[Correlation of cognitive function with intracranial lesions and the degree of depression and anxiety in patients with neuromyelitis optica spectrum disorders].

Objective: To investigate the correlation of cognitive dysfunction with intracranial lesions and symptoms of depression and anxiety in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: Thirty-one NMOSD patients (7/24 males/females) were enrolled in the Department of Neurology of the Sixth Medical Center of the PLA General Hospital from August 2019 to August 2022. The average age was 42±13 years, and the average education level was 12 (9, 12) years. There were 30 healthy controls, 11/19 males/females, with an average age of 47±9 years and an average education of 12 (9, 15) years. The general clinical data and imaging data were collected, and the subjects were assessed on their cognition, anxiety and depression using the assessment scale approved at home and abroad. A cross-sectional study was conducted on them. The t-test or Wilcoxon test was used for inter-group comparison, and Pearson test or Spearman test was used to explore the correlation between the cognition of NMOSD patients and their intracranial lesions, depression and anxiety. Results: Compared with the healthy control group, NMOSD patients had significantly lower scores on MoCA (Z=-3.10,P=0.002), CRAVLT-N7 (Z=-5.12, P<0.001), CRAVLT-N8 (t=-4.40, P<0.001), ROCF-R (t=-3.10,P<0.01), ROCF-C (Z=-2.72,P<0.01), PASAT-3 (Z=-2.71,P<0.01), PASAT-2 (Z=-3.14,P<0.01), and CWT-A (Z=-3.10,P<0.01)scales. Frontal lobe lesions were negatively correlated with PASAT-2 (r=-0.448, P=0.012) scores, temporal lobe lesions were negatively correlated with CRAVLT-N9 (r=-0.564, P=0.001), and parietal lobe lesions were negatively correlated with MoCA (r=-0.374, P=0.038), PASAT-3 (r=-0.426, P=0.017), and PASAT-2 (r=-0.459, P=0.009) scores; The scores of MoCA (r=-0.392, P=0.029), CRAVLT-N6 (r=-0.396, P=0.028), CRAVLT-N7 (r=-0.415, P=0.020), CRAVLT-N8 (r=-0.406, P=0.023), PASAT-3 (r=-0.537, P=0.002) and PASAT-2 (r=-0.495, P=0.005) scales were negatively correlated with the scores of HAMD assessment, and the scores of PASAT-3 (r=-0.499, P=0.004) and PASAT-2 (r=-0.452, P=0.011) were negatively correlated with the scores of HAMA. Conclusions: The cognitive function of patients with NMOSD is significantly reduced, involving multiple cognitive domains. The cognitive function is affected by the distribution of intracranial lesions and the degree of depression and anxiety.

[Relationship between nutritional factors and clinical outcome in children with tuberculous meningitis].

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs. 32 cases (64.0%), 20 cases (32.3%) vs.8 cases (16.0%), 33 cases (53.2%) vs. 15 cases (30.0%), 30 cases (48.4%) vs. 2 cases (4.0%), 59 cases (95.2%) vs. 1 case (2.0%),41 cases (66.1%) vs.18 cases (36.0%), 1 406 (1 079, 2 068) vs. 929 (683, 1 208) mg/L, χ2=3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z=4.35, all P<0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs. (41±4) g/L, (110±17) vs. (122±14) g/L, 1.4 (1.0, 2.0)vs. 2.3 (1.6, 3.8)×109/L, 7.8 (6.3, 10.0)×109 vs. 10.0 (8.3, 12.8)×109/L, 1.0 (0.8, 1.6) vs. 2.1 (1.3, 2.5) mmol/L, t=-6.15, -4.22, Z=-4.86, -3.92, -4.16, all P<0.05).Increased levels of serum albumin (OR=0.812, 95%CI:0.705-0.935, P=0.004) and lymphocyte count (OR=0.609, 95%CI:0.383-0.970, P=0.037) may reduce the nutritional risk of children with TBM; while convulsions (OR=3.853, 95%CI:1.116-13.308, P=0.033) and increased level of CSF protein (OR=1.001,95%CI:1.000-1.002, P=0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs. 15 cases(30.0%), 31 cases (50.0%) vs.8 cases (16.0%), χ2=23.50, 14.10, all P<0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs. (18±7) d, t=4.38, P<0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.

