Objective:To carry out carrier screening among people of childbearing age, detect the pathogenic genes of monogenic genetic diseases and analyze the carrier status of pathogenic variants, so as to provide fertility guidance and intervention measures for high-risk families.Methods:From August 2022 to August 2023, 1 533 families of childbearing age who met the criteria were recruited in the Chinese PLA General Hospital, including a total of 3 044 subjects. According to the standard enrollment procedure, 223 genes (197 autosomal recessive genes and 26 X-linked genes) of the subjects were tested. According to the screening results, genetic counseling and fertility guidance were provided to the subjects. Invasive prenatal diagnosis was performed for high-risk couples (both couples being carriers of the same autosomal recessive disease gene or the woman was a carrier of X-linked disease gene), and their pregnancy pattern, outcome and offspring phenotype were followed up.Results:(1) A total of 3 044 cases from 1 511 couples and women of childbearing age from 22 families were included for carrier screening. Totally 1 503 families chose simultaneous screening and 30 families chose sequential screening out of the 1 533 families. Among the 3 044 subjects, 1 603 individuals carried at least one pathogenic or likely pathogenic variant, and the overall carrier rate was 52.66% (1 603/3 044). A total of 2 292 pathogenic or likely pathogenic variants were detected, and 0.75 variants (2 292/3 044) were detected per capita. (2) The three genes with the highest carrier rates were GJB2 (8.67%, 264/3 044), CYP21A2 (3.19%, 97/3 044) and PAH (3.09%, 94/3 044). There were 32 genes with a carrier rate ≥1/200, 17 genes with a carrier rate ≥1/100, and 7 genes with a carrier rate ≥1/50. (3) Thirty-eight high-risk families were identified. After excluding G6PD gene mutation, there were 33 high-risk families, of which 25 couples were carriers of the same autosomal recessive gene, 9 women were carriers of X-linked gene, and 1 family was double high-risk couple with both autosomal recessive and X-linked gene. After further excluding the GJB2 c.109G>A mutation, 21 high-risk families were identified. Preimplantation genetic testing for monogenic disease was performed in 12 families after genetic counseling. Prenatal diagnosis was completed in 4 out of 5 high-risk families who conceived naturally. Two fetuses carried the parental variants and terminated the pregnancy, one fetus did not carry the parental variants but was induced due to trisomy 21 syndrome, and one fetus was a carrier of congenital disorders of glycosylation type 1a.Conclusions:Carrier screening effectively identifies high-risk genetic disease families and provides reproductive guidance to prevent the birth of affected children. However, establishing multidisciplinary team is essential for managing complex cases. Implementation should prioritize prenatal institutions with genetic counseling or diagnostic expertise for monogenic disorders or established referral networks.

Objective:To carry out carrier screening among people of childbearing age, detect the pathogenic genes of monogenic genetic diseases and analyze the carrier status of pathogenic variants, so as to provide fertility guidance and intervention measures for high-risk families.Methods:From August 2022 to August 2023, 1 533 families of childbearing age who met the criteria were recruited in the Chinese PLA General Hospital, including a total of 3 044 subjects. According to the standard enrollment procedure, 223 genes (197 autosomal recessive genes and 26 X-linked genes) of the subjects were tested. According to the screening results, genetic counseling and fertility guidance were provided to the subjects. Invasive prenatal diagnosis was performed for high-risk couples (both couples being carriers of the same autosomal recessive disease gene or the woman was a carrier of X-linked disease gene), and their pregnancy pattern, outcome and offspring phenotype were followed up.Results:(1) A total of 3 044 cases from 1 511 couples and women of childbearing age from 22 families were included for carrier screening. Totally 1 503 families chose simultaneous screening and 30 families chose sequential screening out of the 1 533 families. Among the 3 044 subjects, 1 603 individuals carried at least one pathogenic or likely pathogenic variant, and the overall carrier rate was 52.66% (1 603/3 044). A total of 2 292 pathogenic or likely pathogenic variants were detected, and 0.75 variants (2 292/3 044) were detected per capita. (2) The three genes with the highest carrier rates were GJB2 (8.67%, 264/3 044), CYP21A2 (3.19%, 97/3 044) and PAH (3.09%, 94/3 044). There were 32 genes with a carrier rate ≥1/200, 17 genes with a carrier rate ≥1/100, and 7 genes with a carrier rate ≥1/50. (3) Thirty-eight high-risk families were identified. After excluding G6PD gene mutation, there were 33 high-risk families, of which 25 couples were carriers of the same autosomal recessive gene, 9 women were carriers of X-linked gene, and 1 family was double high-risk couple with both autosomal recessive and X-linked gene. After further excluding the GJB2 c.109G>A mutation, 21 high-risk families were identified. Preimplantation genetic testing for monogenic disease was performed in 12 families after genetic counseling. Prenatal diagnosis was completed in 4 out of 5 high-risk families who conceived naturally. Two fetuses carried the parental variants and terminated the pregnancy, one fetus did not carry the parental variants but was induced due to trisomy 21 syndrome, and one fetus was a carrier of congenital disorders of glycosylation type 1a.Conclusions:Carrier screening effectively identifies high-risk genetic disease families and provides reproductive guidance to prevent the birth of affected children. However, establishing multidisciplinary team is essential for managing complex cases. Implementation should prioritize prenatal institutions with genetic counseling or diagnostic expertise for monogenic disorders or established referral networks.

