Clinical manifestations of adult hereditary spherocytosis with novel SPTB gene mutations and hyperjaundice: A case report.

BACKGROUND: The aim of the present study was to enhance understanding of the diagnosis and treatment of atypical hereditary spherocytosis (HS), and to broaden the diagnostic thoughts of physicians for patients with jaundice. CASE SUMMARY: A 28-year-old male presented with jaundice, bile duct stone, and splenomegaly, but without anemia. Other causes of jaundice were excluded, and gene sequencing revealed a novel heterozygous variant of c.1801C>T (p.Q601X) in exon 14 of the SPTB (NM_01355436) gene on chromosome 14 (chr14: 65260580) in the patient's blood; the biological parents and child of the patient did not have similar variants. A splenectomy was performed on the patient and his bilirubin levels returned to normal after surgery. Thus, a novel gene variant causing HS was identified. This variant may result in the truncation of ß-hemoglobin in the erythrocyte membrane, leading to loss of normal function, jaundice, and hemolytic anemia. The clinical manifestations of the patient were hyperjaundice and an absence of typical hemolysis during the course of the disease, which caused challenges for diagnosis by the clinicians. CONCLUSION: Following a definitive diagnosis, genetic testing and response to treatment identified a gene variant site for a novel hemolytic anemia.

An initial study on the comparison of diagnostic performance of 18F-FDG PET/MR and 18F-FDG PET/CT for thoracic staging of non-small cell lung cancer: Focus on pleural invasion.

OBJECTIVE: To compare the diagnostic performance of 18F-FDG PET/MR and PET/CT preliminarily for the thoracic staging of non-small cell lung cancer (NSCLC) with a special focus on pleural invasion evaluation. METHODS: 52 patients with pathologically confirmed NSCLC were included and followed for another year. Whole-body 18F-FDG PET/CT and subsequent thoracic PET/MR were performed for initial thoracic staging. Thoracic (simultaneous) PET/MR acquired PET images and MRI sequences including T2 weighted imaging, with and without fat saturation, T1 weighted imaging, and diffusion weighted imaging (DWI). Two radiologists independently assessed the thoracic T, N staging and pleural involvement. The McNemar Chi-square test was used to compare the differences between PET/CT and PET/MR in the criteria. The area under the receiver-operating-characteristic curves (AUC) was calculated. RESULTS: Compared to PET/CT, PET/MR exhibited higher sensitivity, specificity in the detection of pleural invasion; 82 % vs. 64% (p = 0.625), 98 % vs. 95% (p = 1.000), PET/MR to PET/CT respectively. The receiver-operating-characteristic analysis results of PET/CT vs PET/MR for the pleural invasion were as follow: AUCPET/CT = 0.79, AUCPET/MR = 0.90, p = 0.21. Both T staging results and N staging results were approximately identical in PET/CT and PET/MR. Differences between PET/CT and PET/MR in T staging, N staging as well as pleural invasion accuracy were not statistically significant (p > 0.05, each). CONCLUSION: PET/MR and PET/CT demonstrated equivalent performance about the evaluation of preoperative thoracic staging of NSCLC patients. PET/MR may have greater potential in pleural invasion evaluation for NSCLC, especially for solid nodules, crucial to clinical decision-making, though our results did not demonstrate statistical significance.

Efficacy and Treatment Strategies in Advanced Cancers with Liver Metastasis Receiving Atezolizumab Therapy.

BACKGROUND: Atezolizumab has been used to treat patients with liver metastasis (LM). However, whether atezolizumab is superior to standard of care therapy in an all-comer or selective population with LM is still uncertain. METHODS: A pooled analysis based on 10 randomized controlled trials was conducted to evaluate the clinical benefit of atezolizumab versus standard therapy in patients stratified by liver metastatic status, followed by biomarker-based individual analyses of the non-small cell lung cancer (NSCLC) cohort (OAK and POPLAR studies) and urothelial cancer cohort (IMvigor210 study). RESULTS: The pooled analysis demonstrated an overall survival (OS) improvement using atezolizumab treatment versus standard therapy across cancer types and treatment lines regardless of liver metastatic status. However, the efficacy of atezolizumab in patients with LM from the second-line setting was limited, based on the individual analysis of NSCLC cohorts (P = 0.053). PD-L1 strong expression emerged as a predominant biomarker (P = 0.015) to screen atezolizumab-advantageous patients with LM. Notably, the combination of PD-L1 and LM improved the predictive power for atezolizumab therapy in both NSCLC and urothelial cancer cohorts. Exploratory translational analysis revealed that strong expression of PD-L1 might have reversed the non-inflamed immune phenotype of liver metastasis, thus sensitizing these patients to immunotherapy. CONCLUSION: Our study demonstrated a preferable efficacy of atezolizumab in patients with LM as first-line therapy over standard of care therapy, while sensitive patients should be selected in second-line settings. PD-L1 was demonstrated as the most effective biomarker for screening atezolizumab-advantageous patients with LM.

