Objective To investigate the relationship between the changes in vasopressin(VP)level and disease severity and prognosis in patients with septic shock(SS).Methods A total of 96 patients with SS in the hospital from December 2021 to December 2022 were selected as the study group,and 95 healthy volun-teers in the hospital during the same period were selected as the control group.The plasma VP levels of the two groups were compared,and their correlation with multiple organ dysfunction syndrome(MODS)score,a-cute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,serum C-reactive protein(CRP),and procalcitonin(PCT)levels were analyzed.The study group received shock treatment,and was divided into a good prognosis group and a poor prognosis group based on the prognosis after 28 days of hospitalization.The clinical data of the two groups were compared.Multivariate Logistic regression analysis was used to analyze the factors affecting poor prognosis.A new prediction scheme and a conventional prediction scheme were con-structed,and the predictive efficacy of different prediction schemes was evaluated using area under the curve(AUC),net reclassification index and comprehensive discrimination improvement index.Results Compared with the control group,the plasma VP level in the study group was significantly decreased,and MODS score,APACHE Ⅱ score,the levels of serum CRP and PCT were significantly increased,with statistical significance(P＜0.05).Pearson correlation analysis showed that plasma VP level was negatively correlated with MODS score,APACHE Ⅱ score,serum CRP and PCT level(r=-0.426,-0.519,-0.483,-0.395,P＜0.05).The proportion of diabetes mellitus,acute respiratory distress syndrome(ARDS),acute kidney injury(AKI),MODS score,APACHE Ⅱ score,serum CRP and PCT levels in the poor prognosis group were higher than those in the good prognosis group,while the plasma VP level was lower than that in the good prognosis group,with statistical significance(P＜0.05).Logistic regression analysis showed that concurrent ARDS,concurrent AKI,plasma VP,MODS score,APACHE Ⅱ score,serum CRP and PCT were all influential factors for poor prognosis of SS patients(P＜0.05).The AUC of plasma VP predicting poor prognosis of SS patients was 0.752,and the AUC of the new prediction scheme predicting poor prognosis of SS patients was greater than that of the conventional prediction scheme predicting poor prognosis of SS patients(P＜0.05).Conclu-sion Plasma VP level decrease in SS patients and closely relate to the severity of the condition.Based on the results of Logistic regression analysis,the new predictive model is established,which has certain predictive value for poor prognosis.

OBJECTIVE: To explore the genotype-phenotype correlation of a Chinese pedigree affected with Lowe syndrome. METHODS: Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of his pedigree. RESULTS: The proband, a 3-year-and-5-month-old male, presented with multiple anomalies including congenital cataract, glaucoma, brain dysplasia, renal dysfunction and cognitive impairment. WES revealed that he has harbored a novel hemizygous missense variant of the OCRL gene, namely NM_000276.3: c.1255T>C (p.Trp419Arg) (GRCh37/hg19), which was derived from his unaffected mother. The same variant was not found in his elder brother who was healthy. The variant was predicted to be pathogenic according to ACMG/AMP guideline. Compared with previously reported cases of Lowe syndrome, our patient has displayed rare features including corpus callosum dysplasia, reduction of white matter, cerebral hypoplasia, laryngomalacia, sebaceous cyst, recurrent eczema, cryptorchidism, hypoglycemia and irritability. CONCLUSION Above finding has expanded the mutational spectrum of the OCRL gene, enriched clinical features of Lowe syndrome, and enabled genetic counseling for this pedigree.
Aged ; China ; Genetic Association Studies ; Humans ; Infant ; Male ; Mutation ; Oculocerebrorenal Syndrome ; Pedigree ; Phosphoric Monoester Hydrolases/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genotype-phenotype correlation of a case with GM1-gangliosidosis caused by compound heterogenic variants in GLB1. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Trio-based whole-exome sequencing (WES) was performed for the family and suspected mutation was verified by Sanger sequencing. RESULTS: The proband, a 2-year-3-month old Chinese girl, presented with psychomotor deterioration, absent speech, intellectual disabilities and behavior problem. Trio-based WES has identified compound heterozygosity for 2 variants in the GLB1 gene: NM_000404.2:c.1343A>T, p.Asp448Val and c.1064A>C, p.Gln355Pro (GRCh37/hg19),which was inherited from the mother and father, respectively. Homozygous or compound heterozygous pathogenic variants in GLB1, encoding β-galactosidase, are responsible for GM1-gangliosidosis,an autosomal recessive lysosomal storage disorder characterized by variable degrees of neurodegeneration and skeletal abnormalities. The p.Asp448Val variant has been classified as pathogenic for GM1 gangliosidosis in medical literatures for the reason that functional studies demonstrated that expression of the p.Asp448Val variant in COS-1 cells resulted in no detectable β-galactosidase activity compared to wild type GLB1. The p.Gln355Pro variant has not been reported in literatures or database. The variant is highly conserved residue (PM1), and was not found in either the Genome Aggregation Database or the 1000 Genomes Project (PM2) and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3). Next, the β-galactosidase activity of the patient's peripheral blood leukocytes was determined by fluorescent method. The result was 0.0 nmol/mg. It showed that the p.Gln355Pro variant also resulted in loss of β-galactosidase activity, thus the variant was classified into clinical pathogenic variant. CONCLUSION Our study expands the mutational spectrum of the GLB1 gene and provides genetic counseling for the family.
Asians/genetics* ; China ; Female ; G(M1) Ganglioside ; Gangliosidosis, GM1/genetics* ; Humans ; Mutation ; beta-Galactosidase/genetics*