OBJECTIVE To evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.

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 evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.

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.

"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 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.

Objective:To explore the occurrence of adverse reactions of lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19).Methods:The medical records of patients with COVID-19 who received LPV/r treatment in the Fourth People′s Hospital of Nanning from January 24th to February 6th, 2020 were collected and the occurrence of adverse events during the treatment was retrospectively analyzed. According to the 5 principles of adverse drug reaction correlation evaluation proposed in the Handbook of Adverse Drug Reaction Reporting and Monitoring in China, adverse events that were certainly related, probably related, and possibly related to LPV/r were defined as LPV/r-related adverse reactions. The incidence of adverse reactions was calculated and the main clinical manifestations and severity of adverse reactions [grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death); grade 3-5 was defined as severe adverse reaction] were analyzed. Results:A total of 28 patients were enrolled in the analysis, including 13 males and 15 females, aged from 18 to 70 years with an average age of 44 years. The courses of treatment with LPV/r of patients ranged from 2 to 12 days, with a median course of 6 days. Of the 28 patients, 18 developed LPV/r related adverse reactions, with an incidence of 64.3%. The LPV/r-related adverse reactions in 18 patients included gastrointestinal reactions in 14 patients (grade 1 in 13 patients and grade 2 in 1 patient), bradycardia in 2 patients (grade 2 in both patients), and acute hemolysis in 1 patient (grade 3), and liver injury in 1 patient (grade 3), and no grade 4 or 5 adverse reactions occurred. The incidence of severe adverse reactions was 7.1%. Thirteen patients with grade 1 adverse reactions did not affect the treatment, and the symptoms were relieved after 2-7 days of continuous medication. LPV/r was discontinued in 5 patients with grade 2 or 3 adverse reactions, 4 of whom received symptomatic treatment, and the symptoms disappeared 2-10 days later.Conclusions:The incidence of adverse reactions in COVID-19 patients treated with LPV/r in our hospital was 64.3%. LPV/r mainly leads to mild gastrointestinal reactions and can also lead to bradycardia, acute hemolysis, and liver injury. Blood routine, liver function, and electrocardiogram need to be monitored during the treatment.

Objective:To explore the occurrence of adverse reactions of lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19).Methods:The medical records of patients with COVID-19 who received LPV/r treatment in the Fourth People′s Hospital of Nanning from January 24th to February 6th, 2020 were collected and the occurrence of adverse events during the treatment was retrospectively analyzed. According to the 5 principles of adverse drug reaction correlation evaluation proposed in the Handbook of Adverse Drug Reaction Reporting and Monitoring in China, adverse events that were certainly related, probably related, and possibly related to LPV/r were defined as LPV/r-related adverse reactions. The incidence of adverse reactions was calculated and the main clinical manifestations and severity of adverse reactions [grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death); grade 3-5 was defined as severe adverse reaction] were analyzed. Results:A total of 28 patients were enrolled in the analysis, including 13 males and 15 females, aged from 18 to 70 years with an average age of 44 years. The courses of treatment with LPV/r of patients ranged from 2 to 12 days, with a median course of 6 days. Of the 28 patients, 18 developed LPV/r related adverse reactions, with an incidence of 64.3%. The LPV/r-related adverse reactions in 18 patients included gastrointestinal reactions in 14 patients (grade 1 in 13 patients and grade 2 in 1 patient), bradycardia in 2 patients (grade 2 in both patients), and acute hemolysis in 1 patient (grade 3), and liver injury in 1 patient (grade 3), and no grade 4 or 5 adverse reactions occurred. The incidence of severe adverse reactions was 7.1%. Thirteen patients with grade 1 adverse reactions did not affect the treatment, and the symptoms were relieved after 2-7 days of continuous medication. LPV/r was discontinued in 5 patients with grade 2 or 3 adverse reactions, 4 of whom received symptomatic treatment, and the symptoms disappeared 2-10 days later.Conclusions:The incidence of adverse reactions in COVID-19 patients treated with LPV/r in our hospital was 64.3%. LPV/r mainly leads to mild gastrointestinal reactions and can also lead to bradycardia, acute hemolysis, and liver injury. Blood routine, liver function, and electrocardiogram need to be monitored during the treatment.