The cleft palate candidate gene BAG6 supports FoxO1 acetylation to promote FasL-mediated apoptosis during palate fusion.

BACKGROUND: Cleft palate is a common craniofacial defect, which occurs when the palate fails to fuse during development. During fusion, the palatal shelves migrate towards the embryonic midline to form a seam. Apoptotic elimination of medial edge epithelium (MEE) cells along this seam is required for the completion of palate fusion. METHODS: Whole exome sequencing (WES) of six Chinese cleft palate families was applied to identify novel cleft palate-associated gene variants. Palatal fusion and immunofluorescence studies were performed in a murine palatal shelf organ culture model. Gene and protein expression were analyzed by qPCR and immunoblotting in murine MEE cells during seam formation in vivo. Mechanistic immunoprecipitation studies were performed in murine MEE cells in vitro. RESULTS: WES identified Bcl-2 associated anthanogene 6 (BAG6) as a novel cleft palate-associated gene. In murine MEE cells, we discovered upregulation of Bag6 and the transcription factor forkhead box protein O1 (FoxO1) during seam formation in vivo. Using a palatal shelf organ culture model, we demonstrate that nuclear-localized Bag6 enhances MEE cell apoptosis by promoting p300's acetylation of FoxO1, thereby promoting transcription of the pro-apoptotic Fas ligand (FasL). Subsequent gain- and loss-of-function studies in the organ culture model demonstrated that FasL is required for Bag6/acFoxO1-mediated activation of pro-apoptotic Bax/caspase-3 signaling, MEE apoptosis, and palate fusion. Palatal shelf contact was shown to enhance Bag6 nuclear localization and upregulate nuclear acFoxO1 in MEE cells. CONCLUSIONS: These findings demonstrate that nuclear-localized Bag6 and p300 co-operatively enhance FoxO1 acetylation to promote FasL-mediated MEE apoptosis during palate fusion.

WITHDRAWN: Paeoniflorin attenuates LPS-induced inflammation in nucleus pulposus cells via Nrf-2/HO-1/HMGB1/NF-κB pathway.

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Students' Interest in Surgery Affects Laparoscopic Practicing Performance.

BACKGROUND AND OBJECTIVE: Earlier exposure to laparoscopic techniques is thought to be beneficial for medical students. Reports have demonstrated that practice improves performance in laparoscopies. In this study, we intended to evaluate whether medical students' interest in surgery is affected by the amount of practice and the performance on a laparoscopic simulator. METHODS: A laparoscopic simulation curriculum was introduced at Taipei Medical University, Wan-Fang Medical Center. Study participants included 36 sixth-year and 14 seventh-year students who were divided according to whether they had indicated an interest (group A) or not (group B) in surgery. The students had twice-a-week practice sessions for 2 weeks. They underwent baseline measurement (BM) before training and posttraining measurement (PTM). Self-guided practice on the simulator was allowed. The learning outcomes were assessed comparing the BM and PTM scores by using the interquartile range (IQR) test. We also tested the correlation between total score and number of self-guided practice sessions. RESULTS: All study participants showed improvement. No differences were observed between BM and PTM scores and between 6th- and 7th-year medical students. Significant differences were found in PTM scores between groups A and B (P < .001). Analysis of variance with a post hoc test for different groups revealed that the PTMs were significantly higher for both the 6th- and 7th-year medical students in group A than for those in group B (P < .001). Total performance scores were improved with a higher number of self-guided practice sessions. Linear regression analysis demonstrated a significant correlation between the number of self-guided practice sessions and total performance score (P < .001). CONCLUSION: Those clerks and interns interested in surgery who had more sessions for self-guided practice, displayed more improvement than those not interested in surgery did. Improvement in performance correlated highly with trainees' number of self-guided practice sessions.

