Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases: A case report.

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Tissue-specific populations from amniotic fluid-derived mesenchymal stem cells manifest variant in vitro and in vivo properties.

Amniotic fluid derived mesenchymal stem cells (AFMSCs), shed along the fetal development, exhibit superior multipotency and immunomodulatory properties compared to MSCs derived from other somatic tissues (e.g., bone marrow and fat). However, AFMSCs display heterogeneity due to source ambiguity, making them an underutilized stem cells source for translational clinical trials. Consequently, there is an urgent need to identify a method to purify the AFMSCs for clinical use. We found that the AFMSCs can be categorized into three distinct groups: kidney-specific AFMSCs (AFMSCs-K), lung-specific AFMSCs (AFMSCs-L), and AFMSCs with an undefined tissue source (AFMSCs-X). This classification was based on tissue-specific gene expression pattern of single cell colony. Additionally, we observed that AFMSCs-X, a minority population within the AFMSCs, exhibited the highest multipotency, proliferation, resistance to senescence and immuno-modulation. Our results showed that AFMSCs-X significantly improved survival rates and reduced bacterial colony forming units (CFU) in cecal ligation and puncture (CLP)-induced septic mice. Therefore, our study introduces a novel classification method to enhance the consistency and efficacy of AFMSCs. These subpopulations, originating from different tissue source, may offer a valuable and innovative resource of cells for regenerative medicine purposes.

Hyperprogression after anti-programmed death-1 therapy in a patient with urothelial bladder carcinoma: A case report.

BACKGROUND: Immune checkpoint inhibitors, including programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) have recently been approved to treat locally advanced and metastatic urothelial carcinoma (UC). However, some patients experience rapid tumor progression rather than any clinical benefit from anti-PD-L1/PD-1 therapy. CASE SUMMARY: A 73-year-old woman with bladder UC showed the progression of multiple metastases after surgery and chemotherapy for over 12 mo. The patient could not tolerate further chemotherapy. Next-generation sequencing was performed, and the results indicated that the tumor mutational burden was 6.4 mutations/Mb. The patient received the anti-PD-L1 agent toripalimab combined with albumin-bound paclitaxel. Compared with the baseline staging before immunotherapy, the patient had a treatment failure time of < 2 mo, an increase in tumor burden of > 50%, and a > 2-fold increase in progression, indicating hyperprogression. CONCLUSION: Selecting patients most likely to respond to treatment with immunotherapeutic agents remains challenging. For older patients with advanced UC who have already exhausted multi-line chemotherapy options, immunotherapy should be used prudently if no effective biomarker is available. Further studies are required to clarify the causes and mechanisms of hyperprogression.

Haplotype-specific MAPK3 expression in 16p11.2 deletion contributes to variable neurodevelopment.

Recurrent proximal 16p11.2 deletion (16p11.2del) is a risk factor for diverse neurodevelopmental disorders with incomplete penetrance and variable expressivity. Although investigation with human induced pluripotent stem cell models has confirmed disruption of neuronal development in 16p11.2del neuronal cells, which genes are responsible for abnormal cellular phenotypes and what determines the penetrance of neurodevelopmental abnormalities are unknown. We performed haplotype phasing of the 16p11.2 region in a 16p11.2del neurodevelopmental disorders cohort and generated human induced pluripotent stem cells for two 16p11.2del families with distinct residual haplotypes and variable neurodevelopmental disorder phenotypes. Using transcriptomic profiles and cellular phenotypes of the human induced pluripotent stem cell-differentiated cortex neuronal cells, we revealed MAPK3 to be a contributor to dysfunction in multiple pathways related to early neuronal development, with altered soma and electrophysiological properties in mature neuronal cells. Notably, MAPK3 expression in 16p11.2del neuronal cells varied on the basis of a 132 kb 58 single nucleotide polymorphism (SNP) residual haplotype, with the version composed entirely of minor alleles associated with reduced MAPK3 expression. Ten SNPs on the residual haplotype were mapped to enhancers of MAPK3. We functionally validated six of these SNPs by luciferase assay, implicating them in the residual haplotype-specific differences in MAPK3 expression via cis-regulation. Finally, the analysis of three different cohorts of 16p11.2del subjects showed that this minor residual haplotype is associated with neurodevelopmental disorder phenotypes in 16p11.2del carriers.

PAK2 is essential for chromosome alignment in metaphase I oocytes.

