OBJECTIVE: To carry out prenatal diagnosis for a fetus with normal ultrasonographic finding at 20 weeks' gestation but a copy number variant(CNV) of 13q indicated by non-invasive prenatal test (NIPT). METHODS: Karyotyping analysis and chromosomal CNV assay were carried out on the amniotic fluid sample. Parental peripheral blood sample was collected for chromosomal analysis. Detailed fetal ultrasound scan was carried out to rule out structural abnormalities of the fetus. RESULTS: The fetus was detected with a heterozygous 10.14 Mb deletion at 13q21.1q21.32, which has originated from the phenotypically normal mother. No apparent karyotypic abnormality was detected in the fetus and its parents. No ultrasonic abnormality was found in the fetus. CONCLUSION Both the fetus and its mother have carried a heterozygous 10.14 Mb deletion at 13q21.1q21.32 and presented normal phenotypes.Combined with literature review, the segmental deletion was judged to be a benign variant.
Female ; Genetic Counseling ; Humans ; Karyotyping ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

Objective:To evaluate the safety and efficacy of daratumumab in the treatment of multiple myeloma (MM).Methods:The clinical data of 19 MM patients treated with daratumumab alone or in combination with chemotherapy regimens from June 2021 to December 2021 in the Affiliated Hospital of Jining Medical College were retrospectively analyzed, of which 2 patients received daratumumab alone, 6 cases received daratumumab combined with lenalidomide+dexamethasone (DRD) regimen, 1 case received daratumumab combined with liposomal doxorubicin+dexamethasone (DVD) regimen, 2 case received daratumumab combined with dexamethasone+cyclophosphamide+etoposide+cisplatin (DECP) regimen, 3 cases received daratumumab combined with isazomib+dexamethasone (ID) regimen, 2 cases received daratumumab combined with bortezomib+dexamethasone (BD) regimen, and 3 cases received daratumumab combined with dexamethasone (DD) regimen. The efficacy and incidence of adverse effects were analyzed.Results:Among the 19 patients, 8 had complete remission (CR), 1 had very good partial remission (VGPR), 5 had partial remission (PR), 1 had stable disease (SD), and 4 had progressive disease (PD). The overall response rate (ORR) was 73.7% (14/19). The median progression-free survival (PFS) time was 10.42 months (95% CI 8.04-12.79 months) and the median overall survival (OS) time was 52.06 months (95% CI 37.85-66.27 months). The main adverse reactions during treatment were grade 3 neutropenia in 3 cases, grade 3 lymphopenia in 3 cases, grade 2 anemia in 5 cases, grade 2 nausea and vomiting in 7 cases, and infusion-related adverse reactions in 7 cases. Conclusions:Daratumumab-based chemotherapy regimens for the treatment of MM patients can achieve great efficacy with good safety and tolerability.

Objective:To investigate the efficacy and safety of ixazomib-based therapy for multiple myeloma.Methods:The data of 32 patients with multiple myeloma treated with isazomib-based regimen in the Affiliated Hospital of Jining Medical University from December 2020 to December 2021 were retrospectively analyzed. Among 32 patients, 17 cases were relapsed/refractory, and the remaining 15 cases had initial treatment. The treatment regimens included ID (isazomib + dexamethasone), IRD (isazomib + lenalidomide + dexamethasone) and ICD (isazomib + cyclophosphamide + dexamethasone). The short-term curative effect and adverse reactions of relapsed/refractory patients and patients at initial onset were analyzed.Results:The overall response rate (ORR) of relapsed/refractory patients was 52.9% (9/17), of which 6 cases achieved complete remission (CR), 2 cases achieved very good partial remission (VGPR) and 1 case achieved partial remission (PR). The ORR of refractory patients receiving bortezomib therapy was 40.0% (4/10). The ORR of patients at initial onset who could be evaluated the curative effect was 100.0% (14/14), including 9 cases of CR, 2 cases of VGPR and 3 cases of PR. After treatment, 2 patients (6.2%) had grade Ⅲ-Ⅳ adverse events (1 case of herpes zoster and 1 case of thrombocytopenia), and none of the patients had grade Ⅲ-Ⅳ peripheral neuropathy.Conclusion:Isazomib is effective and safe in the treatment of initially treated and relapsed/refractory multiple myeloma.

OBJECTIVE: To explore the genetic etiology in four patients with hyperbilirubinemia, and discuss the correlation between clinical characteristics and molecular basis. METHODS: The data of clinical manifestation and auxiliary examinations were collected. Genomic DNA of the four patients was extracted and analyzed by next-generation sequencing using the panel including genes involved in hereditary metabolic liver diseases. Suspected variants were verified by Sanger sequencing. RESULTS: All of the four patients were males with normal liver enzymes. It was revealed that all the patients had heterozygous variants, among which c.3011C>T, c.2443C>T and c.2556del were the variants which have not been reported previously. CONCLUSION All of the patients were diagnosed as Dubin-Johnson syndrome (DJS) caused by ABCC2 gene variants. The novel variants add to the spectrum of genetic variants of the disease. Because of the favorite prognosis, precise diagnosis can greatly reduce the psychological pressure of patients and avoid excessive treatments. At the same time, it could provide pertinent genetic counseling for the families.
DNA ; Female ; Heterozygote ; Humans ; Jaundice, Chronic Idiopathic/genetics* ; Male ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Phenotype

