Objective:To evaluate the effect of difference of fluid intake and excretion on the prognosis of elderly patients with septic shock during hospitalization in ICU, and to provide evidence for clinical assessment of the condition, prognosis prediction, and optimization of fluid resuscitation strategies during hospitalization.Methods:A retrospective cohort study was conducted, involving elderly septic shock patients admitted to the ICU of Zhoupu Hospital affiliated to Shanghai Health College from January 2018 to June 2024. Data on general characteristics, clinical parameters at 6 h and 24 h after ICU admission, and cumulative difference of fluid intake and excretion during ICU stay were collected. Patients were divided into survival group and death group based on whether they survived during hospitalization. Differences in study variables between groups were analyzed. Logistic regression analysis was performed on the independent risk factors of the mortality rate during hospitalization. Receiver operating characteristic (ROC) was plotted to evaluate the prognostic value of difference of fluid intake and excretion in elderly patients with septic shock during hospitalization in ICU.Results:A total of 159 elderly septic shock patients were included (108 males, 51 females), with an in-hospital mortality rate of 66.66% (106 deaths vs. 53 survivors). Compared with the survival group, the difference of total fluid intake and excretion during hospitalization in ICU in the death group was significantly lower [2 441.00 (228.50, 5 101.50) mL vs. 6 215.50 (3 755.00, 9 874.75) mL, P<0.001]. Multivariate logistic regression analysis showed that SOFA score ( OR=1.359, 95% CI: 1.135-1.626, P=0.001) and the difference of total fluid intake and excretion during hospitalization in ICU ( OR=1.174, 95% CI: 1.067-1.291, P=0.001) were independent risk factors for predicting prognosis during hospitalization. ROC analysis revealed that the cumulative difference of fluid intake and excretion achieved an AUC of 0.756 (95% CI: 0.674-0.838, P<0.001), with a sensitivity of 61.8% and specificity of 82.4% at a cutoff value of ≥5 396.5 mL. In addition, AUC of the total fluid intake and excretion difference and SOFA score during hospitalization in ICU was 0.885 (95% CI: 0.825-0.944, P<0.001). Conclusions:A higher cumulative difference of fluid intake and excretion during ICU hospitalization is associated with increased mortality in elderly septic shock patients. A positive difference of fluid intake and excretion may serve as a clinical indicator for predicting prognosis of elderly patients with septic shock.

OBJECTIVE: To explore the clinical characteristics and genetic factors in four patients with Disorder of sex development (DSD). METHODS: Four patients who visited Tianjin Medical University General Hospital between January 2023 and January 2024, presenting with short stature, abnormal external genitalia, or infertility as their chief complaints, were selected as the study subjects. Clinical data were collected, and peripheral or umbilical cord blood samples were obtained for karyotyping analysis and low-depth whole-genome sequencing (CNV-seq). Quantitative fluorescence PCR (QF-PCR) was used to detect the sex-determining region Y (SRY) gene and azoospermia factor (AZF) on the Y chromosome, while fluorescence in situ hybridization (FISH) was employed to determine the location of the SRY gene. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variants. The study procedure and protocol were approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethics No.: IRB2024-WZ-006). RESULTS: Case 1 had a karyotype of 45,X[22]/46,XY[8], with CNV-seq indicating a mosaic deletion of 7.44 Mb (copy number = 0.2) at Yp11.31-p11.2, a mosaic deletion of 5.32 Mb (copy number = 0.3) at Yq11.1-q11.221, and a deletion of 10.26 Mb (copy number = 0) at Yq11.221-q11.23. Y chromosome microdeletion analysis showed SRY and AZFa (+), AZFb+c (-). Case 2 had a karyotype of 45,X[12]/46,X,del(X)(q26.3)[18], with CNV-seq indicating a mosaic deletion of 132.62 Mb (copy number = 1.4) at Xp22.33-q26.3 and a deletion of 19.62 Mb (copy number = 1) at Xq26.3-q28. Case 3 had a karyotype of 46,XX, with CNV-seq showing two copies of the X chromosome and no Y chromosome. Y chromosome microdeletion analysis showed SRY (+) and AZFa+b+c (-), and FISH confirmed a translocation of the SRY gene to the terminal end of the short arm of the X chromosome. Case 4 had a karyotype of 46,XY, with CNV-seq showing one copy each of the X and Y chromosomes. Y chromosome microdeletion analysis showed SRY(+) and AZFa+b+c (+), and WES revealed a c.1103del variant in the AR gene (maternal origin), which was classified as a pathogenic variant based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+PP1+PM2_Supporting). CONCLUSION The combined application of multiple detection techniques such as chromosomal karyotyping analysis, CNV-seq, QF-PCR, and WES can identify the genetic etiology of DSD patients, providing a basis for clinical consultation and treatment plan formulation.
Humans ; Male ; Female ; Chromosomes, Human, Y/genetics* ; Disorders of Sex Development/genetics* ; Sex-Determining Region Y Protein/genetics* ; Karyotyping ; In Situ Hybridization, Fluorescence ; Exome Sequencing ; Adult ; Child

