Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron.

BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity.RESULTSThe 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigator-initiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay.CONCLUSIONThese results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections.TRIAL REGISTRATIONwww.chictr.org.cn, ChiCTR2200066525.FUNDINGThe National Science and Technology Major Project (2017ZX10202203), the National Key Research and Development Program of China (2018YFA0507100), Guangzhou National Laboratory (SRPG22-015), Lingang Laboratory (LG202101-01-07), Science and Technology Commission of Shanghai Municipality (YDZX20213100001556), and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001).

QiShenYiQi pill inhibits atherosclerosis by promoting TTC39B-LXR mediated reverse cholesterol transport in liver.

BACKGROUND: Tetranucleotide repeat domain protein 39B (TTC39B) was found to combine with ubiquitin ligase E3, and promote the ubiquitination modification of liver X receptor (LXR), which led to the inhibition of reverse cholesterol transport and development of atherosclerosis. QiShenYiQi pill (QSYQ) is a modern Chinese patent drug for treating ischemic cardiovascular diseases, the underlying mechanism is found to promote the expression of LXR-α/ ATP-binding cassette transporter G5 (ABCG5) in the liver of atherosclerotic mice. PURPOSE: The aim of this study is to investigate the effect of QSYQ on TTC39B-LXR mediated reverse cholesterol transport in atherosclerotic mice. STUDY DESIGN AND METHODS: Male apolipoprotein E gene knockout mice (7 weeks old) were fed with high-fat diet and treated with low dose of QSYQ (QSYQ-l, 0.3 g/kg·d), high dose of QSYQ (QSYQ-H, 1.2 g/kg·d) and LXR-α agonist (LXR-A, GW3965 10 mg/kg·d) for 8 weeks. C57BL/6 J mice were fed with normal diet and used as negative control. Oil red O staining, HE staining, ELISA, RNA sequencing, western blot, immunohistochemistry, RT-PCR, cell culture and RNA interference were performed to analyze the effect of QSYQ on atherosclerosis. RESULTS: HE staining showed that QSYQ reduced the atherosclerotic lesion significantly when compared to the control group. ELISA measurement showed that QSYQ decreased serum VLDL and increased serum ApoA1. Oil Red O staining showed that QSYQ reduced the lipid content of liver and protect liver function. Comparative transcriptome RNA-sequence of liver showed that DEGs after QSYQ treatment enriched in high-density lipoprotein particle, ubiquitin ligase complex, bile secretion, etc. Immunohistochemical staining and western blot proved that QSYQ increased the protein expression of hepatic SR-B1, LXR-α, LXR-ß, CYP7A1 and ABCG5. Targeted inhibiting Ttc39b gene in vitro further established that QSYQ inhibited the gene expression of Ttc39b, increased the protein expression of SR-B1, LXR-α/ß, CYP7A1 and ABCG5 in rat hepatocyte. CONCLUSION: Our results demonstrated the new anti-atherosclerotic mechanism of QSYQ by targeting TTC39B-LXR mediated reverse cholesterol transport in liver. QSYQ not only promoted reverse cholesterol transport, but also improved fatty liver and protected liver function.

miR-124 and VAMP3 Act Antagonistically in Human Neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor that affects developing nerve cells in the fetus, infants, and children. miR-124 is a microRNA (miRNA) enriched in neuronal tissues, and VAMP3 (vesicle-associated membrane protein 3) has been reported to be an miR-124 target, although the relationship between NB and miR-124 or VAMP3 is unknown. Our current work identified that miR-124 levels are high in NB cases and that elevated miR-124 correlates with worse NB outcomes. Conversely, depressed VAMP3 correlates with worse NB outcomes. To investigate the mechanisms by which miR-124 and VAMP3 regulate NB, we altered miR-124 or VAMP3 expression in human NB cells and observed that increased miR-124 and reduced VAMP3 stimulated cell proliferation and suppressed apoptosis, while increased VAMP3 had the opposite effects. Genome-wide mRNA expression analyses identified gene and pathway changes which might explain the NB cell phenotypes. Together, our studies suggest that miR-124 and VAMP3 could be potential new markers of NB and targets of NB treatments.

