Novel Variants in the FIG4 Gene Associated With Chinese Sporadic Amyotrophic Lateral Sclerosis With Slow Progression

Background@#and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. @*Methods@#All 23 exons of FIG4 were sequenced using targeted next-generation sequencing.An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. @*Results@#No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. @*Conclusions@#Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.

Preparation and in vitro release of quercetin nanocrystals self-stabilized Pickering emulsion / 中国中药杂志

A new quercetin nanocrystals self-stabilized Pickering emulsion(QT-NSSPE) was prepared by high-pressure homogenization combined with probe ultrasonic method. The influences of oil fraction, quercetin(QT) concentration, and pH of water phase on the formation of QT-NSSPE were investigated. On this basis, the QT-NSSPE prepared under optimal conditions was evaluated in terms of microstructure, stability, and in vitro release and the droplet size and drug loading were 15.82 μm and 4.87 mg·mL~(-1), respectively. The shell structure formed by quercetin nanocrystals(QT-NC) on the emulsion droplet surface was observed under a scanning electron microscope(SEM). X-ray diffraction(XRD) showed that the crystallinity of adsorbed QT-NC decreased significantly as compared with the raw QT. There were not significant changes of QT-NSSPE properties after 30 days of storage at room temperature. The in vitro release experiment confirmed that QT-NSSPE has a higher accumulative release rate than the raw QT. All these results indicated that QT-NSSPE has a great stability and a satisfactory in vitro release behavior, which is a promising new oral delivery system for QT.

Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).@*METHODS@#Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively.@*RESULTS@#The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05).@*CONCLUSIONS@#Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

Clinical application and mechanism of traditional Chinese medicine in treatment of lung cancer / 中华医学杂志(英文版)

Lung cancer is a malignant tumor characterized by a rapid proliferation rate, less survivability, high mortality, and metastatic potential. This review focuses on updated research about the clinical application of traditional Chinese medicine (TCM) as an adjuvant therapy to lung cancer treatment and the mechanisms of TCM effect on lung cancer in vitro and in vivo. We summarized the recent 5 years of different research progress on clinical applications and antitumor mechanisms of TCM in the treatment of lung cancer. As a potent adjuvant therapy, TCM could enhance conventional treatments (chemotherapy, radiation therapy, and epidermal growth factor receptors [EGFRs] tyrosine kinase inhibitors [TKIs]) effects as well as provide synergistic effects, enhance chemotherapy drugs chemosensitivity, reverse drug resistance, reduce adverse reactions and toxicity, relieve patients' pain and improve quality of life (QOL). After treating with TCM, lung cancer cells will induce apoptosis and/or autophagy, suppress metastasis, impact immune reaction, and therapeutic effect of EGFR-TKIs. Therefore, TCM is a promisingly potent adjuvant therapy in the treatment of lung cancer and its multiple mechanisms are worthy of an in-depth study.

Research advancement on the relationship between thyroid hormone level and type 2 diabetes mellitus / 中国医师杂志

Type 2 diabetes mullitus is a clinical syndrome characterized by elevated plasma glucose caused by genetic and environmental factors.The basic pathophysiological mechanism is a metabolic disorder caused by defects in insulin secretion and/or insulin action.As a hormone that regulates the growth and basal metabolism of the body,thyroid hormone has a close relationship with type 2 diabetes.This article reviews the relationship between thyroid hormone levels and type 2 diabetes mullitus.

Impact of endplate fracture on clinical efficacy of minimally invasive percutaneous pedicle screwing for thoracolumbar vertebra burst fractures / 中华创伤骨科杂志

Objective To investigate the impact of endplate fracture on the clinical efficacy of minimally invasive percutaneous pedicle screwing for thoracolumbar burst fractures.Methods From September 2012 to June 2016,35 patients with thoracolumbar burst fracture underwent minimally invasive percutaneous pedicle screwing at Department of Orthopaedics,The First Affiliated Hospital to Nanjing Medical University.They were divided into 2 groups according to the severity of endplate fracture:a mild fracture group of 17 cases and a severe fracture group of 18 cases.Their clinical data were recorded and compared between the 2 groups before surgery,before discharge,6 months after surgery and at the last follow-up with respects to kyphosis cobb angle and height compression rate of the injured vertebra,and visual analogue scale (VAS),Oswestry disability index (ODI) and the MOS 36-item Short Form Health Survey (SF-36) scores.Results The kyphosis cobb angle and height compression rate of the injured vertebra,and VAS,ODI and SF-36 scores before discharge,6 months after surgery and at the last follow-up were all significantly improved in all the patients compared to the values before surgery (P ＜ 0.05).There were no significant differences between the 2 groups in the kyphosis cobb angle of the injured vertebra before surgery,before discharge,6 months after surgery or at the last follow-up (P ＞ 0.05).At the last follow-up,the height compression rate of the injured vertebra,and VAS,ODI and SF-36 scores in the mild fracture group were significantly lower than in the severe fracture group (P ＜ 0.05),and the height compression rate of the injured vertebra,and VAS,ODI and SF-36 scores of the severe fracture group were significantly higher than the values 6 months before (P ＜ 0.05).Conclusions The severity of endplate fracture may have no significant impact on the recovery of vertebral height in the early-to-mid stage after minimally invasive percutaneous pedicle screwing for thoracolumbar burst fractures.However,the patients complicated with severe endplate fracture are likely to suffer a height loss of the injured vertebral body and decreased quality of life in the long run.