Objective:To explore the clinical characteristics and genetic factors in four patients with Disorder of sex development (DSD).Methods:Four patients who visited Tianjin Medical University General Hospital between January 2023 and January 2024, presenting with short stature, abnormal external genitalia, or infertility as their chief complaints, were selected as the study subjects. Clinical data were collected, and peripheral or umbilical cord blood samples were obtained for karyotyping analysis and low-depth whole-genome sequencing (CNV-seq). Quantitative fluorescence PCR (QF-PCR) was used to detect the sex-determining region Y ( SRY) gene and azoospermia factor ( AZF) on the Y chromosome, while fluorescence in situ hybridization (FISH) was employed to determine the location of the SRY gene. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variants. The study procedure and protocol were approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethics No.: IRB2024-WZ-006). Results:Case 1 had a karyotype of 45, X[22]/46, XY[8], with CNV-seq indicating a mosaic deletion of 7.44 Mb (copy number = 0.2) at Yp11.31-p11.2, a mosaic deletion of 5.32 Mb (copy number = 0.3) at Yq11.1-q11.221, and a deletion of 10.26 Mb (copy number = 0) at Yq11.221-q11.23. Y chromosome microdeletion analysis showed SRY and AZFa (+ ), AZFb+ c (-). Case 2 had a karyotype of 45, X[12]/46, X, del(X)(q26.3)[18], with CNV-seq indicating a mosaic deletion of 132.62 Mb (copy number = 1.4) at Xp22.33-q26.3 and a deletion of 19.62 Mb (copy number = 1) at Xq26.3-q28. Case 3 had a karyotype of 46, XX, with CNV-seq showing two copies of the X chromosome and no Y chromosome. Y chromosome microdeletion analysis showed SRY (+ ) and AZFa+ b+ c (-), and FISH confirmed a translocation of the SRY gene to the terminal end of the short arm of the X chromosome. Case 4 had a karyotype of 46, XY, with CNV-seq showing one copy each of the X and Y chromosomes. Y chromosome microdeletion analysis showed SRY(+ ) and AZFa+ b+ c (+ ), and WES revealed a c. 1103del variant in the AR gene (maternal origin), which was classified as a pathogenic variant based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+ PP1+ PM2_Supporting). Conclusion:The combined application of multiple detection techniques such as chromosomal karyotyping analysis, CNV-seq, QF-PCR, and WES can identify the genetic etiology of DSD patients, providing a basis for clinical consultation and treatment plan formulation.

Objective:To explore the clinical characteristics and genetic factors in four patients with Disorder of sex development (DSD).Methods:Four patients who visited Tianjin Medical University General Hospital between January 2023 and January 2024, presenting with short stature, abnormal external genitalia, or infertility as their chief complaints, were selected as the study subjects. Clinical data were collected, and peripheral or umbilical cord blood samples were obtained for karyotyping analysis and low-depth whole-genome sequencing (CNV-seq). Quantitative fluorescence PCR (QF-PCR) was used to detect the sex-determining region Y ( SRY) gene and azoospermia factor ( AZF) on the Y chromosome, while fluorescence in situ hybridization (FISH) was employed to determine the location of the SRY gene. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variants. The study procedure and protocol were approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethics No.: IRB2024-WZ-006). Results:Case 1 had a karyotype of 45, X[22]/46, XY[8], with CNV-seq indicating a mosaic deletion of 7.44 Mb (copy number = 0.2) at Yp11.31-p11.2, a mosaic deletion of 5.32 Mb (copy number = 0.3) at Yq11.1-q11.221, and a deletion of 10.26 Mb (copy number = 0) at Yq11.221-q11.23. Y chromosome microdeletion analysis showed SRY and AZFa (+ ), AZFb+ c (-). Case 2 had a karyotype of 45, X[12]/46, X, del(X)(q26.3)[18], with CNV-seq indicating a mosaic deletion of 132.62 Mb (copy number = 1.4) at Xp22.33-q26.3 and a deletion of 19.62 Mb (copy number = 1) at Xq26.3-q28. Case 3 had a karyotype of 46, XX, with CNV-seq showing two copies of the X chromosome and no Y chromosome. Y chromosome microdeletion analysis showed SRY (+ ) and AZFa+ b+ c (-), and FISH confirmed a translocation of the SRY gene to the terminal end of the short arm of the X chromosome. Case 4 had a karyotype of 46, XY, with CNV-seq showing one copy each of the X and Y chromosomes. Y chromosome microdeletion analysis showed SRY(+ ) and AZFa+ b+ c (+ ), and WES revealed a c. 1103del variant in the AR gene (maternal origin), which was classified as a pathogenic variant based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+ PP1+ PM2_Supporting). Conclusion:The combined application of multiple detection techniques such as chromosomal karyotyping analysis, CNV-seq, QF-PCR, and WES can identify the genetic etiology of DSD patients, providing a basis for clinical consultation and treatment plan formulation.