OBJECTIVE: To explore the genotype-phenotype correlation of a case with Sifrim-Hitz-Weiss syndrome (SIHIWES) caused by a novel CHD4 gene variant. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Whole-exome sequencing (WES) was carried out for the patient.Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 2-year-old Chinese girl, presented with global developmental delay, intellectual disability, distinctive facial features and multiple congenital anomalies. Her prenatal manifestations included increased nuchal thickness, cranial and facial anomalies, and decreased fetal movement. WES has identified a novel variant in the CHD4 gene, namely NM_001273:c.2989C>G (p.Leu997Val) (GRCh37/hg19).Comparison of her phenotype with previously reported SIHIWES cases suggested that our patient's prenatal presentations were unreported before, with novel features including funduscopic anomaly, facial dysmorphisms such as asymmetrical ears, drooping eyelid, long philtrum and downturned mouth. CONCLUSION Above findings have expanded the mutational spectrum of the CHD4 gene and revealed novel phenotypes in Chinese patients with SIHIWES.
Child, Preschool ; China ; Congenital Abnormalities/genetics* ; Female ; Genetic Association Studies ; Genetic Testing ; Humans ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/genetics* ; Phenotype ; Pregnancy ; Syndrome ; Whole Exome Sequencing

Objective To investigate the effect of propofol on human renal tubule epithelial cell (HK-2 cells) fibrosis induced by ATP depletion/recovery and the role of transforming growth factor β activated kinase 1 (TAK1) in it.Methods HK-2 cells were seeded in 96-well plates,and randomly divided into 4 groups (n =36 each) using a random number table:control group (group C),ATP depletion/recovery group (group D/R),propofol group (group P),and TAK1 over-expression group (group T).HK-2 cells were exposed to antimycin A for 1 h and then returned to normal culture medium to establish the model of ATP depletion/recovery-induced injury.At 1 h before ATP depletion,the cells were incubated for 1 h in the DMEM liquid culture medium containing propofol with the final concentration of 20 μmol/L in group P,and the cells were incubated for 1 h in the DMEM liquid culture medium containing propofol with the final concentration of 20 μmol/L and TAK1 with the titer of 2× 107 TU/ml in group T,and the other treatments were similar to those previously described in group D/R.At 12 h after ATP recovery,the cell viability was evaluated by methyl thiazolyl tetrazolium assay,and cell apoptosis was detected using TUNEL and scored.The expression of TAK1 was detected using Western blot at 12,24 and 48 h after ATP recovery.The expression of α-smooth muscle actin (αSMA),fibronectin (FN),and collagen protein 1 (COL1) was measured at 48 h after ATP recovery.Results Compared with group C,the cell viability was significantly decreased,the apoptosis score was increased,and the expression of TAK1,COL1,αSMA and FN was up-regulated after ATP recovery in D/R,P and T groups (P＜0.05).Compared with group D/R,the cell viability was significantly increased,the apoptosis score was decreased,and the expression of TAK1,COL1,αSMA and FN was down-regulated after ATP recovery in P and T groups (P＜0.05).Compared with group P,the cell viability was significantly decreased,the apoptosis score was increased,and the expression of TAK1,COL1,αSMA and FN was up-regulated after ATP recovery in group T (P＜ 0.05).Conclusion Propofol can reduce HK-2 cell fibrosis induced by ATP depletion/recovery,and the mechanism may be related to down-regulation of TAK1 expression.

