSE: To compare the different types of ACL reconstructions in terms of knee dynamic laxity evaluated by acceleration. METHODS: Sixteen fresh frozen cadaveric knees were used. Pivot shift test was manually performed while monitoring the tibial acceleration by use of a triaxial accelerometer. The test was repeated before and after the ACL resection and reconstruction. Three types of ACL reconstruction were tested: (1) Anatomic Single-Bundle reconstruction (n = 8), the graft was placed at the center of the ACL footprint for the both femoral and tibial sides (tunnel diameter: 8mm); (2) Conventional Single-Bundle reconstruction (n = 8), the graft was placed from the tibial PL footprint to femoral high AM position (tunnel diameter: 8mm) and (3) Anatomic Double-Bundle reconstruction (n = 8). The acceleration in each of three x-y-z directions and the overall magnitude of acceleration was calculated to evaluate dynamic rotational laxity and compared between different ACL reconstructions. RESULTS: The overall magnitude of acceleration was significantly different between ACL intact and deficient knees (p < 0.0001). The acceleration was reduced by the DB ACL reconstruction to the intact level (n.s.), but the two SB ACL reconstruction failed to achieve the intact level of the acceleration (p = 0.0002non-anatomic SB, p < 0.0001 anatomic SB). CONCLUSION: The anatomic DB reconstruction better restores dynamic rotational laxity when compared to the SB ACL reconstructions no matter if the tunnel placement was anatomic. The anatomic DB reconstruction better restores dynamic rotational laxity when compared to both anatomic and non-anatomic SB ACL reconstruction. For this reason anatomic DB ACL reconstruction is recommended for cases where rotational laxity is an issue.

Nonsensory target-dependent organization of piriform cortex.

The piriform cortex (PCX) is the largest component of the olfactory cortex and is hypothesized to be the locus of odor object formation. The distributed odorant representation found in PCX contrasts sharply with the topographical representation seen in other primary sensory cortices, making it difficult to test this view. Recent work in PCX has focused on functional characteristics of these distributed afferent and association fiber systems. However, information regarding the efferent projections of PCX and how those may be involved in odor representation and object recognition has been largely ignored. To investigate this aspect of PCX, we have used the efferent pathway from mouse PCX to the orbitofrontal cortex (OFC). Using double fluorescent retrograde tracing, we identified the output neurons (OPNs) of the PCX that project to two subdivisions of the OFC, the agranular insula and the lateral orbitofrontal cortex (AI-OPNs and LO-OPNs, respectively). We found that both AI-OPNs and LO-OPNs showed a distinct spatial topography within the PCX and fewer than 10% projected to both the AI and the LO as judged by double-labeling. These data revealed that the efferent component of the PCX may be topographically organized. Further, these data suggest a model for functional organization of the PCX in which the OPNs are grouped into parallel output circuits that provide olfactory information to different higher centers. The distributed afferent input from the olfactory bulb and the local PCX association circuits would then ensure a complete olfactory representation, pattern recognition capability, and neuroplasticity in each efferent circuit.

Genotype distribution characteristics of high-risk human papillomaviruses in women from Shanghai, China.

High-risk human papillomaviruses (HPVs) are highly prevalent worldwide, and HPV genotype distribution varies regionally. Molecular surveys of HPVs are important for effective HPV control and prevention. Fifteen high-risk HPV strains (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and six low-risk HPV strains (HPV6, 11, 42, 43, 44, CP8304) were detected by cervical cytology from 10 501 subjects. High-risk HPVs, low-risk HPVs, and both high- and low-risk HPVs were detected in 14·5%, 2·8%, and 2·4% of cases, respectively. Of 1782 subjects with high-risk HPV infection, 75·5%, 18·1%, and 6·4% were infected with one, two, and ⩾3 strains of high-risk HPVs, respectively. HPV52, HPV16, and HPV58 were the top three most dominant high-risk HPV genotypes in our population with positivity rates of 23·0%, 17·7% and 16·9%, respectively. Multiple infection was common, with significantly higher co-infection rates of HPV58/HPV33 (12·9%) and HPV58/HPV52 (11·3%). Further data comparisons showed that HPV genotype distribution varied markedly between domestic and international regions. In conclusion, a monolithic vaccination strategy is obviously impractical, and regional HPV surveillance is essential to optimize current HPV control and prevention.

Detection of fetal copy number variants by non-invasive prenatal testing for common aneuploidies.

OBJECTIVE: To evaluate the clinical performance of non-invasive prenatal testing (NIPT) in detecting fetal copy number variants (CNVs). METHODS: NIPT of cell-free fetal DNA was performed retrospectively, using stored maternal plasma, at an average gestational age of 21.1 weeks in 117 pregnant women who had previously undergone invasive prenatal testing for chromosome microarray analysis (CMA). Among the fetal samples tested by CMA, 18 had positive results (CNVs > 1 megabase (Mb)) and 99 had negative results (CNVs < 1 Mb or without CNVs detected). The results of NIPT and CMA were then compared. RESULTS: In the 11 CMA-positive samples with CNVs > 5 Mb, the detection rate of CNVs was 90.9%; the one case missed by NIPT had a fetal fraction of 4.7%. For the other seven CMA-positive samples with CNVs < 5 Mb, the detection rate was 14.3%; only one case with a 2.82-Mb duplication was detected, with a fetal fraction of 26.7%. For 35.7% (5/14) of CNVs detected by both NIPT and CMA, the differences in fragment length were within ± 1 Mb. In this study, the overall sensitivity and specificity of NIPT for detecting CNVs > 1 Mb were 61.1% and 95.0%, respectively, with a false-positive rate of 5.0%. CONCLUSIONS: Our results demonstrate that NIPT for common aneuploidies can detect fetal CNVs > 5 Mb with high sensitivity, provided that fetal fraction is high enough, without increasing sequencing depth. The detection power of NIPT is determined mostly by fetal fraction and CNV size. A positive NIPT screening result for CNVs must be interpreted with caution and validated by additional diagnostic study.