Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

Objective:To reassess the pathogenicity of copy number variants (CNVs) involving chromosomal microdeletions and microduplications classified as variants of uncertain significance (VUS).Methods:This retrospective study analyzed 1 882 pregnant women who underwent invasive prenatal diagnosis for chromosomal microarray analysis (CMA) at the First Medical Center, Chinese PLA General Hospital between January 1, 2018, and December 31, 2022. The results were classified according to the American College of Medical Genetics and Genomics guidelines, with 82 fetuses rated as VUS selected for the study. We analyzed invasive prenatal diagnostic indications, followed up on fetal ultrasound findings, parental origin identification results, and pregnancy outcomes, and reclassified VUS CNVs based on the latest evidence. Descriptive statistical analysis was applied to the data.Results:(1) Among the 82 fetuses with VUS CNVs, prenatal diagnostic indications included fetal structural abnormalities detected by ultrasound (21 cases, 25.6%), abnormal non-invasive prenatal testing (NIPT) results (12 cases, 14.6%), high-risk serum screening (seven cases, 8.5%), advanced maternal age (≥35 years at expected delivery, 28 cases, 34.1%), and other indications (14 cases, 17.1%). Sixteen cases (19.5%) exhibited abnormal phenotypes, with seven pregnancies terminated due to severe structural abnormalities detected by prenatal ultrasound. Seventy-five live births were followed up for 25 (13-66) months. (2) Among the 82 cases, five fetuses had two VUS CNVs detected by CMA, while the remaining 77 had only one, totaling 87 VUS CNVs. Of these, 63 (72.4%) were chromosomal microduplications and 24 (27.6%) were chromosomal microdeletions. The size of the CNV segments ranged from 0.85 (0.05-5.61) Mb, with 82 segments less than 2 Mb. Parental origin identification was refused by 44 cases (53.7%), while 38 (46.3%) underwent the test, revealing eight (21.0%) de novo variants and 30 (78.9%) inherited from either parent (12 maternal and 18 paternal). (3) Among the 87 VUS CNVs, the ratings of 11 CNVs (12.6%) changed after re-evaluation. This included one 4p16.2 microdeletion and two 15q11.2 microdeletions being upgraded to pathogenic, one 16p13.11 microduplication being upgraded to likely pathogenic, one Xp22.31 microduplication and two 2q13 microdeletions being downgraded to likely benign, and four Xp22.31 microduplications being downgraded to benign. (4) Among the 16 fetuses with abnormal phenotypes, seven with prenatal abnormalities terminated pregnancies, including six with structural abnormalities and one with severe fetal growth restriction. After re-evaluation, one case was upgraded to pathogenic, while six remained VUS. Nine live births with postnatal abnormal phenotypes showed no change in classification after re-evaluation. Among the 66 cases (80.5%) without abnormal phenotypes, 10 had their classifications changed after re-evaluation. Conclusions:Fetuses with VUS CNVs often exhibit no significant abnormal phenotypes and have a relatively favorable prognosis, however, further floow-up is still needed. Parental origin identification can provide valuable insights for genetic counseling.

Objective:To investigate the reasonable airflow organization and exhaust system facilities during the operation of the inspection workshop, and solve the problem of the accumulation of harmful gases such as ozone and nitrogen oxides in the workshop.Methods:In May 2023, computational fluid dynamics (CFD) technology was used to numerically simulate the diffusion of ozone and nitrogen oxides generated by industrial radiographic inspection operations, and the comparative detection method was used to analyze the ozone and nitrogen oxides concentrations before and after the renovation of the ventilation system of the inspection workshop.Results:After the renovation of ventilation system, the average concentration of ozone in the inspection workshop decreased from 0.81 mg/m 3 to 0.03 mg/m 3, and the average concentration of nitrogen oxides decreased from 0.42 mg/m 3 to 0.01 mg/m 3, and the differences were statistically significant ( t=20.51, 10.38, P<0.001) . Conclusion:The ventilation facilities of the inspection workshop are set up in the airflow organization mode of sending up and down the exhaust, and the ventilation pipes are scientifically designed through the calculation of ventilation hydraulic balance, which can effectively control the concentration of harmful gases in the inspection workshop.