Objective:To test the feasibility, efficacy and safety of percutaneous patent foramen ovale(PFO) closure utilizing the Pansy biodegradable occluder(PBO) at 1-, 3-, 6-, 12-, 24-, and 36-month follow-up.Methods:In this single-center prospective clinical study, we enrolled 15 patients with PFO eligible for closure, all treated with the PBO, with device sizes ranging 24-34 mm. All clinical data were recorded in a 36-month follow-up period. Patients were summoned to the hospital in the 1, 3, 6, 12, 24, and 36 months after closure for transthoracic echocardiography(TTE), or transesophageal echocardiography(TEE), contrast transcranial doppler(cTCD) or contrast transthoracic echocardiography(cTTE), and a routine fasting blood sample.Results:The mean age was 27-68(44.0±16.4) years old. Indications for closure were cryptogenic stroke in 6 patients and migraine in 9 patients. Procedures were technically successful in 100%(15/15), in which course TTE showed that the position and shape of occluders were satisfactory. Small residual shunt was found by TTE in 2 patients with ASA in 1 month and 6 months after closure, respectively. 1 patient with cryptogenic stroke had another recurrent stroke 8 months after closure. At 12-month follow-up, 11 cases were closure. At 36-month follow-up, 13 cases were closure. 12 patients without atrial septal aneurysm(ASA) were closure. 1 patients with ASA was complete closure. No device-related complications occurred during the follow-up.Conclusion:PBO has good biocompatibility and suitable degradation time. A high technical success rate and closure rate can be achieved in those patients without ASA. Percutaneous closure of PFO using PBO is feasible, effective, and safe.

Objective:To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16).Methods:A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus.Results:The couple′s first pregnancy had resulted in a miscarriage at 27 + 5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30 + 5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c. 3172C>T (p.R1058W) and paternal c. 1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+ PM2_supporting+ PP3+ PP4), whilst the c. 1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+ PM2_supporting+ PP4). Conclusion:The c. 3172C>T (p.R1058W) and c. 1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.

Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

Objective:To investigate the prognostic value of albumin (ALB), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT) in patients with acute liver failure (ALF) in hyperacute phase of sepsis which provided the basis for clinical evaluation and prognostic judgment and corresponding treatment options.Methods:A multicenter retrospective cohort study was conducted. Patients with ALF in hyperacute phase of sepsis admitted to Zhoupu Hospital Affiliated to Shanghai Health College, Shanghai Pudong New Area People's Hospital, and Shanghai Oriental Hospital from January 2019 to February 2024 were enrolled. General data such as gender and age of the patients were collected. Lactate dehydrogenase (LDH), liver function indexes [total bilirubin (TBIL), direct bilirubin (DBIL), AST, ALT, AST/ALT, ALB, total protein (TP), globulin (GLB), ALB/GLB ratio (A/G), blood amine, γ-glutamyl transpeptidase (γ-GT)], platelet count (PLT), creatinine, activated partial thromboplastin time (APTT), severity of illness scores [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), sequential organ failure assessment (SOFA)], serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), arterial blood lactic acid (Lac) within 24 hours after admission, and whether to use mechanical ventilation, whether to use vasoactive drugs, whether to use artificial liver treatment and prognosis during hospitalization also were collected. The differences of clinical data between patients with different prognosis were compared. The variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to determine the independent risk factors for death of patients with ALF in hyperacute phase of sepsis during hospitalization. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of ALB and AST/ALT for death of patients with ALF in hyperacute phase of sepsis during hospitalization.Results:A total of 73 patients with ALF in hyperacute phase of sepsis were included, with 22 survived and 51 died during hospitalization and the mortality of 69.86%. Compared with the survival group, the patients in the death group had lower ALB, γ-GT within 24 hours after admission and proportion of artificial liver treatment, and higher AST/ALT, SOFA score, LDH and proportion of use of vasoactive drugs. The differences were statistically significant. Multivariate Logistic regression analysis showed that ALB and AST/ALT were the independent risk factors for death in patients with ALF in hyperacute phase of sepsis during hospitalization [ALB: odds ratio ( OR) = 0.856, 95% confidence interval (95% CI) was 0.736-0.996, P = 0.044; AST/ALT: OR = 2.018, 95% CI was 1.137-3.580, P = 0.016]. ROC curve analysis showed that the area under the curve (AUC) of ALB for predicting in-hospital death in patients with ALF in hyperacute phase of sepsis was 0.760 (95% CI was 0.637-0.884, P < 0.001). When ALB ≤ 29.05 g/L, the sensitivity was 68.2%, and the specificity was 76.5%. The AUC of AST/ALT for predicting in-hospital death in patients with ALF in hyperacute phase of sepsis was 0.764 (95% CI was 0.639-0.888, P < 0.001). When AST/ALT ≥ 1.26, the sensitivity was 59.1%, and the specificity was 90.2%. Conclusions:The lower the ALB level, and the higher the AST/ALT within 24 hours after admission, the worse the prognosis of patients with ALF in hyperacute phase of sepsis. ALB and AST/ALT can be used as clinical indicators to evaluate the severity and prognosis of patients with ALF in hyperacute phase of sepsis.

Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.