[Analysis of characteristics of collateral circulation pathways in dizziness patients caused by severe bilateral vertebral artery stenosis/occlusion].

The clinical data of 47 patients [41 males, 6 females, aged (62±7) years] treated at the Department of Neurology of the Sixth Medical Center of PLA General Hospital from October 2018 to October 2020 who were diagnosed with severe bilateral vertebral artery stenosis/occlusion through Digital Subtraction Angiography (DSA) were retrospectively collected, and the characteristics of the compensatory pathways of collateral circulation were determined. Results showed that there were 8 intracranial and extracranial compensatory pathways, with posterior communicating artery as the major type (21 cases) for intracranial ones and deep carotid artery as the major type (16 cases) for extracranial ones. As the establishment of the compensatory pathway is closely related to the lesion site, DSA assessment for patients with severe bilateral vertebral artery stenosis/occlusion is helpful for clinicians to make judgement on prognosis of patients and choose individualized treatment plans.

[Collateral circulation pathway in patients with basilar artery occlusion/severe stenosis: a single-center case series].

Objective: To investigate the collateral circulation compensation model in patients with favorable prognosis of basilar artery occlusion/severe stenosis treated with drugs or endovascular therapy. Methods: Clinical data of patients with basilar artery occlusion/severe stenosis and good clinical outcome were retrospectively collected in the Department of Neurology, Sixth Medical Center of PLA General Hospital from January 2019 to January 2020. They were divided into intensive drug therapy group and combined endovascular therapy group. The number and ways of collateral compensation pathway described by digital substraction angiography (DSA) were analyzed, and the characteristics of the collateral compensation model were summarized. SPSS22.0 software was used for statistical analysis, and the constituent ratio (%) was used for statistical description of the enumeration data. Results: A total of 32 eligible patients were included, including 27 males and 5 females, with an average age 45-76 (59±10) years. The compensation model included posterior communicating artery-posterior cerebral artery (13 cases, 40.6%), posterior communicating artery-posterior cerebral artery-basilar artery (10 cases, 31.2%), cerebellar artery-anastomotic branches of superior cerebellar artery (8 cases, 25.0%), anterior choroid artery-anastomotic branches of posterior choroid artery (2 cases, 6.2%), collateral circulation not established (11 cases, 34.4%).In drug treatment group, collateral compensation was found in the majority (14/15), with mainly posterior communicating artery (10/14).Most patients in combined treatment group did not develop collateral compensation (10/17), anastomotic branches of PICA-SCA were the main routes (6/7). Conclusion: In patients with basilar artery occlusion/severe stenosis, favorable clinical outcome can be achieved in both groups of patients treated with intensive drug therapy or endovascular therapy.

MiR-20a acted as a ceRNA of lncRNA PTENPL and promoted bladder cancer cell proliferation and migration by regulating PDCD4.

OBJECTIVE: Bladder cancer is the most frequent tumor of the urinary system. Despite variety of new treatment options, bladder cancer remains a main global medical problem. Our purpose was to explore the potential molecular and therapeutic targets of bladder cancer diagnosis. PATIENTS AND METHODS: The qRT-PCR was used to assess the expression of miR-20a in tissues and cell lines. Counting Cell Kit-8 (CCK-8) assay was carried out to evaluate cell proliferation. Cell migration was calculated using the transwell assay. RESULTS: The expression of miR-20a increased and PDCD4 decreased in bladder cancer tissues compared with normal tissues. Overexpression of miR-20a promoted T24 cell proliferation and migration, while miR-20a inhibitor suppressed cell proliferation and migration. MiR-20a targeted PDCD4 to regulate its expression in T24 cells. MiR-20a is inversely related to PDCD4 and PTENPL in bladder cancer tissues. Upregulation of PDCD4 suppressed T24 cell proliferation and migration. CONCLUSIONS: The PTENP1/miR-20a/PTEN axis was involved in the progression of bladder cancer. Our study investigated the function of miR-20a in bladder cancer and provided new insights into the treatment of bladder cancer.