Objective To investigate the relationship between coronary artery plaque AI quantitative parameter and FFR-CT in coronary computed tomography angiography.Methods A total of 84 patients suspected of having CAD[52 males and 32 females,aged 27 to 81 years with a mean age of(58.1±11.9)years]were enrolled in this study.All patients underwent coronary computed tomography angiography.The CCTA data was processed using shukun(SK)software for labeling and analysis of the coronary arteries,as well as obtaining quantitative parameters of coronary artery plaque AI and corresponding FFR-CT values.The quantitative parameters included plaque length,total volume,minimum lumen area(MLA),minimal lumen degree(MLD),lipid composition volume and proportion,fibrous-lipid composition volume and proportion,fibrous composition volume and proportion,calcified composition volume and proportion.Coronary artery hemodynamic abnormality or myocardial ischemia was defined as an FFR-CT value≤0.8.Correlational analysis was performed to evaluate the association between AI plaque quantitative param-eters and FFR-CT values.Univariate and multivariate binary logistic regression analyses were conducted to identify independent risk factors for predicting FFR-CT≤0.8.The predictive performance of the model based on AI plaque quantitative parameters was assessed using receiver operating characteristic(ROC)curve analysis and calculation of the area under the curve(AUC).Sensitivities,specificities,diagnostic test accuracy rates were also calculated.Results The predominant symptoms observed in the cohort of 84 patients were chest pain(n=39,46.4%)and distress(n=27,32.1%).Spearman analysis results revealed a weak positive correlation between FFR-CT and MLA(r=0.49,P<0.0001),while weak negative correlations were found for plaque length,total volume,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume(r=-0.44,-0.56,-0.40,-0.36,-0.42,-0.40;all P<0.05).Additionally,MLD exhibited a moderate negative correlation with FFR-CT(r=-0.60,P<0.0001).In the univariate binary logistic regression analysis,several variables including plaque length,total volume,MLA,MLD,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume were found to be independently associated with FFR-CT≤0.8(All P<0.05).The adjusted multivariate binary logistic regression analysis model revealed that MLD was the sole independent predictor(OR=1.082,95%CI:1.034～1.133,P=0.001).The logistics re-gression model expression was logit(P)=0.079X1-4.052,where X1 represents the value of MLD and achieved a predictive accuracy of 85.2%.The ROC AUC of plaque length,total volume,MLA,MLD,lipid composition vol-ume,fibrous-lipid composition volume,fibrous composition volume and calcified composition volume were 0.796,0.886,0.711,0.754 and 0.698 respectively,and the coresponding sensitivities and specificities were 47.83%,73.91%,73.90%,52.17%,60.87%and 92.11%,73.68%,60.53%,84.21%,89.47%.The five in-dexes combined diagnostic model possessed the largest AUC of 0.906,and 73.91%,71.05%of sensitivity and specificity.Conclusion The AI quantitative parameters of coronary artery plaque exhibited varying degrees of correlation with FFR-CT,while MLD emerged as the sole independent predictor of FFR-CT≤0.8,demonstrating high diagnostic efficiency.

"Chinese model" of organ donation and transplantation in China has won acclaims from all over the world. Current contradictions between unbalanced and inadequate development of organ donation and transplantation and surging public demands for transplant services remain serious. And an acute shortage of donated organs is still the greatest difficulty. Improving organ donation rate per million population (PMP) and organ utilization rate has been a great challenge for organ donation teams in China. This review summarized the relevant experiences of Second Affiliated Hospital of Guangxi Medical University in fostering organ donation culture atmosphere and connotation to accelerate the high-quality development of organ donation. It was intended to provide references for disciplined construction of other organ donation management teams and promote the development of organ donation and transplantation in China.

Objective:To investigate the reasonable airflow organization and exhaust system facilities during the operation of the inspection workshop, and solve the problem of the accumulation of harmful gases such as ozone and nitrogen oxides in the workshop.Methods:In May 2023, computational fluid dynamics (CFD) technology was used to numerically simulate the diffusion of ozone and nitrogen oxides generated by industrial radiographic inspection operations, and the comparative detection method was used to analyze the ozone and nitrogen oxides concentrations before and after the renovation of the ventilation system of the inspection workshop.Results:After the renovation of ventilation system, the average concentration of ozone in the inspection workshop decreased from 0.81 mg/m 3 to 0.03 mg/m 3, and the average concentration of nitrogen oxides decreased from 0.42 mg/m 3 to 0.01 mg/m 3, and the differences were statistically significant ( t=20.51, 10.38, P<0.001) . Conclusion:The ventilation facilities of the inspection workshop are set up in the airflow organization mode of sending up and down the exhaust, and the ventilation pipes are scientifically designed through the calculation of ventilation hydraulic balance, which can effectively control the concentration of harmful gases in the inspection workshop.