A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti-hepatitis C target.

G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the high genetic variability of this ribovirus; we further show using various methods that such consensus sequences can fold into unimolecular G4 RNA structures, both in vitro and under physiological conditions. Furthermore, we provide direct evidences that small molecules specifically targeting G4 can stabilize this structure to reduce RNA replication and inhibit protein translation of intracellular hepatitis C. Ultimately, the stabilization of G4 RNA in the genome of hepatitis C represents a promising new strategy for anti-hepatitis C drug development.

Synthesis of N-vinylindoles through copper catalyzed cyclization reaction of N-(2-alkynylphenyl)imine.

A copper(II)-catalyzed cyclization reaction of N-(2-alkynylphenyl)imine was developed. This strategy provided an effective procedure for the synthesis of substituted N-vinylindoles in moderate to good yields.

[Clinical effects of low-stretch ventilation on acute respiratory distress syndrome].

OBJECTIVE: To investigate the effectiveness of low-stretch as compared with low-tidal-volume strategy in the treatment of acute respiratory distress syndrome (ARDS). METHODS: Eighty-five cases of ARDS patients were randomly divided into low-stretch group (42 cases) and low-tidal-volume group (43 cases). The former group of patient received pressure assist control mode with not higher than 35 cm H(2)O (1 cm H(2)O=0.098 kPa) of peak pressure or pressure support mode ventilation with not higher than 30 cm H(2)O of Pplateau, while in low-tidal-volume group tidal volume of no more than 6 ml/kg of predicted body weight was given. The mortality rate within 28 days, the incidence of hypercapnia, the duration of using sedatives and neuromuscular blockade agents, the time of ventilation and the length of intensive care unit (ICU) stay were compared between two groups. According to the monitored expiratory tidal volume (V(T)e), the low-stretch group was divided into low-tidal-volume subgroup (V(T)e < or =6 ml/kg, 11 cases) and non-low-tidal-volume subgroup (V(T)e >6 ml/kg, 31 cases). The mortality within 28 days and the incidence of hypercapnia were compared between two subgroups. RESULTS: There was no significant difference in the 28-day mortality rate between two groups (34.0% vs. 37.0%, P>0.05), but patients of low-stretch group had lower incidence of hypercapnia than low-tidal-volume group (10.6% vs. 40.7%, P<0.05), and also the duration of using sedatives [(4.5+/-1.2) days vs. (8.7+/-2.3) days] and neuromuscular blockade agents [(8.4+/-2.1) days vs. (10.7+/-1.2) days], and the length of ventilation and ICU stay [(10.2+/-2.2) days vs. (13.7+/-3.1) days, all P<0.05] were less. Low tidal volume occurred in 26.2% of low-stretch group, and the low-tidal-volume subgroup had higher 28-day mortality rate (40.8%) and incidence of hypercapnia (65.7%) than non-low-tidal-volume subgroup (13.2% and 8.6%, both P<0.05). CONCLUSION: Compared with low-tidal-volume strategy, low-stretch strategy can reduce the incidence of hypercapnia, the length of ventilation and ICU stay for ARDS patients, but have similar mortality rate. When low-stretch strategy is exercised, an inappropriate low tidal volume may be associated with poor outcome of ARDS.

[Identification and molecular study on vibrio cholerae in sea products].

OBJECTIVE: To investigate the serologic type, phage-biotype and toxic factor of Vibrio cholerae isolated from different sea products, analyze the relation between the Vibrio cholerae in sea products and cholera epidemiology, and provide references for forecasting cholera epidemic situation and drawing out a preventing plan. METHOD: The biotype of strains isolated was analyzed by using type and phage-biotype serological methods. The toxic gene was detected by PCR. RESULTS: The constituent ratio of V. cholerae O139, Ogawa and Inaba were, respectively, 48.44%, 20.31% and 31.25% in 64 strains of V. cholerae. The result of phage-biotype showed that the 26 strains of V. cholerae O1 were all non-epidemic strains. The result of toxic gene detecting showed that positive rate of V. cholerae O139 was higher than those of Ogawa and Inaba. CONCLUSION: The positive rate of toxic gene in V. cholerae O139 was high and the V. cholerae O139 was mainly in turtle, breed aquatics water and crustacean, so these sea products were the important sectors in cholera prevention and control.