Giant caloric effects enhanced by the helix polarization at the 180° domain wall in tetragonal BaTiO3.

The electrocaloric and elastocaloric properties at the 180° domain wall in the tetragonal BaTiO3 are studied using the Landau-Ginzburg-Devonshire model as a function of the domain wall rotation angle α. The Ising-Bloch character is predicted at the 180° domain wall in tetragonal BaTiO3 under the flexoelectric effect. The electric field-induced adiabatic temperature change (ΔT E) which is induced by the Bloch-type polarization component depends on α, and a giant positive ΔT E appears at α = (π + 12n)/24 where n is an integer. The asymmetry of ΔT E is found around the Bloch-type domain wall. The Bloch-type polarization component has a little contribution to the stress-induced adiabatic temperature change. This calculation indicates a contribution of helix polarization at the domain wall on the caloric effects (CEs) in the ferroelectric materials.

[Prediction of pelvic floor muscle function in stress urinary incontinence].

Objective: To explore the predictive effect of pelvic floor muscle function on stress urinary incontinence (SUI) . Methods: A total of 258 women in gynecological outpatients at Fuzhou General Hospital were evaluated the pelvic floor muscle function by intravaginal manometery, then all of outpatients were divided into urinary incontinence group and non-incontinence group, and compared pelvic floor muscle function and clinical characteristic to establish prediction model of SUI by classification tree and analyse the predictive role of pelvic floor muscle function for SUI. Results: There were significant difference in body mass index [BMI; (22.8±2.9) vs (21.5±2.7) kg/m2, P<0.05], maximum newborn weight [ (3 396±424) vs (3 284±384) g, P<0.05] between urinary incontinence group (n=114) and non-incontinence group (n=144) . However, there were no significant differences in age, parity and mode of delivery between two groups (all P>0.05) . There were significant differences (all P<0.01) in maximum vaginal pressure [ (21±7) vs (35±9) mmHg (1 mmHg=0.133 kPa) ], average pressure [ (13±7) vs (23±9) mmHg], fatigue [ (-65±20) % vs (-46±17) %] and collecting time [ (1.0±0.6) vs (0.8±0.5) s] between two groups. Prediction model, which obtained by classification tree analysis with the affecting factors of SUI (including BMI, maximum vaginal pressure, fatigue and collecting time) , suggested that the incidence of SUI was 88.6% (70/79) , when maximum vaginal pressure ≤26.2 mmHg. While, when maximum vaginal pressure was greater than 28.2 mmHg, there was no occurrence of SUI (0/7) . But it would increase, when BMI >22.6 kg/m2. Conclusions: The occurrence of SUI is related to the BMI and pelvic floor muscles function. It would increase the risk of SUI with vaginal maximum pressure (≤26.2 mmHg) and BMI (>22.6 kg/m2) . While there is almost no SUI, while vaginal maximum pressure >28.2 mmHg. To select high-risk group of SUI and intervene early according to the prediction model, which may be make sense of reducing incidence of SUI.

Giant electrocaloric effect in a wide temperature range in PbTiO3 nanoparticle with double-vortex domain structure.

Electrocaloric effect (ECE) has the potential applications in solid-state refrigeration with the features of high efficiency and environmentally friendly. Large adiabatic temperature change in a wide temperature range is needed for electrocaloric effect to meet the requirement of commercially application. In this work, giant electrocaloric effect is found in PbTiO3 nanoparticle with double-vortex domain structure in a wide temperature range by using phase field method, which the lowest and highest adiabatic temperature change (ΔT) is 7.2 K and 16.5 K, respectively. The influence of misfit strain on the ECE of PbTiO3 nanoparticle with the double-vortex domain structure is investigated, and results show that the compress misfit strain can enhance the ECE, but the tensile misfit strain reduces the ECE. This work reveals a way to obtain giant ECE of ferroelectric materials by domain engineering and strain engineering in a wide temperature range.

