OBJECTIVE: To explore the genetic etiology for a pregnant woman with a history of multiple adverse pregnancies and assess the phenotype-genotype correlation of 22q11.2 microduplication syndrome in her family. METHODS: Amniotic fluid sample was taken from a pregnant woman for whom non-invasive prenatal screening indicated chromosome 22 abnormalities in the fetus. Peripheral blood samples from the woman, her brother and parents were collected for high-throughput low-depth whole genome sequencing (CNV-seq). A pedigree traceability analysis of the results was conducted in conjunction with analysis of clinical manifestation. Relevant literature (from establishment to March 2025) was systematically searched. This study was approved by the Medical Ethics Committee of Mianyang Maternal and Child Health Care Hospital (Ethics No.: Lun Shen [2024]009). RESULTS: CNV-seq revealed that the fetus had harbored a 6.02 Mb duplication at 22q11.21q11.23. Karyotyping confirmed it as 46,X?dup(22)(q11.2). Pedigree verification demonstrated that the pregnant woman, her brother and mother had all carried the same duplication. Phenotypic analysis of the affected family members showed classic features of 22q11.2 microduplication syndrome, including hypernasal speech, low nasal bridge, congenital heart disease, and cognitive impairment. A total of 44 cases with full information (including three patients from this pedigree) were included in the analysis. The penetrance of 22q11.2 duplication was approximately 29.5% (13/44), and 52.3% (23/44) of the cases had inherited the variant from a phenotypically normal parent. CONCLUSION This study has identified the genetic basis for the woman's recurrent adverse pregnancies and phenotypic abnormalities in her family members. The scoliosis identified in her younger brother has not been previously reported, thereby may enrich the clinical phenotype of this syndrome. For fetuses identified with a 22q11.2 microduplication, detailed fetal imaging is recommended, and genetic counseling should be provided to the couples.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; Chromosome Duplication/genetics* ; Male ; Pedigree ; DiGeorge Syndrome/diagnosis* ; Adult ; Chromosomes, Human, Pair 22/genetics* ; Abnormalities, Multiple

Objective:To investigate the value of elevated preoperative troponin T (TnT) in predicting perioperative adverse cardiac events in geriatric hip fracture patients.Methods:A total of 273 elderly patients undergoing surgical treatment for hip fracture at Department of Cardiology, Tianjin Hospital between January 2024 and December 2024 were enrolled. Basic demographic information was recorded, and preoperative TnT levels were measured. Patients with elevated preoperative TnT ( n=114) were enrolled into the elevated group, while those with normal TnT ( n=159) were enrolled into the normal group. Fracture types included femoral neck fracture ( n=141) and intertrochanteric fracture ( n=132). The impact of elevated preoperative TnT on perioperative major adverse cardiovascular events (MACEs), as well as the influence of different fracture types on MACEs, were analyzed. Normally distributed continuous data were expressed as Mean±SD and compared by independent samples t-test. Categorical data were expressed as case(%) and compared by χ2 test. Multivariate binary logistic regression analysis was performed. The predictive value of TnT for MACEs was assessed by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results:The incidence of perioperative MACEs was significantly higher in the elevated TnT group (21.9%, 25/114) compared to the normal TnT group (3.1%, 5/159), with a statistically significant difference ( χ2=23.95, P<0.001). The comparison of postoperative MACEs incidence between different fracture types showed no statistically significant difference [12.1% (17/141) vs. 9.8% (13/132)] ( χ2=0.34, P=0.560). Multivariate binary logistic regression analysis indicated that elevated TnT level ( OR=8.633, 95% CI: 3.117-23.911, P<0.001) was an independent risk factor for perioperative major adverse cardiovascular events (MACEs), increasing the risk by 7.633 times compared to patients with normal TnT. A TnT threshold of ≥0.028 μg/L predicted MACEs with a sensitivity of 0.600 and specificity of 0.954 (AUC=0.839, 95% CI: 0.751-0.926, P<0.05). Conclusion:Troponin T can serve as an independent predictor of perioperative adverse cardiovascular events in elderly patients undergoing surgery for hip fracture and plays a crucial role in the perioperative cardiovascular risk assessment of these patients.