Objective: Numerous studies have shown that bone marrow-derived mesenchymal stem cells (MSCs) enhance neurological recovery after cerebral ischemia. However, the mechanisms are still not clear. The present study aimed to investigate the beneficial effects of MSCs on global cerebral ischemia induced by cardiac arrest (CA) and the underlying mechanisms. Methods: Rats subjected to asphyxial CA were injected intravenously with MSCs (5×106 ) at 2 hours after resuscitation. Whole brain histopathologic damage scores (HDS) were assessed by histopathology at 3 and 7 days after resuscitation. The distribution of donor MSCs in the brain was evaluated. The expression of tumor necrosis factor-α-induced protein 6 (TSG-6) and pro-inflammatory cytokines in cerebral cortex was assayed. After intravenous infusion of TSG-6 siRNA-MSCs, HDS and pro-inflammatory cytokines were reevaluated at 7 days after resuscitation. Results: Intravenously administered MSCs significantly reduced whole brain HDS after global cerebral ischemia. Immunofluorescence microscopy revealed that donor MSCs were primarily found in cerebral cortex and expressed TSG-6. MSCs treatment significantly increased the expression of TSG-6 and reduced the expression of pro-inflammatory cytokines in cerebral cortex. In addition, intravenous infusion of TSG-6 siRNA-MSCs failed to attenuate brain inflammation. Conclusion: Systemically administered MSCs reduced inflammatory damage to brain in rats with global cerebral ischemia via secretion of TSG-6.
Heart Arrest ; Mesenchymal Stromal Cells

Objective To evaluate the effect of rhubarb on intestinal mucosal damage in septic rats by comparing with ulinastatin.Methods A total of 84 healthy Sprague-Dawley rats (half male,half female),aged 3 months,weighing 200-330 g,were randomly divided into 5 groups according to the random number table:control group (group C,n =6),sham operation group (group S,n =6),sepsis group (group Sep),rhubarb group (group R,n=24) and ulinastatin group (group U,n=24).Sepsis was induced by cecum ligation and puncture.In group R,rhubarb 1.2 g/100 g was dissolved in normal saline at room temperature,3 and 4 h later the filtrate about 2-3 ml was obtained and injected through a gastric tube into stomach once every 12 h,and 72 h later sepsis was induced.In group U,ulinastatin 50 000 U/kg (in 2 ml of normal saline) was injected once every 24 h,and 72 h later sepsis was induced.In Sep,R and U groups,at 6,12,24 and 48 h after ligation (T1 4),blood samples were collected from the orbital venous plexus for determination of plasma diamine oxidase (DAO) activity.Results The activity of plasma DAO was significantly higher at T1-4 in Sep,R and U groups than in C and S groups.The activity of plasma DAO was significantly lower at T3,4 in R and U groups than in Sep group.There was no statistical difference in the plasma DAO activity between R group and U group.Conclusion Rhubarb can reduce intestinal mucosal damage in septic rats,which is similar to that of ulinastatin.

OBJECTIVETo observe the clinical efficacy and side effects of brentuximab vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and refractory Hodgkin lymphoma (HL) after failure with BV alone.

METHODSFrom March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg, iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course, and all patients received about 3-8 courses of chemotherapy, with an median of 4 courses. Clinical efficacy and adverse events were assessed and observed by radiographic examination and serological detection.

RESULTSAmong 6 patients, the overall response rate was 100% with 2 complete remission and 4 partial remission. The main adverse events were grade I (2 patients) and IV (2 patients) bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I (1 patient) increase of transaminase and myocardial enzyme and grade I (1 patient) mouth ulcers.

CONCLUSIONThe combination of BV and CH in the treatment of relapsed and refractory HL after failure with BV alone was high effective and the toxicities were well tolerable.

