Objective:To detect the cystic fibrosis transmembrane transduction regulator(CFTR)gene mutations and congenital bilateral absence of vas deferens(CBAVD)susceptibility gene mutations in pa-tients with CBAVD,and to explore their association with the risk of CBAVD.Methods:Whole-exome sequencing and Sanger sequencing validation were conducted on the pathogenic genes CFTR,adhesion G protein-coupled receptor G2(ADGRG2),sodium channel epithelial 1 subunit beta(SCNN1B),carbonic anhydrase 12(CA12),and solute carrier family 9 member A3(SLC9A3)in thirteen cases of isolated CBAVD patients.The polymorphic loci,intron and flanking sequences of CFTR gene were amplified by polymerase chain reaction(PCR)followed by Sanger sequencing.Bioinformatics methods were employed for conservative analysis and deleterious prediction of novel susceptibility gene mutations in CBAVD.Ge-netic analysis was performed on the pedigree of one out of thirteen patients with CBAVD to evaluate the risk of inheritance in offspring.Results:Exome sequencing revealed CFTR gene exon mutations in only six of the thirteen CBAVD patients,with six missense mutations c.2684G＞A(p.Ser895Asn),c.4056G＞C(p.Gln1352His),c.2812G＞(p.Val938Leu),c.3068T＞G(p.Ile1023Arg),c.374T＞C(p.Ile125Thr),c.1666A＞G(p.Ile556Val)),and one nonsense mutation(c.1657C＞T(p.Arg553Ter).Among these six patients,two also had the CFTR homozygous p.V470 site,additional-ly,mutations in CFTR gene exon regions were not detected in the remaining seven patients.Within the thirteen CBAVD patients,three carried the homozygous p.V470 polymorphic site,four carried the 5T al-lele,two carried the TG13 allele,and ten carried the c.-966T＞G site.Four CBAVD patients simulta-neously carried 2-3 of the aforementioned CFTR gene mutation sites.Susceptibility gene mutations in CBAVD among the thirteen patients included one ADGRG2 missense mutation c.2312A＞G(p.Asn771Ser),two SLC9A3 missense mutations c.2395T＞C(p.Cys799Arg),c.493G＞A(p.Val165Ile),one SCNN1B missense mutation c.1514G＞A(p.Arg505His),and one CA12 missense mutation c.1061C＞T(p.Ala354Val).Notably,the SLC9A3 gene c.493 G＞A(p.Val165Ile)mutation site was first identi-fied in CBAVD patients.The five mutations exhibited an extremely low population mutation frequency in the gnomAD database,classifying them as rare mutations.Predictions from Mutation Taster and Poly-phen-2 software indicated that the harmfulness level of the SLC9A3 gene c.493G＞A(p.Val165Ile)site and the SCNN1B gene c.1514G＞A(p.Arg505His)site were disease causing and probably damaging.The genetic analysis of one pedigree revealed that the c.1657C＞T(p.Arg553Ter)mutation in the proband was a de novo mutation,as neither the proband's father nor mother carried this mutation.The proband and his spouse conceived a daughter through assisted reproductive technology,and the daughter inherited the proband's pathogenic mutation c.1657C＞T(p.Arg553Ter).Conclusion:CFTR gene mutations remain the leading cause of CBAVD in Chinese patients;however,the distribution and fre-quency of mutations differ from data reported in other domestic and international studies,highlighting the need to expand the CFTR mutation spectrum in Chinese CBAVD patients.The susceptibility genes ADGRG2,SLC9A3,SCNN1B,and CA12 may explain some cases of CBAVD without CFTR mutations.Given the lack of specific clinical manifestations in CBAVD patients,it is recommended that clinicians conduct further physical examinations and consider scrotal or transrectal ultrasound before making a defi-nitive diagnosis.It is advisable to employ CFTR gene mutation testing in preconception genetic screening to reduce the risk of CBAVD and cystic fibrosis in offspring.