OBJECTIVES: This study aimed to construct a risk prediction model for the occurrence of the demora-lization syndrome in patients with oral cancer and provide a scientific basis for the prevention of this syndrome in patients with oral cancer and the development of personalized care programs. METHODS: A total of 486 patients with oral cancer in West China Hospital of Stomatology of Sichuan University and Sun Yat-sen Memorial Hospital of Sun Yat-sen University from 2024 March to July were selected by convenience sampling. We integrated clinical data and evidence from previous studies to identify the key variables affecting the demoralization syndrome in patients with oral cancer. The 486 patients were divided into a training set and a validation set in an 8∶2 ratio. A clinical risk prediction model was established based on the individual data of 365 patients in the development cohort. Through least absolute shrinkage and selection operator (LASSO) regression, a moderate to severe risk prediction model of demoralization syndrome in oral cancer was constructed, and a clinical machine-learning nomogram was constructed. Bootstrap resampling was used for internal validation. The data of 121 patients in the validation cohort were externally validated. RESULTS: The incidence of the demoralization syndrome in patients with oral cancer was 405 cases (83.3%), of which 279 cases (57.4%) were mild, 176 cases (36.2%) were moderate, and 31 cases (6.4%) were severe. The core model, including patient education level, disease understanding, and MDASI-HN score, was used to predict the risk of outcome. Internal validation of the model yielded C statistic of 0.783 6 (95% CI: 0.78-0.87), beta of 0.843 4, and calibration intercept of -0.040 6. Through external validation, the validation set C statistic was 0.80 (95%CI: 0.71-0.87), beta was 0.80, and calibration intercept was -0.08. CONCLUSIONS Our risk prediction mo-del of the demoralization syndrome in patients with oral cancer performed robustly in validation cohorts of different nur-sing environments. The model has good correction and good discrimination and can be used as an evaluation and prediction item at admission.
Humans ; Mouth Neoplasms/complications* ; Male ; Female ; Nomograms ; Middle Aged ; Syndrome ; Aged ; Adult ; Risk Factors ; Risk Assessment ; Machine Learning

ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi， so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） combined with Smart aroma database and National Institute of Standards and Technology（NIST） database were used to characterize the aroma components in different parts of N. jatamansi， and the aroma components were quantified according to relative response factor（RRF） and three internal standards， and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis（OPLS-DA） and cluster thermal analysis based on variable importance in the projection（VIP） value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose， and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data， and the rapid identification model of different parts of N. jatamansi was established by principal component analysis（PCA）， discriminant factor alysis（DFA）， soft independent modeling of class analogies（SIMCA） and statistical quality control analysis（SQCA）. ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi， of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components， the contents of five components（ethyl isovalerate， 2-pentylfuran， benzyl alcohol， nonanal and glacial acetic acid，） in the aboveground part of N. jatamansi were significantly higher than those in the underground part（P<0.01）， the contents of β-ionone， patchouli alcohol， α-caryophyllene， linalyl butyrate， valencene， 1，8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part（P<0.01）. Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82， and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted， respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%， the validation score of the SIMCA model for discrimination of the two parts was 99， and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose（PCA， DFA， SIMCA and SQCA） can realize the rapid identification of different parts of N. jatamansi. Combining the two results， it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.

Objective:To investigate the pattern of Mesothelin(MSLN)-specific T-cell(CTLs)immune reconstitution after allogeneic hematopoietic stem cell transplantation.Methods:Two cases of Mesothelin-positive patients with acute myeloid leukemia(AML)were screened,and the number of MSLN-CTLs and its subpopulations,the expression of surface PD-1/CTLA-4/TIM-3 im-mune exhaustion molecules,and the functions of secreted cytokines TNF-α and IFN-γ were monitored by flow cytometry after trans-plantation.They were compared with WT1-CTLs and cytomegalovirus(CMV)CTLs.Meanwhile,the relationship between CTL recon-stitution and Minimal residual disease(MRD)and leukemia recurrence was analyzed.Results:After transplantation,MSLN-CTLs,WT1-CTLs and CMV-CTLs can be detected,and intracellular factors were secreted.The phenotypes of WT1 specific CD8+T cells,MSLN specific CD8+T cells and CMV specific CD8+T cells were mainly TEM subsets and TEMRA subsets,and the TEM subsets of CMV specific CD8+T cells were more obvious.Compared with CMV-CTLs,the proportions of T Naive,TCM and TEMRA subsets were relatively higher in MSLN-specific CD8+T cells and WT1-specific CD8+T cells,and the expression levels of PD-1,CTLA-4 and TIM-3 were higher in MSLN-CTLs and WT1-CTLs.The dynamic changes of MSLN-CTLs and WT1-CTLs after transplantation were related to leukemia load and the chimerism rate of donor and recipient.Conclusion:After allogeneic hematopoietic stem cell transplantation,im-mune recovery to MSLN is found,which is different from WT1-CTLs and CMV-CTLs.