[The first confirmed human case of avian influenza A (H5N1) in mainland, China].

OBJECTIVE: To ascertain the causation of a family cluster involving two undefined pneumonia cases, a 12-year-old girl and her brother, reported October, 2005 in Xiangtan county, Hunan province. METHODS: Information on epidemiology and clinical manifestation of the cases was collected from interviewing the keyman and referring to related medical records. The environment exposure of the cases to their households and the timeline of the illness were reproduced, using this information. Medical check-up was undergone among the close contacts of the cases and on sick/dead poultry. Throat swab of the cases were collected and tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were then inoculated into special pathogen free (SPF) embryonated hens' eggs. Serum of the cases including acute and convalescent phases were also collected and tested by microneutralization and haemagglutination-inhibition (HI) assays to detect H5-specific antibodies. RESULTS: Both the girl and her brother developed fever 2 and 4 days after sudden deaths of chickens being raised in the same house. Both of them had developed pneumonia and the girl died from acute respiratory distress syndrome (ARDS) complicated with multi-organ failure. The boy survived and subsequently discharged from hospital. An eighth-day serum from the girl tested H5 antibody negative, while 4-fold and greater increased in antibody titers were detected in serum from the boy using microneutralization and HI assays in sequential acute and convalescent sera. Of 192 cases, only one doctor who cared for the girl during hospitalization had upper respiratory symptoms but tested negative for H5N1 by microneutralization assay. CONCLUSION: The boy was the first confirmed human case of avian influenza A (H5N1) in the mainland of China and his sister was diagnosed clinically. The most probable explanation of these two cases was that the transmission of H5N1 virus from infected poultry within the same household environment. No evidence of human-to-human transmission was noted in the family cluster.

[Study on a fatal pregnant woman died from by avian influenza (H5N1)].

OBJECTIVE: To ascertain the causation of a pregnant woman with undefined pneumonia reported from the People's Hospital of Tongling city in Anhui province on November 2005. METHODS: Epidemiological and clinical information of the case was collected from the keypersons close to the case and referring to the medical record. A medical observation was carried out on the close contacts of the case and sick or dead poultry. Tracheal aspirates being collected were tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were inoculated into special pathogen free (SPF) embryonated hens' eggs. RESULTS: The pregnant woman was found to have been contacted with the sick/dead poultry directly on the 4th day before onset of illness. All the 122 close contacts were healthy after a 10-day medical observation. The major clinical features of the case were viral pneumonia with rapidly developed leukopenia and lymphopenia. The progress to acute respiratory distress syndrome and multiple organ dysfunction syndromes was found at clinical presentation. HA and NA gene of A/H5N1 virus were positive. The 8 gene fragments of A/Anhui/1/2005 (H5N1) isolated from the tracheal aspirates had not carried genes from a human virus through reassortment, and the receptor-binding site of the hemagglutinin was polybasic cleavage site. CONCLUSION: This was the first documented case of H5N1 infection in pregnant woman. The immunotolerant state of pregnancy might have predisposed to the fatal outcome of the patient.

Analysis of dermatomycoses in Lanzhou district of northwestern China.

The skin mycoses, perticularly dermatophytoses, in Lanzhou district, Northwestern China, was investigated during July 2002-June 2003. The specimens from patients suspected of having dermatomycoses were examined microscopically in KOH preparations and cultured on Sabouraud dextrose agar (SDA). Among 1443 suspected cases, 594 were KOH positive and 221 cultures of fungi were isolated. The most frequently isolated fungi were Trichophyton rubrum (43.9%) Trichophyton mentagrophytes (29.4%) and Candida species (14.0%). The frequency of tinea pedis, onychomycosis and tinea manuum were 38.7, 27.8 and 13.5%, respectively. In Lanzhou district, tinea pedis is the most commonly seen dermatophytoses, and T. rubrum is the most frequent etiologic agent.