[Evaluation of transperineal sonography for lower urinary tract symptoms after pelvic floor reconstruction].

Objective: To evaluate transperineal sonography for lower urinary tract symptoms after pelvic floor reconstruction. Methods: Eighty-three patients with severe pelvic organ prolapse received surgeries in Fuzhou General Hospital from September 2014 to September 2015, dividing into two groups: 27 patients were selected to receive transvaginal mesh (TVM) pelvic floor reconstruction surgery with tension-free vaginal tape-Abbrevo (TVT-Abbrevo) incontinence surgery, named TVM+TVT-Abbrevo group; 56 patients were selected to receive TVM pelvic floor reconstruction surgery only, named TVM group. The ultrasonic parameters at rest, on contraction and Valsalva condition respectively were observed and measured, including the bladder neck descent (BND), urethral rotation angle, retrovesical angle, levator urethra gap (LUG), the existence of bladder neck funneling, position of the tape, by using 2D and 3D transperineal ultrasound. Results: The two groups were compared with the ultrasonic parameters before and after operation: two groups of patients with postoperative BND [(2.3±0.5) versus (3.1±0.7) cm, (1.6±0.4) versus (3.6±0.4) cm] were significantly reduced, the difference was statistically significant (P=0.02, P<0.01). The two groups of LUG before and after operation [(3.62±0.45) versus (3.26±0.92) cm, (2.96±0.47) versus (2.72±0.38) cm] both had significant difference by maximum Valsalva (P<0.01, P=0.04). There was statistical significance difference of urethral rotation angle in TVM+TVT-Abbrevo group by maximum Valsalva (P=0.01). Observation of morphology: (1) 2 patients with difficulty in urination in TVM+TVT-Abbrevo group, ultrasound showed when the position of the bladder down the urethra discount; 4 patients with stress urinary incontinence (SUI), ultrasound showed slings off or release. (2) One patient with difficulty in urination in TVM group, but ultrasound showed lower urinary tract anatomy were normal; 5 patients with SUI, ultrasound showed the position of the bladder neck were significantly lower in 3 patients, showing high mobility, and the other 2 patients had a larger urethral diameter, showing a tendency of natural deletion. Conclusion: s Anatomy of lower urinary tract could be clearly showed by transperineal sonography. This could provide imaging support for the diagnosis of lower urinary tract symptoms after pelvic floor reconstruction.

[Value of pudendal nerve stimulation for predicting the stress urinary incontinence following pelvic prolapse surgery].

OBJECTIVE: To seek the predictive value of pudendal nerve function that need preventive anti-incontinence surgery at the same time following pelvic prolapse surgery in severe pelvic organ prolapse (POP) patients. METHODS: Seventy women completed this study from January 2014 to June 2015 in Fuzhou General Hospital of Nanjing Military Command, dividing into four groups: POP with or without coexisting occult stress urinary incontinence (OSUI) in preoperation, women with persistent stress urinary incontinence (SUI) in postoperation, women without SUI in postoperation. The pudendal nerve function in preoperation was measured by using Solar Urodynamic Neuro Module, including pudendal nerve terminal motor latency (PNTML), and amplitude. RESULTS: There were statistical significance on bilateral PNTML between POP coexisting OSUI group and only severe POP group [(2.62±0.23) versus (2.40±0.26) ms in right of PNTML, (2.55± 0.21) versus (2.37 ±0.30) ms in left of PNTML; all P<0.05], but no statistical significance on bilateral amplitude (P>0.05). Compared de novo SUI group with POP group in postoperation, de novo SUI group's right of PNTML was significantly increased [(2.74±0.16) versus (2.47±0.26) ms; P< 0.05]; and the right of PNTML was extending 2.5 standard deviation at least compared with the health's [(2.10±0.20) ms]. CONCLUSIONS: The PNTML of pudendal nerve of POP coexisting OSUI is severe than only severe POP, the velocity of nerve conduction is slowing, and PNTML extension has a predictive value for postoperative urinary incontinence. When the right of PNTML of preoperative POP increased by at least 2.5 standard deviations than health's, the risk of SUI postoperative strongly increased, and a anti-incontinence surgery at the same time following pelvic prolapse surgery should be adviced.