Applications of current perception threshold evaluations in discovering early diabetic peripheral neuropathy / 中国医师杂志

Diabetic neuropathy is one of the common long-term complications of diabetes,which occurs in the peripheral nervous system and the central nervous system,and its most common type is diabetic peripheral neuropathy (DPN).Diabetic peripheral neuropathy can not only cause pain,numbness and limitation of activity in limbs,but also lead to diabetic foot ulcers even amputations due to hypoesthesia and anesthesia,ultimately affects the quality of life of patients with diabetes and increases the mortality.Nearly half of patients with DPN do not have any clinical symptoms,thus the early detection and diagnosis of diabetic peripheral neuropathy are particularly critical.Current perception threshold (CPT) evaluation is considered as a mean of early detection of DPN,which gains more and more attentions because of its non-invasive feature,simple operation and high sensitivity.So far,there is scarcely any article summarizing CPT evaluations' applications in researching the relationships between DPN and its risk factors.This review will discuss the principles and advantages of CPT evaluations,and its relationship with DPN will also be summarized as follows.

PI3Ks in diabetic cardiomyopathy / 中国医师杂志

Diabetic cardiomyopathy refers to the heart disease without coronary artery disease and hypertension,diabetic patients with ventricular dysfunction.The molecular mechanism of diabetic cardiomyopathy remains unclear.Protein and lipid kinase phosphoinositol 3-kinase (PI3Ks) are thought to regulate cardiac damage in diabetes mellitus.This article reviews the role of PI3K subtypes and downstream signal transduction in the pathogenesis of diabetic cardiomyopathy,including cardiac metabolic regulation,contractility,hypertrophy,cardiomyocyte death and inflammation.

The related research of proprotein convertase subtilisin/Kexin 9 inhibitors and dyslipidemia / 中国医师进修杂志

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor is recently added to the list of effective lipid-lowering drugs in addition to statins, which can reduce low density lipoprotein cholesterol, treat increased low density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) patients. In the past 30 years, the prevalence of dyslipidemia increased significantly. LDL-C characterized dyslipidemia is an important risk factor of ASCVD and a part of metabolic syndrome, which exists before or after or at the same time of the appearance of obesity, diabetes, and glucose intolerance, coronary heart disease and other diseases. Decreasing LDL-C level can significantly reduce the incidence and mortality risk of ASCVD. In this paper, the research on the regulation of dyslipidemia by PCSK9 inhibitors is discussed.

The potential therapeutic effects of glucagon like peptide-1 receptor agonists in patients with diabetes mellitus induced erectile dysfunction / 中国医师进修杂志

Diabetic mellitus induced erectile dysfunction (DIED) is a common complication of type 2 diabetes mellitus (T2DM), which seriously affects the physical and mental health of male T2DM patients. The occurrence of DIED involves a variety of pathophysiological changes such as vascular tissue, nerve, endocrine and so on. But the traditional treatment of erectile dysfunction is not ideal for DIED. Glucagon like peptide (GLP)- 1 receptor agonist has been widely used as a new drug for the treatment of diabetes, and the representative drugs are exenatide and liraglutide. Existing research shows that it can improve endothelial cell function, neuropathy and sex hormone secretion, reduce body weight and insulin resistance. Therefore, these drugs may be a new choice for patients with DIED.