Transcriptome analysis reveals immune regulation in the spleen of koi carp (Cyprinus carpio Koi) during Aeromonas hydrophila infection.

A. hydrophila (Aeromonas hydrophila) is one of the most hazardous pathogenic microorganisms threatening the aquaculture industry and exhibits zoonotic-like characteristics. This study was designed to investigate the differential gene expression and pathway enrichment in the spleen of koi carp (Cyprinus carpio koi) upon A. hydrophila infection. The Illumina NovaSeq 6000 sequencing platform was used to identify 252 DEGs (differentially expressed genes), including 112 upregulated genes and 140 downregulated genes, in the spleens of koi carp challenged with A. hydrophila compared to those in the spleens of koi carp treated with PBS (phosphate-buffered saline). DEGs were shown to be involved in 133 pathways by KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Numerous immunological disease-related pathways, such as the immune defense network for IgA production, Staphylococcus aureus infection, and antigen processing and presentation, were enriched in the DEGs. In addition, the expression levels of 10 randomly screened DEGs, including the inflammatory factor nlrp3 (NOD-like receptor family pyrin domain containing 3), cytokine il-8 (interleukin-8), c2 (complement c2), c3 (complement c3), and the lipid mediator cox1 (cyclooxygenase-1), were compared by qPCR. The results showed that six genes, including il-8, cox1, and nlrp3, were upregulated according to both RNA-seq and qPCR validation, while four, including c2 and c3, showed downregulated expression. This result verified a strong correlation between the RNA-seq and qPCR datasets at the expression level. Moreover, this study provided splenic transcriptome data for koi carp during A. hydrophila infection and provided theoretical support for future drug development.

QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/ß-ABCA1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: QiShenYiQi pill (QSYQ), a Chinese compound medicine, originate from BuYangHuanWu decoction in the Qing dynasty, and has been used to treat ischemic cardiovascular diseases for more than two hundred years in China. Multi-central randomized double-blind controlled studies have proved that QSYQ has similar efficacy as enteric coated aspirin in the secondary prevention of myocardial infarction. AIM OF STUDY: The aim of study was to explore the effect of QSYQ on reverse cholesterol transport (RCT) pathway during atherosclerosis. MATERIALS AND METHODS: Eight-week-old male apoE-/- mice (on the gene background of C57BL/6J) were fed with a high-fat western diet and treated with low dose and high dose of QSYQ, as well as the positive control agent, liver X receptor-α (LXR-α) agonist GW3965. Eight weeks later, mice were sacrificed and the aorta was collected for atherosclerotic analysis. The aortic root was stained with Oil red O to evaluate the area of atherosclerotic lesion, and stained with immunohistochemistry to analyze the intra-plaque component and RCT protein in atherosclerotic plaque. The thoracic aorta was used to detect differentially expressed genes by comparative transcriptome RNA-seq and the protein expression of RCT pathway by western blotting. RESULTS: After eight weeks of treatment, we found that both of QSYQ and LXR-α agonist reduced atherosclerotic plaque area significantly, and decreased the intra-plaque component, including the lipid, the smooth muscle cell and the macrophage. Compared with the control group, there were 49 differentially expressed genes in low-dose QSYQ group, including 21 up-regulated genes and 28 down-regulated genes. The results of GO and KEGG analysis showed that the differentially expressed genes mainly concentrated in the negative regulation of lipid biosynthesis, positive regulation of lipid metabolism, cell response to lipids, negative regulation of lipid storage, fatty acid degradation, and glycerol ester metabolism. Both of QSYQ and LXR-α agonist reduced the protein expression of CD36 and increased the protein expression of PPARγ-LXRα/ß-ABCA1 in atherosclerotic plaque. CONCLUSION: The anti-atherosclerotic mechanism of QSYQ was involved in inhibiting lipid phagocytosis and promoting reverse cholesterol transport, therefore reducing lipid deposition and inflammatory cells in plaque.