Objective:To study the clinical manifestations, diagnostic methods and therapeutic outcomes of transverse testicular ectopia (TTE).Methods:Clinical data of 8 cases of TTE treated in the Department of the First Urologic Surgery, Xinxiang Central Hospital and Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from May 2004 to November 2018 were retrospectively analyzed.Clinical manifestations, diagnostic methods, surgical treatment and follow-up results of TTE were summarized.Results:The age of 8 cases of TTE was 1 year 5 months to 5 years.Among the 8 cases of TTE, 6 cases were involved with the left side and 2 cases with the right side.All patients were admitted due to scrotal emptiness.Three cases were combined with persistent Müllerian duct syndrome (PMDS) and 1 case combined with hypospadias.Preoperative diagnosis of TTE was definitely made in 5 cases, involving 4 cases diagnosed by ultrasound and 1 case diagnosed by magnetic resonance imaging.Laparoscopy was performed in 2 cases, including 1 case treated with laparoscopic scrotopexy, and the other one transferred to an open surgery of trans-septal orchiopexy due to poor development of the spermatic cord.Open surgery was performed in 6 cases, including 1 case with bilateral testicular fixation in the ipsilateral scrotum due to adhesion of spermatic cord closely, and 5 cases with trans-septal orchiopexy.Müllerian ducts residues were excised during surgery in 3 cases combined with PMDS.Postoperative wound infection or hematoma was not reported in all cases.Orchiepididymitis and the involvement of contralateral testes occurred in 1 case treated with trans-septal orchiopexy at 11 months postoperatively, which were relieved after anti-inflammatory treatment.All cases were postoperatively followed up for 3-48 months, and the development and blood supply of bilateral testes were detected normal by ultrasonography.Postoperative testicular atrophy was not reported.Conclusions:The possibility of TTE should be considered in patients with unilateral cryptorchidism combined with contralateral inguinal mass.Ultrasonography is preferred to the diagnosis of TTE.Laparoscopic surgery plays an important role in the diagnosis and treatment of TTE, which is helpful to identify abnormalities in the Müllerian duct structure.

Objective:To explore the efficacy and influencing factors of irinotecan-loaded CalliSpheres drug-eluting bead-transcatheter arterial chemoembolization (DEBIRI-TACE) combined with regorafenib in the third-line or above treatment of unresectable colorectal cancer liver metastases.Methods:From June 2018 to June 2020, 53 patients with unresectable colorectal cancer liver metastases admitted to Linyi Cancer Hospital of Shandong Province who had failed at least second-line systemic chemotherapy were retrospectively analyzed. The patients were divided into observation group (24 cases) and control group (29 cases) according to different treatment regimes. The control group only received regorafenib monotherapy, and the observation group received regorafenib combined with DEBIRI-TACE. According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate (ORR) and disease control rate (DCR) were evaluated, and the progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. The Cox proportional hazards model was used to analyze the OS influencing factors in the observation group. The treatment related adverse reactions were observed.Results:After 2 months of treatment, the ORR of the observation group was 75.0% (18/24) , and the DCR was 91.7% (22/24) , both were higher than those of the control group [6.9% (2/29) and 51.7% (15/29) respectively], with statistically significant differences ( χ2=25.92, P<0.001; χ2=9.94, P=0.002) . There were no statistically significant differences in the incidences of regorafenib-related adverse reactions such as hand-foot skin reaction [62.5% (15/24) vs. 65.5% (19/29) , χ2=0.05, P=0.819], fatigue [41.7% (10/24) vs. 44.8% (13/29) , χ2=0.05, P=0.817], hypertension [29.2% (7/24) vs. 34.5% (10/29) , χ2=0.17, P=0.679], diarrhea [25.0% (6/24) vs. 27.6% (8/29) , χ2=0.04, P=0.832], hoarseness [16.7% (4/24) vs. 17.2% (5/29) , χ2=0.01, P=0.956] and proteinuria [8.3% (2/24) vs. 10.3% (3/29) , χ2=0.06, P=0.803] between the two groups. The main adverse reactions related to DEBIRI-TACE in the observation group were fever, pain, nausea and vomiting, etc., which were relieved after symptomatic treatment. No serious complications such as ectopic embolism of CalliSpheres drug eluting bead occurred. By the end of the follow-up, among the 24 patients in the observation group, the median OS of patients with simultaneous liver metastases was 12 months, and that of patients with metachronous liver metastases was 22 months, with a statistically significant difference ( χ2=4.29, P=0.026) . The median OS of patients with 3-5 liver metastases was 21 months, and that of patients with more than 5 liver metastases was 14 months, with a statistically significant difference ( χ2=3.35, P=0.040) . The median OS of Child-Pugh grade A patients was 22 months, and that of Child-Pugh grade B patients was 13 months, with a statistically significant difference ( χ2=4.22, P=0.027) . The median OS was 16 months in patients with extrahepatic metastases and 23 months in patients without extrahepatic metastases, with a statistically significant difference ( χ2=7.68, P=0.013) . Cox proportional hazards model analysis showed that simultaneous liver metastases ( HR=1.59, 95% CI: 1.02-2.47, P=0.031) and extrahepatic metastases ( HR=1.61, 95% CI: 1.29-2.01, P=0.020) were independent risk factors influencing OS of patients in the observation group. The median PFS of the observation group was 9 months, and that of the control group was 5 months, with a statistically significant difference ( χ2=7.78, P=0.005) . The median OS of the observation group was 17 months, and that of the control group was 11 months, with a statistically significant difference ( χ2=16.81, P<0.001) . Conclusion:DEBIRI-TACE combined with regorafenib is effective in the third-line or above treatment of unresectable colorectal cancer liver metastases, with tolerable adverse reactions. It is a safe and feasible treatment method. The prognosis of patients with simultaneous liver metastases or extrahepatic metastases is worse.