Role of inflammatory responses in the pathogenesis of human cerebral aneurysm.

We aimed to detect expressional profiles of intracellular cell adhesion molecule-1 (ICAM-1), nuclear factor-kappa B (NF-κB), and monocyte chemoattractant protein-1 (MCP-1) in human cerebral aneurysm, in order to investigate the effect of chronic inflammation on the pathogenesis of cerebral aneurysm. Samples from 40 cases of human cerebral aneurysms diagnosed at our hospital were selected along with 20 normal cerebral artery samples. Western blotting and immunohistochemical (IHC) staining were used to reveal expressional profiles of ICAM-1 and NF-κB in the aneurysmal wall of patients and normal cerebral artery tissues. Reverse transcription (RT)-PCR was employed to detect changes in transcript levels of MCP-1 mRNA. Western blotting showed significantly higher expressions of ICAM-1 and NF-κB in patients with cerebral aneurysm compared to the normal group (P < 0.01), which was consistent with IHC staining results. RT-PCR revealed significantly higher MCP-1 transcripts in cerebral aneurysm tissues compared to the normal group (P < 0.01), in addition to a positive relationship between ICAM-1 and NF-κB expression levels. In conclusion, expression levels of ICAM-1, NF-κB, and MCP-1 in patients are significantly elevated, suggesting an enhanced chronic inflammatory response and a significant correlation between inflammatory factors/adhesion molecules and the pathogenesis of cerebral aneurysm.

Spinal protein kinase Mζ contributes to the maintenance of peripheral inflammation-primed persistent nociceptive sensitization after plantar incision.

BACKGROUND: Previous studies suggest that persistent post-surgical pain (PPSP) is correlated with preoperative pain status and amplification of central sensitization. Protein kinase Mζ (PKMζ) is an essential substrate of the late long-term potentiation underlying central sensitization, which is one mechanism of pain memory formation. However, the potential contributions of spinal PKMζ to PPSP, a condition in which preoperative pain is prevalent, are not known. METHODS: Here, a modified 'hyperalgesia priming' model was established to simulate the clinical situation. This model used intraplantar injections of carrageenan (Car) as priming stimuli to elicit persistent nociceptive sensitization after plantar incision in rats. Upon treatment with PKMζ inhibitor ZIP, Scr-ZIP or protein kinase Cs (PKCs) inhibitor NPC-15437, altered behaviour and spinal PKMζ/PKCs expression were observed. RESULTS: A long-lasting hypersensitivity induced by Car-priming was identified and precipitated by subsequent plantar incision in this 'two-hit' paradigm. Post-treatment with ZIP, but not Scr-ZIP and NPC-15437, after the resolution of Car-priming selectively relieved hypersensitivity. In contrast, pre-priming NPC-15437 treatment only prevented Car-induced initial transient hyperalgesia. Immunoassays showed a significant decrease in spinal PKMζ expression after plantar incision with post-priming ZIP treatment as compared with Scr-ZIP and NPC-15437, but no notable differences in PKCs expression were observed. CONCLUSIONS: Spinal PKCs solely contribute to the initial induction of persistent pain, whereas PKMζ plays an essential role in spinal plasticity storage. PKMζ is responsible for the maintenance of peripheral inflammation-primed PPSP. Therefore, spinal PKMζ may be a therapeutic target to prevent surgery-induced chronic pain in patients with preoperative pain.

Roles of Fas/Fasl, Bcl-2/Bax, and Caspase-8 in rat nonalcoholic fatty liver disease pathogenesis.