Objective To evaluate the accuracy of vasopressin (VP) secretion in the late phase of septic shock for predicting patient outcomes and further investigate its relationship with the prognosis of septic shock.Methods Fifty-five patients presented at late phase of septic shock,who were admitted to the intensive care unit of our hospital,were enrolled.Their VP secretion was measured.The method for measurement was as follows:3％ sodium chloride solution 600 ml was infused over 2 h,serum concentrations of VP and sodium were measured before and after infusion,the difference in VP before and after infusion (△VP) and in Na before and after infusion (△Na) was calculated,and △VP/△Na was used to reflect VP secretion.The patients were divided into either abnormal secretion of VP group (△ VP/△ Na ≤ 0.5 ng/mmol) or normal secretion of VP group (△VP/△Na＞0.5 ng/mmol) according to △VP/△Na ratio.Immediately before testing VP secretion,venous blood samples were collected for determination of serum lactic acid and C-reactive protein concentrations.The consumption of vasoactive drugs at the moment of enrollment and 28-day fatality rate were recorded.Results There were 30 cases in abnormal group (54％) and 25 cases in normal group (46％).Compared with normal group,the serum lactic acid,C-reactive protein concentrations and consumption of dopamine or norepinephrine were significantly increased,and the 28-day fatality rate was increased (67％ vs 40％) in abnormal group.ROC curve analysis showed that when △VP/△Na 0.5 ng/mmol was used as the criteria for determining prognosis,the sensitivity was 66.7％,specificity was 64.0％,and the area under the ROC curve was 0.828.Conclusion VP secretion in the late phase of septic shock may affect patient prognosis.

Objective To investigate the prognostic value of decreased vasopressin (VP)modulation in the late-phase of septic shock. Methods A prospective study was conducted. Fifty-five septic shock patients hospitalized in intensive care unit (ICU)of the First Hospital of Hebei Medical University from January 2012 to February 2014 were enrolled. All patients received 3% hypertonic saline solution infusion. Serum concentrations of sodium and VP were measured before and after hypertonic saline solution infusion. Patients with ratio of difference in sodium and VP before and after infusion of 3%hypertonic saline (△VP/△Na)≤0.5 pg/mmol were defined as non-responders,and who>0.5 pg/mmol were defined as responders. The levels of lactic acid,C-reactive protein (CRP),and vasoactive drug〔dopamine(DA)and norepinephrine(NE)〕usage between the two groups were compared. The 28-day mortality,live time in the dead,and ICU day in survivors were analyzed between the two groups. The receiver operating characteristic curve (ROC curve)was drawn to assess prognostic value of VP. Results There were 30 cases (54.5%) in non-responsive group,and 25 (45.5%)in responsive group. There were no significant differences in the age,acute physiology and chronic health evaluationⅡ (APACHEⅡ)score,central venous pressure (CVP),blood pressure, plasma albumin level,sodium level before and after hypertonic saline solution infusion between the two groups. The baseline level of VP in the non-responsive group was markedly lower than that of the responsive group (ng/L:10.66± 1.57 vs. 17.13 ±5.12,t=6.091,P<0.001). After hypertonic saline solution infusion,the VP level was also significantly decreased compared with that in the responsive group(ng/L:11.65±1.74 vs. 22.50±5.31,t=9.758,P<0.001). The non-responders showed higher lactic acid (mmol/L:3.04±0.55 vs. 2.28±0.38,t=-5.881,P<0.001) and CRP (mg/L:117.9±23.0 vs. 94.9±17.0,t=-4.143,P<0.001),and received larger dosage of vasoactive drugs〔DA(μg·kg-1·min-1):14.8±3.9 vs. 8.9±1.6,t=-5.725,P<0.001;NE(μg·kg-1·min-1):0.96±0.42 vs. 0.40± 0.09,t=-5.625,P<0.001〕for maintaining blood pressure compared with those in responders. The non-responsive group showed higher 28-day mortality(66.7%vs. 40.0%,χ2=3.911,P=0.048)and longer ICU day(days:9.9±2.3 vs. 6.7±1.7,t=-4.044,P<0.001),but the live time in the dead showed no difference between non-responsive group and responsive group(days:5.8±1.9 vs. 6.1±2.3,t=0.384,P=0.704). ROC curve showed that the area under ROC curve(AUC)forΔVP/ΔNa predicting the outcome was 0.828,and theΔVP/ΔNa threshold value of 0.5 pg/mmol had the sensitivity of 66.7%and specificity of 64.0%for prediction of the outcome(95%confidence interval:0.722-0.934). Conclusion Osmotic pressure-regulated VP secretion was impaired and decreased in the late-phase of septic shock, and made the sense in prognosis.