Objective:To investigate the clinical efficacy of autologous peripheral blood hematopoietic stem cell transplantation (HSCT) in treatment of lymphoma.Methods:The clinical data of 41 lymphoma patients undergoing autologous peripheral blood HSCT at the Affiliated Hospital of Jining Medical University between January 2014 to December 2020 were retrospectively analyzed. There were 6 cases of Hodgkin lymphoma and 35 cases of non-Hodgkin lymphoma. The mobilization regimens included chemotherapy drugs + granulocyte colony-stimulating factor (G-CSF) + thrombopoietin (TPO) or chemotherapy drugs + G-CSF. The pre-conditioning schemes before transplantation were listed as follows: BEAM (mustine + cytarabine + etoposide + melphalan) regimen + decitabine in 26 patients, BEAM regimen in 12 patients, BEAM regimen + chidamide in 3 patients. The progression-free survival (PFS), overall survival (OS), related complications, prognoses after transplantation were observed. The effects of clinical staging, B symptom,International Prognostic Score Index (IPI), extranodal involved sites, hemoglobin (Hb), lactic dehydrogenase (LDH), β 2-microglobulin (β 2-MG), transplantation regimen and the status before transplantation on PFS and OS after transplantation were evaluated. Results:Among 41 patients, 37 patients (90.24%) achieved complete remission (CR), 2 patients (4.88%) achieved partial remission (PR) and 2 patients loss assessment data (4.88%) before autologous peripheral blood HSCT. The median karyocyte count was 12.74×10 8 /kg [(3.91-22.68)×10 8/kg] in 24 patients with the complete data of stem cell collection, the median CD34 positive cell count was 6.74×10 6/kg [(0.91-50.47)×10 6/kg]. All 41 patients had hematologic reconstruction. The median time of platelet implantation was 11 d (7-32 d) and the median time of granulocyte implantation was 9 d (8-16 d). All patients achieved CR after transplantation and no one case had transplantation-related death. By the end of follow-up, 33 cases (80.49%) had no progression of disease, 8 cases (19.51%) died. The OS rates of 12-month, 24-month and 72-month were 93.4%, 85.3% and 60.9%, respectively after transplantation. The PFS rates of 12-month, 24-month and 72 month were 93.3%, 84.0% and 84.0%, respectively. Median PFS and OS had not been reached. There were no statistically significant differences in the PFS and OS of patients with different gender, clinical staging, B symptom, IPI score, extranodal involved sites, Hb, LDH, β 2-MG and the status before transplantation(all P > 0.05) . The PFS and OS of patients receiving BEAM regimen + decitabine were better than those of patients receiving BEAM regimen alone (all P < 0.05). Conclusions:Autologous peripheral blood HSCT is effective in treatment of lymphoma. Moreover, BEAM regimen + dicitabine preconditioning regimen can achieve longer survival time compared with BEAM regimen alone.

Porphyromonas gingivalis peptidylarginine deiminase (PPAD), an isoenzyme of animal endogenous peptidylarginine deaminase, is secreted by the Por system and catalyzes the citrullination of arginine. Recent studies have found that PPAD can affect the formation of Porphyromonas gingivalis biofilm and reduce the body′s immune defense function, which is related to the occurrence and development of many diseases such as periodontal diseases and rheumatoid arthritis. In this paper, we reviewed the molecular characteristics of PPAD, including the genetic and functional characteristics, as well as the mechanisms related to the inflammatory and autoimmune diseases. We also pointed some issues that should be pay attention to in the further study.

OBJECTIVE: To carry out genetic analysis for a family with a fetus manifesting bilateral polycystic renal dysplasia and oligohydramnios at 16 gestational week and a previous history for fetal renal anomaly. METHODS: Ultrasound scan was carried out to detect the morphological changes. Following genetic counselling, the parents had decided to terminate the pregnancy. Fetal kidneys were subjected to histological examination. Target capture and next generation sequencing (NGS) was applied to the abortus to detect potential variants. The results were verified by Sanger sequencing. RESULTS: Histological examination of fetal kidneys revealed cystic changes without cortex, medulla or normal renal structure. NGS has identified a heterozygous c.100+1G>A variant and deletion of exon 3 of the INVS gene, which were respectively inherited from the mother and father. CONCLUSION Through NGS and Sanger sequencing, the fetus was diagnosed with type II nephronophthisis (NPHP2). Above result can provide guidance for further pregnancy and enforce understanding of clinical features and genetic etiologies for NPHP.
Female ; Fetus ; Genetic Testing ; Heterozygote ; Humans ; Mutation ; Polycystic Kidney, Autosomal Dominant ; diagnostic imaging ; genetics ; Pregnancy ; Sequence Deletion ; genetics ; Transcription Factors ; genetics ; Ultrasonography