Determination Method Improvement for Chloramphenicol Hydrocortisone Ear Drop / 中国药师

Objective:To establish a method for the determination of chloramphenicol and hydrocortisone in chloramphenicol hy-drocortisone ear drop. Methods:An HPLC method was used with a Shiseido SPOLAR C18 column (250 mm ′4. 6 mm, 5 mm). The mobile phase was 0. 01 mol·L-1 sodium heptane sulfonate buffer solution (6. 8 g potassium dihydrogen phosphate was dissolved in 0. 01 mol · L-1 heptane sodium sulfonate buffer solution and diluted to 1000 ml, 5 ml triethylamine was added and mixed, and then the pH was adjusted to 2. 5 by phosphoric acid)-methanol (40︰60). The column temperature was 30℃ and the flow rate was 1. 0 ml · min-1 . The detection wavelength was 245 nm and the injection volume was 10 μl. Results: Chloramphenicol and hydrocortisone had a good linear relationship within the range of 50. 26-753. 84 μg · ml-1 ( r =0. 9996 ) and 10. 93-163. 92 μg · ml-1 ( r =1. 0000), respectively. The average recovery of chloramphenicol was 100. 21% and RSD was 0. 48%(n=9). The average recovery of hydrocortisone was 100. 82% and RSD was 0. 37% (n=9). Conclusion:The method has the advantages of high specificity, good reproducibility and high precision, and can be used as a method for the determination of chloramphenicol and hydrocortisone in chlor-amphenicol hydrocortisone ear drop.

Progress of serum cystatin C in patients with type 2 diabetes mellitus and the complications / 中国综合临床

Objective Cystatin C (CysC) is a cysteine protease inhibitor,is widely expressed in human eukaryotic cells,CysC involved in diabetic nephropathy,retinopathy,peripheral vascular disease and type 2 diabetes,insulin resistance occurs Development,as a predictor of type 2 diabetes and complications

Determination of residual organic solvents in 2-2-methyl-4-2-4-(trifluoromethyl) phenyl pyrimidin-4-yl methylsulfanyl phenoxy acetic acid by capillary gas chromatography / 中国药学杂志

OBJECTIVE: To establish a capillary GC method for the determination of residual solvents including ethanol, acetoni-trile, acetone, isopropanol, ethyl acetate, dioxane and THF in 2-[2-methyl-4-[[2-[4-(trifluoromethyl) phenyl] pyrimidin-4-yl] methylsulfanyl] phenoxy] acetic acid. METHODS: The residual organic solvents were separated on DB-1capillary column (30 m × 0.53 mm, 5.00 μm). FID was used as detector with a temperature of 250°C, and the inlet temperature was 160°C. The carrier gas was nitrogen, and the column temperature was programmed set. The contents of residual solvents were calculated by external standard method. RESULTS: The seven residual organic solvents were completely separated, the recovery rates and linear relationship were good, and three batches of samples all met the requirements. CONCLUSION: The method is simple, accurate, and reproducible, so it can be used for the detection of seven residual organic solvents in the raw.

Evaluation of brain dysfunction in chronic anoxic encephalopathy with evoked potentials / 中国应用生理学杂志

<p><b>AIM</b>To explore the relationship between evoked potentials (EPs) and chronic anoxic brain damage by chronic intermittent hypoxia (CIH), and provide theory evidence for diagnosis and treatment of anoxic encephalopathy.</p><p><b>METHODS</b>BAEP and SLSEP were recorded in rat model with CIH (hypoxia group) and rat with normoxia (normal group). Morris water maze was used to observe learning and memory ability. Immunohistochemical method was used to investigate the expression levels of caspase-3 in brain tissue.</p><p><b>RESULTS</b>The peak latency (PL) of wave I, III, V and the interpeak latency (IPL) of wave III - V, I - V in BAEP in hypoxia group were much longer than that of in normal group (P < 0.05). The PL of wave N1, P1 of SEP in hypoxia group were much longer than that of in normal group (P < 0.05). In the water mase test, the escape latency (EL) of hypoxia group was much longer than normal group (P < 0.01). The number of caspase-3 positive cells in hypoxia group was much larger than that of in normal group (P < 0.05). There was a positive correlation among BAEP, SLSEP, the number of caspase-3 positive neuron and EL of water mase.</p><p><b>CONCLUSION</b>The alteration of BAEP and SLSEP has an apparent correlation with chronic anoxic brain damage. This provides theory evidence for diagnosis and treatment of anoxic encephalopathy.</p>

Using pre-warning intervention to prevent the acute bed sore among patients who have accepted the cardiac operation under direct vision / 中国实用护理杂志

Objective To evaluate the effect of using pre-warning intervention in the course of nursing patients who have accepted the cardiac operation under direct vision. Methods Using pre-warning intervention in 736 patients who have accepted the intracardiac surgery under extracorporeal circulation. Results There were not patients have aucte bed sore after using the pre-warning intervention. Conclusion Using pre-warning intervention can prevent the acute bed sore effectively among the preoperative patients,and then reduce the unnecessary dissension between nurses and patients,improve the quality of nursing and the patients′ satisfaction.