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: Immunoglobulin A nephropathy (IgAN) is one of the most common types of kidney disease, and kidney transplantation is the most effective treatment for end-stage renal disease. This study aims to analyze the clinical curative effect of renal transplantation for adults with IgAN and to discuss the efficacy and safety of kidney transplantation for IgAN at the perioperative period and medium- and long-term follow-up. Methods: This retrospective study included the clinical and follow-up data of 81 adult patients with IgAN who underwent kidney transplantation at the Second Xiangya Hospital, Central South University from January 2018 to January 2022. Of the 81 patients whose age at (34.1±9.9) years old, 47 (58.0％) were male. The body mass index was (20.8±3.2) kg/m2, and the human leukocyte antigen (HLA) mismatch number was 3.5±1.2. The estimated glomerular filtration rate (eGFR) and daily 24-hour urine output for the recipients on the 1st, 5th, and 7th day after kidney transplantation and when they were discharged were analyzed. The recovery of the transplanted kidney and occurrence of complications were comprehensively evaluated. The eGFR, urinary protein, and occult blood were evaluated at the 6th, 12th, 24th, 36th, and 48th month and at the last follow-up. Results: The follow-up time was (25.7±15.8) months. No primary non-function occurred in any patient during the perioperative period time. Fifty-one (63.0％) patients had immediate graft function recovery, and 16 (19.8％) patients had slow graft function recovery. Delayed recovery of graft function was observed in 14 (17.3％) patients. A total of 19 perioperative complications occurred, including 9 patients with acute rejection, 5 patients with urinary fistula, 1 thrombosis in both lower limbs, and 4 lymphatic fistula. The eGFR at 6th, 12th, 24th, 36th, and 48th month of follow-up were (65.3±22.9), (67.6±23.0), (64.3±21.8), (65.9± 24.7), and (68.7±31.2) mL/(min·1.73 m2), respectively. The eGFR remained high during the medium- and long-term follow-ups. At the longest follow-up of 56 months, eGFR fluctuation was still mild, and the positive rate of urine protein and occult blood was low. IgAN recurred in 4 transplanted kidneys, accounting for 4.94％ of the total patients, without severe renal insufficiency. Three patients had kidney dysfunction due to severe pneumonia, rejection, and stone in the transplanted kidney. The overall survival rate of the transplanted kidney was higher than 95％, and the survival rate of all patients was 100％ till Januray 2022. Conclusion: Renal transplantation for adults with IgAN had a remarkable short-term effect. The recipients can be beneficial significantly to favorable midium- and long-term outcomes. IgAN recurrence is infrequent and rarely causes severe renal function damage.

OBJECTIVE: To explore the genetic basis for 4 patients with globozoospermia. METHODS: Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing. RESULTS: All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region. CONCLUSION DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.