Objective:To analyze the indications for invasive prenatal diagnosis in the third trimester and summarize the pregnant outcome.Methods:Clinical data of 121 women who underwent invasive prenatal diagnosis in the third trimester in the prenatal diagnostic center of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020 was retrospectively analyzed. Different genetic diagnostic methods were used according to different indications. Indications and results of prenatal diagnosis, as well as the complications within two weeks after the invasive procedure, pregnancy outcome, and neonatal follow-up of all the participants were described.Results:Among the 121 cases, 107 cases underwent amniocentesis, seven underwent percutaneous umbilical blood sampling, and seven had both procedures performed at the same time (one underwent thoracocentesis at the same time). Newly identified ultrasound abnormalities in the second and third trimesters were the main indications for prenatal diagnosis, accounting for 99.2%(120/121), of which short limbs and fetal growth restriction accounted for 25.0% (30/120) and 20.0% (24/120), respectively. Genetic abnormalities and congenital diseases were detected in 20 cases with a detection rate of 16.5%(20/121). Among them, there were nine cases of achondroplasia, five cases of pathogenic copy number variations, one case of achondroplasia with pathogenic copy number variation, one trisomy 18, one 47,XXX, one tetrasome mosaicism of 12p, one de novo WTX c. 1072(Exon2) C>Tp.R358X heterozygous mutation, and one fetal hypoproteinemia. In addition, six cases with copy number variation of unknown significance (VUS) were detected, noting for a detection rate of 5.0%(6/121). Among the 20 cases with abnormal detection, 15 were terminated, two delivered prematurely before obtaining the prenatal diagnosis results, one underwent cesarean section before obtaining prenatal diagnostic results and two continued the pregnancies. In the six cases with VUS, one was terminated and the other five continued the pregnancy. Only one case had preterm premature rupture of membranes 2 d after amniocentesis and the incidence rate of complications after all kinds of invasive procedures was 0.8% (1/121). During the neonatal follow-up, postnatal whole exome sequencing revealed monogenetic disorder in two cases with normal prenatal diagnostic results; the patient with 12p chimerism had developmental delay; the one with WTX mutation deceased on the day of born; the rest newborns developed normally. Conclusions:As a relatively safe method, invasive prenatal diagnosis in the third trimester is of great importance and value in reducing the miss diagnostic rate of fetuses with severe genetic diseases and birth defects. The appropriate application of prenatal whole exome sequencing could further help to decrease the miss diagnostic rate of monogenetic disorder.

Objecfive:To investigate the clinical characteristics and surgical management of tumor invasion on recurrent laryngeal nerve at the entrance of larynx in thyroid cancer.Methods:The clinical data of 30 patients with recurrent laryngeal nerve invasion by thyroid cancer from Aug 2012 to Aug 2018 in Cangzhou Central Hospital were analyzed retrospectively. Patients were divided into groups A (14 cases ,nerve was invaded at the larynx) and group B (16 cases,nerve was involved in other parts).Results:Between the two groups, operation time, intraoperative blood loss, number of tumor focus, adhesion and infiltration were not statistically different ( P>0.05). The tumor size in group A was smaller ( t=-3.614, P=0.001), the lymph node metastasis rate was lower ( χ2=5.593, P=0.018), and the microcancer rate was higher ( χ2=4.051, P=0.044).Follow up data up to 24 months showed there were no significant difference in postoperative hoarseness , laryngoscope abnormality and recurrence rate between the two groups (all P>0.05). Conclusion:Patients of thyroid cancer with recurrent laryngeal nerve invasion at the larynx had relatively small tumor size, higher proportion of microcancer, lower rate of lymph node metastasiss.