The aim of this study was to investigate the roles of Fas/FasL, Bcl-2/Bax, and Caspase-8 mRNA expressions in nonalcoholic fatty liver disease (NAFLD). The apoptosis percentage was measured by flow cytometry, the immunohistochemical assay was performed for the determination of Fas, FasL, Bcl-2, and Bax expressions, and a real-time polymerase chain reaction (PCR) assay was performed to detect Caspase-8 mRNA expression. Flow cytometry showed that the apoptosis percentage of the rat liver in the experimental group increased, which increased more obviously with the extension of modeling time. Immunohistochemistry showed that with increasing hepatic steatosis, Fas and FasL protein staining intensified and the number of positive cells increased; the number of positive cells for Bcl-2 and Bax gradually increased on the 4th, 8th, and 12th weeks in the experimental group, whereas the Bcl-2/Bax ratio decreased. The real-time PCR assay showed that Caspase-8 mRNA expression increased with increasing hepatic steatosis and inflammation, exhibiting a progressively rising trend. Hepatocyte apoptosis could promote NAFLD progression; Fas, FasL, and Caspase-8 mRNA activation were important contributing factors to NAFLD. The upregulation of Bax and Bcl-2 expression might be one important mechanism of the apoptosis in NAFLD.

Mode-dependent effect of high-frequency electrical stimulation of the anterior thalamic nucleus on amygdala-kindled seizures in rats.

Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. The present study aimed to investigate the effects of high frequency stimulation (HFS) targeting the ANT on amygdala-kindled seizures in Wistar rats in two different stimulation modes i.e. pre-treatment and post-treatment stimulations, mimicking the scheduled and responsive stimulations in clinical use respectively. When fully-kindled seizures were achieved by daily amygdala kindling (1 s train of 1 ms pulses at 60 Hz), HFS (15 min train of 100 µs pulses at 150 Hz and 450-800 µA) was applied in two modes for 10 days. Bilateral post-treatment with HFS reduced the incidence of generalized seizures and the mean behavioral seizure stage and shortened average afterdischarge duration (ADD) and generalized seizure duration (GSD), while bilateral pre-treatment with HFS resulted in a similar but much weaker inhibition of seizures. On the other hand, we also found the two stimulation modes both increased the afterdischarge threshold (ADT) and the differences of current intensity between ADT and generalized seizure threshold (GST) i.e. Δ(GST-ADT). However, Δ(GST-ADT) increased by at least 20 µA in bilateral post-treatment group, while less in bilateral pre-treatment group. Additionally, unilateral post-treatment with HFS failed to inhibit seizures. Our data show that anti-epileptic effect of bilateral post-treatment with HFS of ANT is much stronger than that of bilateral pre-treatment HFS, indicating bilateral responsive stimulation might be more appropriate for clinical anti-epileptic treatment of ANT HFS.

Considerable Enhancement of Field Emission of SnO(2) Nanowires by Post-Annealing Process in Oxygen at High Temperature.

The field emission properties of SnO(2) nanowires fabricated by chemical vapor deposition with metallic catalyst-assistance were investigated. For the as-fabricated SnO(2) nanowires, the turn-on and threshold field were 4.03 and 5.4 V/mum, respectively. Considerable enhancement of field emission of SnO(2) nanowires was obtained by a post-annealing process in oxygen at high temperature. When the SnO(2) nanowires were post-annealed at 1,000 degrees C in oxygen, the turn-on and threshold field were decreased to 3.77 and 4.4 V/mum, respectively, and the current density was increased to 6.58 from 0.3 mA/cm(2) at the same applied electric field of 5.0 V/mum.

Molecular characterization and PCR detection of a deletional HPFH: application to rapid prenatal diagnosis for compound heterozygotes of this defect with beta-thalassemia in a Chinese family.