As a highly conserved and ubiquitously expressed serine/threonine kinase, p21-activated kinase 2 (PAK2) participates in diverse biologic events. However, its roles in mouse oocyte meiotic maturation remain unclear. The present study revealed that mouse oocytes depleted of Pak2 were unable to completely progress through meiosis and that a majority were arrested at metaphase I. Pak2 depletion thus prompted MI arrest and induced meiotic chromosome alignment defects in mouse oocytes, in part due to a reduction in polo-like kinase (PLK1). We demonstrated that PAK2's interaction with PLK1 protected it from degradation by APC/CCdh1, and that it promoted meiotic progression and bipolar spindle formation. Our data collectively display critical functions for PAK2 in meiotic progression and chromosome alignment in mouse oocytes.

FOXO3a-dependent up-regulation of HSP90 alleviates cisplatin-induced apoptosis by activating FUNDC1-mediated mitophagy in hypoxic osteosarcoma cells.

Hypoxia-induced decrease in cisplatin (CDDP) sensitivity in human osteosarcoma (OS) is a significant obstacle to effective chemotherapy. Recently, mitophagy has been shown to be associated with CDDP sensitivity. However, whether it regulates hypoxia-induced decreases in CDDP sensitivity in OS and the underlying mechanisms remain unknown. In this study, we found that hypoxia activated mitophagy and suppressed mitophagy with specific inhibitors, mitochondrial division inhibitor-1 (Mdivi-1) or lysosome inhibitor chloroquine (CQ), which inhibited CDDP-induced apoptosis in hypoxic U-2OS and MG-63 cells. In addition, hypoxia upregulated the phosphorylation level of FUN14 domain-containing protein 1 (FUNDC1), whereas the activation of mitophagy and decreased CDDP sensitivity were inhibited by transfection with FUNDC1 small interfering RNA (siRNA). Hypoxia treatment also led to the up-regulation of heat shock protein 90 (HSP90), whereas HSP90 siRNA inhibited FUNDC1-mediated activation of mitophagy and decreased CDDP sensitivity. Furthermore, activation of Unc-51 like autophagy activating kinase 1 (Ulk1) was found in U-2OS and MG-63 cells after induction of hypoxia. Overexpression of Ulk1 prevented the inhibitory effect of HSP90 siRNA on the activation of FUNDC1 and mitophagy and decreased CDDP sensitivity in hypoxic U-2OS and MG-63 cells. Finally, hypoxia induced the activation of forkhead box transcription factor 3a (FOXO3a), whereas FOXO3a siRNA inhibited hypoxia-induced HSP90 up-regulation, Ulk1 activation, and FUNDC1-mediated activation of mitophagy, and decreased CDDP sensitivity in U-2OS and MG-63 cells. Using a chromatin immunoprecipitation (ChIP) assay, we confirmed that FOXO3a binds to the HSP90 promoter region. In conclusion, our findings suggest that hypoxia alleviates CDDP-induced apoptosis by activating mitophagy through the FOXO3a/HSP90/Ulk1/FUNDC1 signaling pathway in OS cells.

Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for ß-Thalassemia.

Reactivation of γ-globin expression is a promising therapeutic approach for ß-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of ß-thalassemia: Natural HPFH mutations -113A > G, -114C > T, -117G>A, -175T > C, -195C > G, and -198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from ß-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for ß-thalassemia.

A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia.

Background: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. Methods: A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. Results: In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1-1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55-1), as revealed by receiver operating characteristic analysis. Conclusions: Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.

Effects of aerobic exercise and resistance exercise on physical indexes and cardiovascular risk factors in obese and overweight school-age children: A systematic review and meta-analysis.

BACKGROUND: Obesity is a serious social and public health problem in the world, especially in children and adolescents. For school-age children with obesity, this stage is in the transition from childhood to adolescence, and both physical, psychological, and external environments will be full of challenges. Studies have showed that school-age children are the largest proportion of people who continue to be obese in adulthood. Physical exercise is considered as an effective way to control weight. Therefore, we focus on this point to study which factors will be improved to reduce childhood obesity. OBJECTIVE: To assess the effects of aerobic and resistance exercise on physical indexes, such as body mass index (BMI) and body fat percentage, and cardiovascular risk factors such as VO2peak, triglycerides (TG) and low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), insulin and insulin resistance in school-age children who are overweight or obese. METHOD: PubMed, SPORTDiscus, Medline, Cochrane-Library, Scopus, Ovid and Web of Science were searched to locate studies published between 2000 and 2021 in obese and overweight school-age children between 6-12 years old. The articles are all randomized controlled trials (RCTs) and in English. Data were synthesized using a random-effect or a fixed-effect model to analyze the effects of aerobic and resistance exercise on six elements in in school-age children with overweight or obese. The primary outcome measures were set for BMI. RESULTS: A total of 13 RCTs (504 participants) were identified. Analysis of the between-group showed that aerobic and resistance exercise were effective in improving BMI (MD = -0.66; p < 0.00001), body fat percentage (MD = -1.29; p = 0.02), TG (std.MD = -1.14; p = 0.005), LDL (std.MD = -1.38; p = 0.003), TC (std.MD = -0.77; p = 0.002), VO2peak (std.MD = 1.25; p = 0.001). However, aerobic and resistance exercise were not significant in improving HDL (std.MD = 0.13; p = 0.27). CONCLUSIONS: Aerobic exercise and resistance exercise are associated with improvement in BMI, body fat percentage, VO2peak, TG, LDL, TC, while not in HDL in school-age children with obesity or overweight. Insulin and insulin resistance were not able to be analyzed in our review. However, there are only two articles related to resistance exercise in children with obesity and overweight at school age, which is far less than the number of 12 articles about aerobic exercise, so we cannot compare the effects of the two types of exercises.