Male ; Humans ; Teratozoospermia/genetics* ; Homozygote ; Semen ; Sequence Deletion ; 3' Untranslated Regions ; Membrane Proteins

Objective:To explore the clinical efficacy of adult donor dual kidney transplantation.Methods:Retrospective analysis of case data of 13 adult donor kidney dual kidney transplantation (DKT) performed in the The Second Xiangya Hospital of Central South University from September 2016 to December 2020. For 13 donors, the average age and BMI were (53.5±12.4)years and (24.3±2.8) kg/m 2, respectively. Their mean Serum creatinine (SCr) at admission and before procurement was (132.9±54.1)and (228.7±112.4)μmol/L, respectively. 3 of them had diabetes mellitus history, and 8 had hypertension history. 11 met the United Network for Organ Sharing (UNOS) DKT criteria and 6 met Remuzzi score DKT criteria. For 13 recipients, the average age and BMI were (39.3±8.9)years and (20.2±2.4)kg/m 2, respectively. All of them received ABO blood type-matched kidney transplants. 2 of them had their grafts transplanted in the bilateral iliac. In 12 cases, the grafts filled rapidly and urinated immediately when opening blood flow. In 1 case, the grafts were dark in color and vascular showed weak pulsation after opening blood flow. The time to recovery of perioperative graft function (from the day of surgery to the natural reduction of SCr to the normal range 44-133μmol/L), the occurrence of delayed graft function (DGF), acute rejection (AR), ureteral and surgical incision complications, as well as the recipients’ final follow-up SCr, eGFR, urinary protein, and grafts outcome were observed. Risk factors affecting outcomes were assessed by univariate logistic regression analysis. Results:The SCr dropped to the normal range at discharge in 10 recipients, and the average recovery time was (13.8±13.0) days. In other 3 cases SCr at discharge were 300.0, 149.0, 152.5μmol/L. 4 cases had DGF, 4 had AR, 1 experienced urinary fistula, and 1 experienced incisional dehiscence, which were treated with anti-rejection, J-tube implantation, continuous catheterization to maintain bladder void, secondary suturing, respectively. The follow-up time ranged from 4 to 54 months, with a median of 28(15.5, 31.0) months. At the final follow-up time, 10 cases had good graft function, 2 suffered impaired kidney function, and 1 experienced graft failure. The average SCr and eGFR except for graft failure patient were (144.2±101.3)μmol/L and (52.9±21.2)ml/min, respectively. 4 had positive urine protein. Univariate logistic regression analysis showed that donor age, BMI, history of diabetes mellitus and hypertension, and SCr were not significantly correlated with recipients’ DGF and graft impairment ( P>0.05), and due to the small sample size, multifactorial logistic regression analysis was not performed. Conclusion:The short to medium-term effects of adult donor DKT coule be safe and feasible.

Objective:To study the expression of miRNA-29c in type 1 diabetic patients with early nephropathy and its diagnostic value for early nephropathy.Methods:168 patients with type 1 diabetes who were treated in our hospital from Jan. 2019 to Mar. 2022 were retrospectively selected as the research subjects. According to the occurrence of nephropathy, they were divided into simple diabetes group (122 cases) and diabetic nephropathy group (46 cases). Serum miRNA-29c levels were detected by RT-PCR. The gender, age, course of disease, and serum miRNA-29c levels were compared between the two groups. Logistic regression was used to analyze the influencing factors of early nephropathy in patients with type 1 diabetes. The ROC curve was used to analyze the diagnostic value of miRNA-29c for early nephropathy in type 1 diabetes.Results:The course of disease, blood pressure (systolic blood pressure, diastolic blood pressure), HbA1c, TC and blood uric acid in early nephropathy group were higher than those in simple diabetes group, while albumin, total bilirubin and miRNA-29c were lower than those in simple diabetes group, and the difference was statistically significant ( P<0.05). Multivariate Logistic analysis showed: long disease duration ( OR=2.061, 95% CI=1.090-3.896), systolic blood pressure ( OR=1.143, 95% CI=1.023-1.279), diastolic blood pressure ( OR=1.151, 95% CI=1.022) -1.298), high HbA1c ( OR=1.317, 95% CI=1.049~1.653), high blood uric acid ( OR=1.306, 95% CI=1.028-1.659), low miRNA-29c ( OR=0.845,95% CI= 0.730-0.979) were the risk factors for early nephropathy in patients with type 1 diabetes ( P<0.05). ROC curve analysis showed that the cut-off value of miRNA-29c for the diagnosis of early renal disease was 0.952, the area under the curve (AUC) was 0.863 (95% CI: 0.801-0.925), and the sensitivity and specificity were 84.78% and 80.33%, respectively. Conclusion:Serum miRNA-29c in patients with early stage nephropathy of type 1 diabetes is in a low expression state, which is an influencing factor for early stage nephropathy in patients with type 1 diabetes, and has a good diagnostic value for early stage nephropathy.