Hereditary persistence of fetal hemoglobin (HPFH) is one of the hemoglobinopathies in which the fetal gamma-globin genes remain active in adult life. Most HPFHs are caused by a large deletion involving a variable extent of DNA segment on the beta-globin gene cluster. We report the molecular defects associated with a deletional HPFH, which has previously been described in Cambodians and Vietnamese, in two unrelated Chinese individuals. To define the sequence around the breakpoints of the deletion, both the deletion junction fragment and the normal DNA across the breakpoints were cloned by PCR and sequenced. We found that the 5' breakpoint is located between nucleotides 986 and 987 upstream from the startpoint of the beta-globin gene, which further confirmed the Southeast Asian (SEA) HPFH deletion previously determined, whereas the 3' breakpoint, which is clarified for the first time by us, lies approximately 2.3 kb downstream from the 3' HS1 site of the beta-globin gene. It is suggested that deletions were the result of a non-homologous recombination event. Based on our novel sequence data, we designed a PCR amplification method with three primers bridging the 3' breakpoint. With this method and reverse dot blot (RDB) for detecting beta-thalassemia mutations, a Chinese family that had a 6-year-old propositus with severe thalassemia intermediate and that had requested prenatal diagnosis for the second pregnancy was found to be compound heterozygotes of HPFH defects with beta-thalassemia. The fetal genomic DNA diagnosis showed the same results as those in propositus, i.e., both of them inherited the deletion from their mother and inherited a codons 14-15 (+G) frameshift mutation causing beta-thalassemia from their father.

Streptozotocin induced cardiomyopathy in diabetic rats.

Microscopic quantitative cardiomyopathy was previously reported in spontaneous diabetic biobreeding (BB) rats, but the nature of the lesions remains obscure. To further study the specificity of cardiomyopathy in streptozotocin-diabetic rats and discuss the existence of diabetic heart disease, we compared 40 streptozotocin-diabetic rats (D group) with 40 normal control rats (C group) at various durations in plasma glucose, fructosamine, plasma lipid, left ventricular enzyme contents and alterations of myocardial cells and coronary artery tree under electron and light microscope respectively. In 4 weeks, D rats showed myocardial mitochondrial swelling and degeneration, whereas at 8 weeks, myocardial enzyme contents markedly decreased, and myocardial lesions were more conspicuous with disruption of myocardial cells, formation of myocardial contraction bands, dilatation of intercalated discs, deposition of glycogen granules, etc. At 11 weeks, microscopic changes were essentially similar, whereas the decrease of enzyme contents became more conspicuous. During the 11 weeks, persistent and marked hyperglycemia and elevation of fructosamine were observed, however, no abnormalities were found along the coronary artery tree in the D rats. The results indicated that cardiomyopathy is diabetes specific, and exists independently as one of the three important components of diabetic heart disease.

[Chemical synthesis and cloning of Plasmodium falciparum 45 peptide antigen gene].

We have synthesized a 162 bp gene of human Plasmodium falciparum hybrid peptide antigen by the solid-phase phosphoramidite method with ABI 381A DNA synthesizer. The gene encodes three fragments of the relative molecules 83 kDa, 55 kDa and 35 kDa merozoite-specific proteins and two CS repeats or four peptides. The gene with the designed two cohesive ends was divided into 8 fragments to be synthesized. All synthetic fragments were annealed and ligated with T4 DNA ligase to form double DNA chain. This synthetic gene was recombined with P-Blue script as vector and transformed into E. coli JM109. The positive recombinants were screened out by dot hybridization and enzyme analysis. The DNA sequence analysis showed that the synthesized human Plasmodium falciparum hybrid peptide antigen gene was identical with the designed one. (Figs. 1-4).

[Alterations in the sorbitol pathway and Na(+)-K(+)-ATPase activity of peripheral nerve of alloxan-induced diabetic rats].

Sorbitol pathway activity, myo-inositol content and ouabain-sensitive and ouabain-resistant ATPase activities were measured in homogenates of the sciatic nerve from alloxan-induced diabetic rats for 4, 8 and 12 weeks. Compared with the age-matched control, glucose, fructose and sorbitol contents of the sciatic nerve from diabetic rats for 4, 8 and 12 weeks were increased respectively to a level of 3-4 fold, 3-5 fold and 6-9 fold of those of the control rats. Myo-inositol was reduced approximately 50%. There was a significant decrease (P less than 0.01) in total ATPase, ouabain-sensitive and ouabain-resistant ATPase activities. These changes could be relevant to the development of diabetic neuropathy.