Generation of a homozygous ZBTB7A knockout human induced pluripotent stem line by CRISPR/Cas9 editing.

ZBTB7A plays important roles in several biological processes, including silencing of the fetal γ-globin genes, hematopoiesis, primed-to-naive transition, etc. Meanwhile, it is also associated with Oncogenic transformation and tumor progression. However, the mechanism of ZBTB7A function is not fully understood yet. Here, we generated a homozygous ZBTB7A knockout human induced pluripotent stem cell (iPSC) line, GZHMCi007-A by the CRISPR/Cas9-mediated homology-dependent DNA repair method. The iPSCs of ZBTB7A-/- established by us is a powerful tool for related research.

Design consideration of an x-ray imaging crystal spectrometer for China Fusion Engineering Test Reactor.

The x-ray imaging crystal spectrometer (XICS) is proposed as the principal method of diagnostics for plasma ion temperature and rotation for the China Fusion Engineering Test Reactor (CFETR) for its simplicity in implementation and no reliance on neutral beams. For D-T experiments with the electron temperature as high as 35-40 keV at the core region, highly charged high-Z ions can serve as the diagnostic ions for the XICS. For the CFETR, Xe44+, Xe51+, and W64+ are selected as the impurity ions. Appropriate crystal parameters are selected, as well as the preliminary layout for the spectrometer. We estimated the general performance of the spectrometer, including the emissivity of the impurities, the spatial resolution of the x-ray detector, and the expected count rate of line emissions. For the application in the fusion reactor environment, the effect of neutron irradiation on the crystal is briefly discussed.

[Effect of electrothermal acupuncture on moderate to severe cancer pain with yin-cold stagnation: a randomized controlled trial].

OBJECTIVE: To observe the effectiveness and safety of electrothermal acupuncture therapy for patients of moderate to severe cancer pain with yin-cold stagnation. METHODS: A total of 60 patients of moderate to severe cancer pain with yin-cold stagnation were randomized into an observation group and a control group, 30 cases in each one. In the control group, opioid painkillers (oxycodone hydrochloride prolonged-release tablet or morphine sulfate sustained-release tablet) were taken. On the basis of the control group, electrothermal acupuncture was applied at Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Hegu (LI 4), Sanyinjiao (SP 6) in the observation group, 30 min each treatment, once a day for 5 days. Before and after treatment, the scores of pain numerical rating scale (NRS) and Karnofsky performance scale (KPS) were observed in the two groups. The pain remission rate, reduction of opioid painkillers and safety were compared. RESULTS: The variation of NRS scores in the observation group were larger than the control group 3, 5 days into treatment (P<0.01, P<0.05). The variation of KPS score in the observation group was larger than the control group after treatment (P<0.05). The pain remission rate was 100.0% (30/30) in the observation group, higher than 86.7% (26/30) in the control group (P<0.05). The reduction of opioid painkillers in the observation group was larger than the control group (P<0.01). There was no adverse reaction during the treatment in the two groups. CONCLUSION: On the basis of the conventional western medication for analgesia, electrothermal acupuncture could relieve pain, reduce the dose of opioid painkillers and improve the quality of life in patients of moderate to severe cancer pain with yin-cold stagnation, has a better safety.

Comparison of contrast-enhanced ultrasound targeted biopsies versus standard systematic biopsies for prostate cancer correction in different PSA value groups in rural China.