Objective:To investigate the correlation between the prognosis of patients infected with BK virus after renal transplantation and their peripheral blood related indexes.Methods:131 patients from the Renal Transplantation Department of the Second Xiangya Hospital of Central South University who underwent renal transplantation and firstly infected with BK virus after the surgery during the period from August 2018 to August 2021 were retrospectively analyzed. 93 males (71.0%) and 38 females (29.0%). The average age was (37.5±11.3) years old. 109 cases underwent cadaveric kidney transplant (83.2%) and 22 cases underwent relatives kidney transplant (16.8%). The onset time of the first infection with BK virus after renal transplantation was (188.7±16.6) days, and the serum creatinine was (127.5±39.5) μmol/L. 25 patients (19.1%)infected with BK virus were positive in blood and urine at the same time, and 106 patients (80.9%)infected with BK virus were positive only in urine. Among 131 patients infected with BK virus, 70 patients were treated by lowering the blood concentration of tacrolimus to enhance immunity, 12 patients were treated by switching tacrolimus to cyclosporine, and 49 patients had incomplete follow-up data. The DNA load of BK virus in 25 patients [5.6(2.4, 12.3)×10 3copies/ml] positive in blood, white blood cell count(WBC)(5.8±2.0)×10 9/L, hemoglobin(Hb)(122.0±22.4)g/L, platelet count(PLT)(187.1±63.1)×10 9/L, neutrophil count(NEUT)(3.9±1.7)×10 9/L, lymphocyte count(LYM)(1.5±0.8)×10 9/L, monocyte count(MONO)(0.4±0.2)×10 9/L, neutrophil to lymphocyte ratio(NLR)2.2(1.7, 3.5), derived neutrophil to lymphocyte ratio(dNLR)1.7(1.3, 2.6), platelet to lymphocyte ratio(PLR)121.3(86.3, 227.3), monocyte to lymphocyte ratio(MLR)0.2(0.1, 0.4) and lymphocyte to monocyte ratio(LMR)4.7±2.6. The DNA load of BK virus in 106 patients [20.4(0.4, 2 570.0)×10 5copies/ml] positive in urine, WBC 6.6(4.8, 9.1)×10 9/L, Hb(129.0±24.5)g/L, PLT 188.0(147.3, 226.5)×10 9/L, NEUT 4.6(3.0, 6.6)×10 9/L, LYM(1.7±0.8)×10 9/L, MONO 0.4(0.3, 0.5)×10 9/L, NLR 2.8(1.9, 3.9), dNLR 2.1(1.5, 3.0), PLR 120.5(87.0, 163.2), MLR 0.2(0.1, 0.4), LMR 4.5(2.8, 6.7). 70 patients infected with BK virus treated by lowering the blood concentration of tacrolimus were divided into BK virus rise group and BK virus decline group according to the change of BK virus DNA load in blood and urine before and after treatment (the grouping principle of this study gives priority to the change of BK virus DNA load in blood, followed by the change of BK virus DNA load in urine). The WBC, Hb, PLT, NEUT, LYM, MONO, NLR, dNLR, PLR, MLR, LMR, tacrolimus blood concentration and change difference, blood creatinine and change difference were analysed between two groups. Results:The BK virus DNA load in 25 patients positive in blood was correlated with NLR and dNLR ( r=0.5062, P=0.0098; r=0.5738, P=0.0027), and there was no correlation between the BK virus DNA load in blood with the WBC ( r=-0.0185, P=0.9302), Hb ( r=0.0912, P=0.6646), PLT ( r=-0.3931, P=0.0519), NEUT ( r=0.2438, P=0.2401), LYM ( r=-0.3035, P=0.1402), MONO ( r=-0.3279, P=0.1096), PLR( r=0.1054, P=0.6161), MLR( r=0.0738, P=0.7257), LMR( r=-0.0738, P=0.7257). There was no correlation between the BK virus DNA load in 106 patients positive in urine and WBC( r=0.0222, P=0.8209), Hb( r=-0.0323, P=0.7423), PLT( r=0.0847, P=0.3881), NEUT( r=0.0417, P=0.6713), LYM( r=0.0010, P=0.9916), MONO( r=0.0224, P=0.8196, NLR( r=0.0170, P=0.8623), dNLR ( r=-0.0013, P=0.9892), PLR( r=0.0387, P=0.6934), MLR( r=-0.0070, P=0.9433)and LMR( r=0.0070, P=0.9433). As for 70 patients infected with BK virus, there were 37 patients in the BK virus rise group and 33 patients in the BK virus decline group. In the two groups, age [(38.4±12.0)years old and(39.0±9.0)years old], gender [male /female: (23/14) cases and(27/6)cases], blood type [A+ /B+ /AB+ : (22/13/20)cases and (26/6/1)cases], donation type [relatives donnation/cadaveric donation: (29/8)cases and (27/60)cases], blood creatinine(after treatment)[123.0(98.4, 140.5)μmol/L and 132.0(107.1, 162.4)μmol/L] and change difference before and after treatment [0(-15.7, 10.5)μmol/L and -2.0(-9.1, 15.0)μmol/L], tacrolimus blood concentration (after treatment)[(6.7±2.0)ng/ml and(6.5±1.5)ng /ml] and tacrolimus concentration change difference [-1.4(-3.8, 0.6)ng/ml and -1.2(-2.2, 1.3)ng/ml] had no significant difference( P<0.05). The MONO of the two groups was statistically different [0.3(0.2, 0.5)×10 9/L and 0.4(0.3, 0.6)×10 9/L, P=0.033], and there was no difference between the two groups in WBC[6.6(4.1, 8.8)×10 9/L and 6.8(5.4, 8.9)×10 9/L], Hb[(133.2±25.3)g/L and(131.6±20.6)g/L], PLT[185.0(151.0, 231.5)×10 9/L and 196.0(149.0, 234.0)×10 9/L], NEUT[4.3(2.4, 6.4)× 10 9/L and 4.2(3.1, 5.5)×10 9/L], LYM[1.7(1.1, 2.2)×10 9/L and 1.8(1.1, 2.3)×10 9/L], NLR[2.5(1.9, 3.8)and 2.4(1.9, 3.7)], dNLR [2.0(1.5, 2.8)and 1.9(1.4, 2.5)], PLR [114.9(85.1, 159.4)and 111.3(77.1, 159.6)], LMR(4.6±2.6 and 5.2±2.4), MLR[0.2(0.2, 0.4)and 0.2(0.2, 0.4)]( P<0.05). Conclusions:There is a positive correlation between the blood BK virus DNA load and NLR, dNLR in renal transplant recipients infected with BK virus. The rise of MONO correlates with good prognosis of BK virus.

The effect of living kidney transplantation between identical twins is satisfied, but it is rarely reported. From October 2019 to February 2021, two recipients received kidney transplantation from their twin sisters in the Second Xiangya Hospital of Central South University. The primary disease of the two recipients was acute glomerulonephritis in 1 case and diabetic nephropathy in 1 case. Two recipients received tacrolimus/cyclosporine+ mortemycophenol ester+ methylprednisolone after surgery. The patients were followed up for 3.0 and 1.5 years, respectively, with renal function recovering well.

Objective: To analyze genetic variant in a pedigree affected with congenital high myopia. Methods: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. Results: WES has identified a novel splice site heterozygous variant (c.2556+ 1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+ 1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+ PM2). Conclusion A novel splice variant (c.2556+ 1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.

OBJECTIVE: To analyze genetic variant in a pedigree affected with congenital high myopia. METHODS: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. RESULTS: WES has identified a novel splice site heterozygous variant (c.2556+1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+PM2). CONCLUSION A novel splice variant (c.2556+1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.
Collagen Type XI ; genetics ; Genetic Testing ; Heterozygote ; Humans ; Myopia ; genetics ; Pedigree ; Whole Exome Sequencing