Objective:To investigate the protection effect of a new 360-degree radiation protection and position fixation device on the pelvic cavity during chest CT examination.Methods:Three shielding methods were applied to the pelvic cavity of the standard simu-lated human model,i.e.,no shielding(group A),traditional 180-degree front protection with a lead square towel(group B),and 360-degree protection with a new protection device(group C).Philips IQon Spectral CT was used to perform chest CT scan at a tube voltage of 80 kVp,100 kVp,and 120 kVp,respectively,and the cumulative radiation doses from the front,side,and back of the pelvic cavity were measured and analyzed statistically.Results:Compared with groups A and B,group C had significantly lower cumulative radiation doses of the front,side,and back of the pelvic cavity in the simulated human model(all P<0.05);at the tube voltages of 80,100,and 120 kVp,the cumulative dose of the pelvic cavity in group C was reduced by 85%,84%,and 67%,respectively,compared with that in group B,and was reduced by 88%,87%,and 76%,respectively,compared with that in group A.Compared with group A,group B had significant reductions in the radiation doses of the side and back of the pelvic cavity(P<0.05)and a significantly higher radiation dose of the front of the pelvic cavity,which was increased by 19%,23%,and 10%,respectively,at the tube voltages of 80,100,and 120 kVp,and there were significant differences in all tube voltage conditions(P<0.05)except under the tube voltage condition of 120 kVp(P=0.190).In addition,after the application of the device for protection,the reduction rate of pelvic radiation dose under the tube voltages of 80 and 100 kVp was higher than that under the tube voltage of 120 kVp.Conclusion:The new 360-degree radiation protection and position fixation device can significantly reduce the cumulative radiation dose of pelvic organs during chest CT scan,and it holds promise for clinical application due to its characteristics of conve-nient wearing and fixed patient position.