OBJECTIVE: To investigate prostate cancer detection rate of different biopsy protocols in different PSA value groups in rural China. METHODS: A total of 186 patients underwent contrast-enhanced ultrasound (CEUS) in order to determine the puncture target prior to biopsy were enrolled in this retrospective study. All patients underwent 12-core SB combined with CEUS-TB. The biopsy results of different biopsy protocols were compared in patients with stratification by PSA value. RESULTS: Among the 186 patients underwent prostate biopsy, the histopathologic results revealed prostate cancer (PCa) in 117 cases (62.9%) and benign lesions in 69 cases (37.1%). The PCa detection rate between 8-core SB and 12-core SB showed no significant difference in PSA 4-10 ng/ml group, while the 12-core SB was significantly higher than CEUS-TB (44.9% versus 32.7%, P = 0.01). In PSA 10-20 ng/ml group, the significant difference was not seen between SB and CEUS-TB (50.0% versus 45.7%, P = 0.15). As for PSA greater than 20 ng/ml group, the PCa detection rate by SB was higher than CEUS-TB, but showed no statistically significance (79.1% versus 76.9%, P = 0.15). In the overall patients, the biopsy core positive rate of CEUS-TB was significantly higher than SB (97% versus 55.5% and 28.5%, P = 0.0001). CONCLUSION: The flexible use of SB combined with CEUS-TB can reduce the number of biopsy cores in higher PSA groups. It has clinical importance in the detection of PCa in different PSA value groups in rural China.

Generation of induced pluripotent stem cell GZLSL-i001-A derived from urine-derived cells of Hemophilia A patient with Inv22 mutation.

Hemophilia A (HA), is a X-linked recessive congenital bleeding disorder, caused by deficiency of the coagulation factorVIII (FVIII) which is encoded by coagulation factor 8 (F8). HA affects 1 of every 5,000 males worldwide. The intron 22 inversion (Inv22) mutation of F8 causes about 45% of severeHA cases.Here, we generated induced pluripotent stem cells (iPSCs) from a HA patient with Inv22 mutation by electroporation of urine-derived cells (UCs) with episomal plasmids under feeder-free, virus-free, serum-free condition and without oncogene c-MYC. This iPSCs line could facilitate future applications of human iPSCs by provide a valuable cell model.

L-Arginine Supplementation Improves Vascular Endothelial Dysfunction Induced by High-Fat Diet in Rats Exposed to Hypoxia.

INTRODUCTION: Our previous study showed that high-fat diet inhibited the increase in nitric oxide and endothelial nitric oxide synthase expression in the aortic endothelium of rats exposed to hypoxia, and hypoxia plus a high-fat diet led to earlier and more severe vascular endothelial dysfunction (VED) than hypoxia alone. The purpose of the present study was to investigate the effects of L-arginine on high-fat diet-induced VED of rats in hypoxia. METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups and treated with hypoxia (H group), hypoxia plus high-fat diet (H+HFD group), hypoxia plus L-arginine (H+L-Arg group), and hypoxia plus high-fat diet and L-arginine (H+HFD+L-Arg group) for 1 wk. Hypoxia was simulated in a hypobaric chamber with an altitude of 5000 m. Aortic morphology and endothelium-dependent vasorelaxation were used to assess VED. RESULTS: High-fat diet impaired vascular remodeling and reduced endothelium-dependent vasodilator response to acetylcholine in rats exposed to hypoxia, secondary to dysregulation of the nitric oxide pathway. L-arginine supplementation significantly increased plasma nitrates and nitrites and endothelial nitric oxide synthase mRNA levels and improved ultrastructural changes in aortic endothelium and endothelium-dependent vasodilator response. CONCLUSIONS: L-arginine prevents aortic ultrastructural changes and reverses VED induced by high-fat diet in rats exposed to hypoxia, which may have implications for VED induced by high-fat diet in high altitude dwellers.

Increased stability and intracellular antioxidant activity of chlorogenic acid depend on its molecular interaction with wheat gluten hydrolysate.

Gastrointestinal stability and cell entry efficiency affect the biological accessibility of chlorogenic acid (CGA). Here, wheat gluten hydrolysate (WGH) was proven to improve the stability of CGA during simulated gastrointestinal digestion, promote the intestinal epithelial cell entry efficiency of CGA, and increase its intracellular antioxidant activity. The interaction between WGH and CGA was studied by fluorescence quenching and molecular dynamics simulations. The thermodynamic parameters and molecular dynamics simulation analysis showed that the interaction between WGH and CGA was dependent on hydrogen bonding and hydrophobic and electrostatic interactions. Analyses of the binding sites of WGH showed that Arg12, Arg49, Lys54, and Pro74-Gln89 had strong interactions with CGA molecules. This interaction between CGA and WGH was related to both electrostatic interactions and their respective concentrations. Taken together, the stability, intestinal epithelial cell entry, and antioxidant activity of CGA can be increased by its molecular interactions with WGH.