OBJECTIVE: To explore the genetic etiology of three pedigrees with a gestational history of fetal renal anomalies. METHODS: Peripheral venous blood or skin samples were derived from the probands of the three pedigrees. Copy number variation sequencing (CNV-seq) was applied to detect alterations of genome CNVs. RESULTS: The patient from pedigree 1 and the fetuses from pedigrees 2 and 3 all carried a heterozygous 17q12 deletion, with the size ranging from 1.4 Mb to 1.48 Mb encompassing the HNF1B gene. CONCLUSION The diagnosis of 17q12 microdeletion may be difficult during fetal period for its variable phenotypes. Alterations of chromosomal copy numbers need to be excluded in such patients.
Chromosome Deletion ; Chromosomes, Human, Pair 17 ; genetics ; DNA Copy Number Variations ; Fetus ; Genetic Testing ; Hepatocyte Nuclear Factor 1-beta ; genetics ; Humans ; Pedigree ; Phenotype

Objective: The phenotype and genetics of three patients with autosomal recessive polycystic kidney disease (ARPKD) at childhood, teenage and advanced age were analyzed. Methods: Next generation sequencing (NGS) was applied to all the probands. PCR and Sanger sequencing were used to verify the suspicious gene variants screened by NGS in the probands and their family members, and one of the family got prenatal diagnosis. Results: Through NGS, PCR and Sanger sequencing, the 5-yr proband in pedigree 1 was shown to carry compound heterozygous variants of c. 5935G>A(p.G1979R) and c. 5428G>T(p.E1810X) of PKHD1, originated from his parents; In pedigree 2, the 17-ys proband was detected with c. 5512T>C(p.Y1838H) and c. 5935G>A(p.G1979R) variants of PKHD1 orginated from her parents, and her mother also got prenatal diagnosis during the second trimester; In pedigree 3, the 70-ys female proband was found with variants c. 11314C>T (p.R3772X) and c. 3860T>G (p.V1287G) of PKHD1. Conclusion The three pedigrees were diagnosed as ARPKD caused by PKHD1 variants. Five types of variants were detected, c. 5935G>A and c. 11314C>T were the known pathogenic variants, while c. 5512T>C, c. 5428G>T and c. 3860T>G were not reported previously. Considering the complexity of the genetics and phenotypes of the cystic renal diseases, genetic diagnosis is crucial to give accurate etiological diagnosis, which may benefit the clinic management.

OBJECTIVE:To provide reference for hospital infection treatment and control. METHODS:The etiological data of Enterococcus isolated from clinical specimens were collected from our hospital during Jan. 2009-Jun. 2017. The drug resistance of commonly used antibiotics and infection related risk factors were analyzed retrospectively. RESULTS:A total of 6252 isolates of Enterococcus were isolated,of which there were 1994 strains of E. faecalis and 3575 strains of E. faecium. The bacteria were mainly isolated from urine(2009 strains),drainage liquids(1538 strains),bile(1168 strains),wound secretions(561 strains), blood (493 strains). The detection rate increased 9.4％ in 2009 to 13.4％ in 2017. Resistance rate of E. faecalis to ampicillin, penicillin and vancomycin showed a wavelike decrease,and E. faecalis showed low resistance rate to vancomycin,teicoplanin, linezolid and tigecycline. Resistance rate of E. faecalis to ciprofloxacin,moxifloxacin and levofloxacin decreased wavily to 2014 but showed a fluctuating upward trend since 2015. Resistance rate of E. faecium to linezolid decreased from 1.9％ in 2009 to 0.2％ in Jun. 2017;resistance rate of E. faecium to vancomycin and teicoplanin continues to fluctuate,but it is still at a low level;resistance rate of E. faecium to tetracycline decreased, but that to high concentration gentamicin increased. There were 43 strains of vancomycin-resistant E. faecium and 8 trains of vancomycin-resistant E. faecalis detected in 51 patients. Resistant rates of vancomycin-resistant E. faecium to linezolid,tigecycline and teicoplanin were 23.3％,0,35.3％,respectively. Resistant rates of vancomycin-resistant E. faecalis to linezolid,tigecycline and teicoplanin were 0. Pearson relationship analysis showed that days in ICU (r=0.225,P<0.01),tracheotomy or intubation (r=0.314,P<0.01),days of antibiotic use (r=0.347,P<0.01),types of antibacterial drugs (r=0.226,P<0.01),use of glucocorticoids (r=0.190,P<0.01),and days of carbapenems use (r=0.173,P<0.05)were positively correlated with vancomycin-resistant E. faecium infection rate and vancomycin-resistant E. faecalis infection rate. CONCLUSIONS:The detection rate of Enterococcus in our hospital is fluctuating upward. E. faecalis and E. faecium were the main types,mainly from urine and drainage fluids. The resistance rate of Enterococcus most of antibiotics shows a downward trend. The resistance rate of E. faecium to high concentration gentamycin is on the rise,while that of E. faecium to linezolid and tetracycline is decreased. The appropriate antibiotics should be selected according to the patient's condition and drug susceptibility results.