Objective:To establish a preliminary performance validation protocol for the bioinformatics procedure of metagenomic next-generation sequencing (mNGS) in clinical laboratories.Methods:Three types of simulated datasets were designed and the CatⅠ dataset mainly consisted of pathogen reference genomes and human sequences. CatⅠA was a dataset composed of common pathogens mixed with human sequences and was used to evaluate the inclusiveness, accuracy, recall rates, precision, F1-Score, and other indicators of the mNGS bioinformatics procedure. CatⅠB was a dataset composed of closely related species of common pathogens mixed with human sequences, which was used to evaluate the discriminating ability of closely related species of bioinformatics procedure by calculating the detection rates and the relative abundance ratio of closely related species. The real data of 200 clinical samples was selected to construct CatⅡ and the simulated dataset consisted of colonized bacteria, experimental environment bacteria, reagent engineering bacteria, pathogen reference genomes, and human sequences, which was used to evaluate the sensitivity, specificity, and accuracy of bioinformatics pipeline for pathogens detection. The CatⅢ dataset was obtained from the negative bronchoalveolar lavage fluid BALF sequencing data mixed with 20 rare pathogens sequences in order to evaluate the positive detection rates and recall rates of rare pathogens in the bioinformatics analysis.Results:The analysis of the CatⅠA dataset showed that the positive consistency rate, inclusiveness, precision and accuracy of the bioinformatics peocedure under three sequence gradients were all greater than 99%, with a recall rate of 72.31% (95% CI 69.61%-75.01%) and a F1 Score of 82.00% (95% CI 79.77%-84.22%). In the CatⅠB dataset, the closely related species could be effectively detected at all sequence and proportion gradients, and the relative abundance ratio of closely related species was within 2 times of the design ratio except for the coronavirus, haemophilus, primate bocaparvovirus, human respiratory syncytial virus, and eimeria, indicating good ability to identify the closely related species. All the 24 species of pathogens included in CatⅡ dataset were effectively detected, with the sensitivity, specificity, and accuracy all greater than 90%. All rare pathogens were detected in the CatⅢ dataset, with a detection rate of 100%. Conclusions:With the simulated datasets, the performance validation scheme for the mNGS bioinformatics analysis was preliminary established and could evaluate the accuracy of sequence classification, the ability to identify the closely related species, and detection ability of common and rare pathogens, which may provide some references for the construction of mNGS process.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective To establish a performance verification scheme for the metagenomic next-generation sequencing(mNGS)DNA workflow.Methods Reference materials and clinical samples were used for conducting experiments.The mNGS detection results were evaluated in terms of limit of detection(LOD),repeatability,robustness,anti-interference ability,specificity and accuracy,as well as the patterns of library construction and the performance of sequencers.Results All species in the reference materials were stably detected,and the LOD of mNGS was 5.0E+02 CFU/mL(copies/mL).The repeatability was 100％and the within-batch(coefficient of variation)CV ranged from 8.53％to 38.73％.The linear correlation coefficient|r|＞0.9 was found between the input pathogenic microorganism concentration and the read count.Meanwhile,the experimental robustness was found to be good.The results of the anti-interference test showed that the higher concentration of human DNA inputted,the fewer pathogenic microorganism read counts detected by mNGS.Meanwhile,the read counts of related species presented a proportional relationship with the corresponding pathogenic microorganisms concentration inputted,which meant the validation of the cross-interference test had been passed.Furthermore,the detection result of D0 was negative.The accuracy of clinical samples testing was 90.9％(10/11).In addition,the library quality control results obtained by the automatic liquid handling workstation and manually operation were all acceptable.The performance of the three Illumina sequencers met or were better than the factory standards.Conclusion The clinical laboratory performance verification scheme for mNGS detection was established,which included the design for reference materials,comparison of different patterns for library construction,and performance evaluation of the sequencers.More importantly,the performance verification scheme can be used to evaluate and ensure the quality of mNGS DNA workflow detection process.

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major,but only half of patients can find compatible bone marrow or peripheral blood stem cells.Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells,and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major.OBJECTIVE:To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment of β-thalassemia major in children.METHODS:Forty-eight children with β-thalassemia major,including 28 males and 20 females,with a median age of 4 years old,were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020.All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling.Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin.A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.RESULTS AND CONCLUSION:(1)The median infused doses of total nucleated cells and CD34+cells were 8.17×107/kg and 2.40×105/kg,respectively in 48 children.The median follow-up time after cord blood transplantation was 98 months,and 44 cases were successfully engrafted.The median time to neutrophil and platelet engraftment was 28 and 31 days,respectively.Among them,37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation,7 cases were found to be stable mixed chimerism.(2)Among the 44 children with successful implantation,four patients developed acute graft-versus-host disease,and were scored as grade Ⅰ(n=2)and grade Ⅱ(n=2).All the affected organs were skin,and no chronic graft-versus-host disease occurred.(3)After umbilical cord blood transplantation,cytomegalovirus infection and activation occurred in 5 of the 48 cases,sepsis in 12 cases,invasive fungal disease in 3 cases,stomatitis in 21 cases,hemorrhagic cystitis in 8 cases,and hepatic vein occlusion in 1 case.(4)Among 48 children,47 patients survived;1 died of severe pneumonia combined with acute heart failure 28 days after transplantation;43 survived without disease;3 had primary implantation failure,and 1 had pancytopenia after transplantation.The 5-year probabilities of overall survival and disease-free survival were 98％and 89％,respectively.The cumulative incidence of transplant-related deaths at 1 year was 2.1％.(5)The above results indicate that human leukocyte antigen matched sibling fresh umbilical cord blood transplantation is effective in the treatment of β-thalassemia major in children with a low incidence of graft-versus-host disease.