The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Aim To investigate the effect of marine herbal seahorse on chronic unpredictable mild stress ( CUMS ) -induced depression-like model in zebrafish. Methods Adult zebrafish were divided into control, Stress,Stress + low dose (Stress +0.044% SH) and Stress + high dose (Stress +0. 22% SH) seahorse intervention groups, and depression-like behavior was identified by novel tank test (NTT), cortisol, interleukin ( IL )-6 and interferon (IFN )-γ levels were detected by ELISA. The levels of dopamine (DA) ,norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyin-doleacetic acid (5-HIAA) were determined by high performance liquid chromatography. The mRNA expression levels of tryptophan hydroxylase(TPH)-2 and 5-HT2A receptor were measured by real-time quantitative PCR. Results Compared with the control group, the Stress group showed significantly longer latency to reach the top in NTT, significantly reduced number of transfers to the top region and top residence time, significantly increased levels of cortisol and IL-6, IFN-γ protein, significantly reduced levels of DA and 5-HT in brain as well as increased metabolism rate of 5-HT, while 5-HT2A mRNA expression was up-regulated and TPH2 mRNA expression was down-regulated. In contrast, low-dose seahorse intervention effectively reduced anxiety, decreased cortisol and IL-6 and IFN-γ concentrations, increased monoamine neurotransmitter levels and reversed dysregulation of the 5-HT ergic system in CUMS zebrafish. Conclusion Seahorse may exert an-tidepressant effects through anti-inflammation and mod¬ulation of monoamine neurotransmitter levels.

OBJECTIVE: To explore the carrier rate, genotype and phenotype of α-thalassemia fusion gene in Huadu district of Guangzhou, Guangdong province of China, and provide data reference for the prevention and control of thalassemia. METHODS: A total of 10 769 samples who were screened for thalassemia in Maternal and Child Health Hospital of Huadu District from July 2019 to November 2020 were analyzed retrospectively. Blood cell analysis and hemoglobin (Hb) electrophoresis were performed. Thalassemia genes were analyzed by gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB). RESULTS: A total of 9 cases with α-thalassemia fusion gene were detected in 10 769 samples (0.08%). There were 7 cases with fusion gene heterozygote, 1 case with compound of α-thalassemia fusion gene and Hb G-Honolulu, 1 case with compound of α-thalassemia fusion gene and Hb QS. The MCV results of 4 samples of blood cell analysis were within the reference range, the Hb A2 value of 1 case was decreased, and there were no other abnormalities found. CONCLUSION The α-thalassemia fusion gene is common in Huadu district of Guangzhou, and heterozygotes are more common, and current screening methods easily lead to misdiagnosis.
Humans ; alpha-Thalassemia/genetics* ; Retrospective Studies ; beta-Thalassemia/genetics* ; Genotype ; Phenotype ; Heterozygote ; China ; Mutation

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Adolescent ; Adult ; Beijing/epidemiology* ; Contact Tracing ; Female ; Humans ; Male ; Prevalence ; Tuberculosis/transmission* ; Universities ; Young Adult

OBJECTIVE: To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). METHODS: This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. RESULTS: Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307-0.567)]. A longer duration of CM therapy (6-12 months, 12-18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I-IIIA (HR=0.50, 95% CI: 0.37-0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33-0.71), DFS was even longer among CM treatment group patients. CONCLUSIONS Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398).

OBJECTIVE To study the effect of Cistanches phenylethanol glycosides (CPhGs) on acute lung injury in rats and the possible mechanism of action. METHODS Sixty SD rats were randomly divided into six groups: Normal control group, model group (lipopolysasccharide (LPS) 3 mg·kg-1], dexamethasone (Dex) positive control group (model+ Dex 2 mg·kg-1), model + CPhGs 125, 250 and 500 mg·kg-1 with 10 rats in each group. Each dose group of CPhGs was ig administered every day for 30 d, and the other three groups were ig administered with the same volume of distilled water for 30 d. The mode+Dex 2 mg·kg-1 group was ig given Dex 2 mg·kg-11 h before modeling. The rat model of acute lung injury was established after the rats in the other groups were intubated by the breath tube. Three hours after modeling, the rats were sacrificed by blood sampling from the abdominal aorta. The percentage of neutrophils in the whole blood, the activity of serum superoxide dismutase (SOD), glutathione (GSH) activity and the contents of malondialdehyde (MDA) and nitric oxide (NO) were detected. The contents of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in alveolar lavage fluid were detected. The wet/dry mass ratio (W/D) of the middle lobe of the right lung was calculated and the histopathological changes of the posterior lobe of the right lung were observed by HE staining. RESULTS Compared with normal control group, the percentage of neutrophils in the whole blood, W/D in the middle lobe of the right lung, the contents of MDA and NO in the serum were increased (P<0.05), but SOD, GSH, TNF-α and IL-6 were decreased in the model group (P<0.05). Compared with the model group, the percentage of neutrophils in the whole blood and W/D in right middle lobe of the right lung in the group of model+CPhGs 500 mg·kg-1 was decreased (P<0.05), but the contents of TNF-α and IL-6 in alveolar lavage fluid of rats decreased significantly, and histopathological observation showed that inflammation was alleviated to varying degrees. The activities of SOD and GSH in rat serum of the model + CPhGs 500 mg·kg-1 group were increased significantly (P<0.05), while the contents of MDA and NO were decreased significantly (P<0.05). CONCLUSION CPhGs have a protective effect against acute lung injury induced by LPS in rats, and its mechanism may be related to its antioxidant effect, alleviation of pulmonary edema and reduction of the release of inflammatory factors.