A meta-analysis of the safety and efficacy of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type-5 inhibitors for pulmonary arterial hypertension.

Bosentan is an effective drug for the treatment of pulmonary arterial hypertension (PAH). The aim of the present meta-analysis was to examine the evidence concerning the efficacy and safety of bosentan therapy combined with prostacyclin analogues or phosphodiesterase type 5 (PDE-5) inhibitors for treating PAH. Eligible published studies were collected from Embase, PubMed, The Cochrane Library and the www.clinicaltrials.gov website. Heterogeneity was assessed using the Cochran Q-statistic test. Results were presented as risk ratios or mean differences with 95% confidence intervals (CI). A total of five studies, comprising 310 patients were included for analysis. No significant improvements in six-minute walk distance (6MWD; mean difference, 16.43 m), clinical worsening (risk ratio, 0.54) and the World Health Organization functional classification (class I: risk ratio, 1.17; class II: risk ratio, 1.18) were observed in patients treated with bosentan in combination with prostacyclin analogues or PDE-5 inhibitors. However, a significant reduction in the mean pulmonary artery pressure (mPAP; 95% CI: -17.06, -6.83; P<0.0001) following bosentan combination therapy was observed. Comparisons of adverse event rates in the bosentan combination therapy (55.6%) and monotherapy (51.8%) suggested that there is no reduction in adverse events (risk ratio, 1.10). The results indicated that bosentan combined with prostacyclin analogues or PDE-5 inhibitors may not improve 6MWD, cardiac function, clinical worsening and adverse events. However, bosentan combined with prostacyclin analogues or PDE-5 inhibitor therapy was able to significantly reduce mPAP compared with the effect of bosentan monotherapy.

Efficient gene correction of an aberrant splice site in ß-thalassaemia iPSCs by CRISPR/Cas9 and single-strand oligodeoxynucleotides.

ß-thalassaemia is a prevalent hereditary haematological disease caused by mutations in the human haemoglobin ß (HBB) gene. Among them, the HBB IVS2-654 (C > T) mutation, which is in the intron, creates an aberrant splicing site. Bone marrow transplantation for curing ß-thalassaemia is limited due to the lack of matched donors. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), as a widely used tool for gene editing, is able to target specific sequence and create double-strand break (DSB), which can be combined with the single-stranded oligodeoxynucleotide (ssODN) to correct mutations. In this study, according to two different strategies, the HBB IVS2-654 mutation was seamlessly corrected in iPSCs by CRISPR/Cas9 system and ssODN. To reduce the occurrence of secondary cleavage, a more efficient strategy was adopted. The corrected iPSCs kept pluripotency and genome stability. Moreover, they could differentiate normally. Through CRISPR/Cas9 system and ssODN, our study provides improved strategies for gene correction of ß-Thalassaemia, and the expression of the HBB gene can be restored, which can be used for gene therapy in the future.

Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with ß-Thalassemia Major: A Meta-Analysis.

BACKGROUND: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. METHODS: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. RESULTS: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. CONCLUSION: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

The value of oral contrast ultrasonography in the diagnosis of gastric cancer in elderly patients.

BACKGROUND: This study aims to investigate the value of oral contrast ultrasonography (OCUS) in the diagnosis of gastric cancer in elderly patients. METHODS: OCUS data obtained from patients ≥ 60 years old were retrospectively analyzed and compared with gastroscopy results. RESULTS: Among the 12,716 subjects examined by OCUS, 5021 subjects were ≥ 60 years old, which accounted for 39.48% (5021/12,716). Gastritis, gastric polyp, benign ulcer, and gastric cancer were detected by OCUS in 1099 patients. Among them, 196 patients underwent gastroscopy. Furthermore, ulcerative lesions were detected in 32 patients by OCUS and in 51 patients by gastroscopy, and the coincidence rate was 62.74%. Among these patients, gastric cancer was diagnosed in 18 patients by OCUS with a detection rate of 1.64% (18/1099) and detected in 19 patients by gastroscopy with a diagnostic coincidence rate of 94.73% (18/19). Furthermore, benign ulcer was detected in 14 patients by OCUS and in 32 patients by gastroscopy, and the diagnostic coincidence rate was 43.75% (14/32). CONCLUSION: OCUS helps to timely detect senile gastric cancer and can be used as a suitable technique for the detection of gastric diseases.