BackgroundAs a major complication after orthotopic liver transplantation (OLT), the occurrence of acute kidney injury (AKI) is frequently defined by serum creatinine (Cr); however, the accuracy of commonly used blood urea nitrogen (BUN), uric acid (UA), and β-microglobulin (β-MG) remains to be explored. This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation.

MethodsPatients who underwent OLT in three centers between July 2003 and December 2013 were enrolled. The postoperative AKI group was diagnosed by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and classified by stage. Measurement data were analyzed using the t-test or Wilcoxon rank-sum test; enumerated data were analyzed using the Chi-square test or Fisher's exact test. Diagnostic reliability and predictive accuracy were evaluated using receiver operating characteristic (ROC) curve analysis.

ResultsThis study excluded 976 cases and analyzed 697 patients (578 men and 119 women); the post-OLT AKI incidence was 0.409. Compared with the no-AKI group, the AKI group showed very significant differences in Model for End-stage Liver Disease score (14.74 ± 9.91 vs. 11.07 ± 9.54, Z = 5.404; P < 0.001), hepatic encephalopathy (45 [15.8%] vs. 30 [7.3%], χ = 12.699; P < 0.001), hemofiltration (28 [9.8%] vs. 0 [0.0%], χ = 42.171; P < 0.001), and 28-day mortality (23 [8.1%] vs. 9 [2.2%], χ = 13.323; P <0.001). Moreover, mean values of Cr, BUN, UA, and β-MG in the AKI group differed significantly at postoperative days 1, 3, and 7 (all P < 0.001). ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 (sensitivity 80.1%, specificity 75.7%, cutoff value 88.23 μmol/L), 0.916 for Stage 2 (sensitivity 87.6%, specificity 82.6%, cutoff value 99.9 μmol/L), and 0.972 for Stage 3 (sensitivity 94.1%, specificity 88.2%, cutoff value 122.90 μmol/L).

ConclusionThe sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.

Acute Kidney Injury ; blood ; Adult ; Blood Urea Nitrogen ; Creatinine ; blood ; Female ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Retrospective Studies ; Uric Acid ; blood ; beta 2-Microglobulin ; blood

Objective To observe the anti-relapse and anti-graft versus host disease (GVHD) effects and side effects of ruxolitinib on patients who have relapsed leukemia after allo-hematopoietic stem cell transplantation (HSCT).Methods The clinical data of four patients sufferring from relapsed leukemia were collected and analyzed retrospectively.Three cases had a positive gene and 1 case had a extramedullary recurrence.All of them had serious GVHD involving multiparts,as the result of attenuating immunosuppressant aggressively.One case had central nervous system leukemia before allo-HSCT.Those patients were treated with ruxolitinib,according to the degree of GVHD,the treatment strategy and curative effect of GVHD,and the residual condition of original leukemia.Then,the degree of GVHD,the residual condition of original leukemia and the side effects of ruxolitinib were revaluated once a month after taking ruxolitinib.Results One case achieved completer remission (CR) and there partial remission (PR) in consideration of GVHD.Up to date,2 cases had no relapse in any level and 2 cases replased according to any of the results related to bone marrow aspiration.Conclusion Ruxolitinib is effective in patients with GVHD after allo-HSCT and doesn't influence GVL effect or increase the risk of relapse at the same time.Ruxolitinib doesn't have obvious side effects when treating GVHD.