Effects of ozone combined with articular injection of sodium hyaluronate on patients with knee osteoarthritis and their inflammatory factors and hemorheological indices.

Objective: Knee osteoarthritis (KOA) is a common chronic progressive disease. We aimed to evaluate the effects of ozone combined with articular injection of sodium hyaluronate on KOA patients and their inflammatory factors and hemorheological indices. Methods: A total of 292 KOA patients treated from October 2020 to October 2021 were randomly divided into observation and control groups (n=146). Observation group was treated with ozone combined with articular injection of sodium hyaluronate, while control group was routinely given glucosamine hydrochloride tablets and articular injection of sodium hyaluronate. The treatment was performed once a week for 5 consecutive weeks. Their general data, treatment outcomes, visual analogue scale (VAS) score, Hospital for Special Surgery (HSS) knee score, inflammatory factor levels and hemorheological indices were compared. Results: After treatment, observation group had significantly lower VAS score and higher HSS score than those of control group (P<0.05). The total response rate of observation group was higher than that of control group (P<0.05). The levels of inflammatory factors in the joint fluid were significantly lower in observation group than those in control group (P<0.05). The hemorheological indices were improved in both groups, especially in observation group (P<0.05). Conclusion: Ozone combined with articular injection of sodium hyaluronate has obvious therapeutic effects on KOA.

A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rapidly spreading worldwide. Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections. However, the emergence of SARS-CoV-2 variants of concern (VOCs), such as Delta (B.1.617.2) and the recently emerged Omicron (B.1.1.529), has seriously challenged the application of current therapeutics. Therefore, there is still a pressing need for identification of new broad-spectrum antivirals. Here, we further characterized a human antibody (58G6), which we previously isolated from a patient, with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations (IC50) of 1.69 ng/ml and 54.31 ng/ml, respectively. 58G6 shows prophylactic and therapeutic efficacy in hamsters challenged with the Delta and Omicron variants through nasal delivery. Notably, a very low dosage (2 mg/kg daily) of 58G6 efficiently prevented Omicron variant replication in the lungs. These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection. In general, 58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants. To the best of our knowledge, 58G6 is one of the most potent neutralizing antibodies against Omicron, with a broader spectrum than those approved for clinical use. 58G6 could be developed as a nebulized therapy, which would be more cost effective and user friendly and enhance the clinical outcome compared to that obtained with direct nasal delivery.

Ir(III)-catalyzed quadruple C-H activation of N-arylimidazolium and diaryliodonium salts: facile access to polysubstituted imidazo[1,2-f]phenanthridiniums.

Herein, N-heterocyclic carbene-directed Ir(III)-catalyzed cascade C-H arylation/annulation of N-arylimidazolium with diaryliodonium salts has been accomplished for the first time via a quadruple C-H activation strategy to construct imidazo[1,2-f]phenanthridinium structures. This protocol overcomes the compatibility of three kinds of different C-H activations with high catalytic efficiency, which allows ortho-unhindered N-arylimidazoliums to undergo a diarylation/annulation reaction, affording a variety of polysubstituted imidazo[1,2-f]phenanthridiniums. Neutral imidazo[1,2-f]phenanthridines are also prepared via a demethylation reaction of imidazo[1,2-f]phenanthridiniums.

Rh(III)-catalysed C-H/C-H cross-coupling of S-aryl sulfoximines with thiophenes: facile access to [1]benzothieno[3,2-b][1]benzothiophene (BTBT) and benzothiazines.

Reported herein is rhodium-catalysed oxidative C-H/C-H cross-coupling of S-aryl sulfoximines with thiophenes via a chelation-assisted strategy, which provides an efficient approach for the construction of [1]benzothieno[3,2-b][1]benzothiophene (BTBT) and benzothiazine skeletons from easily available substrates. This protocol exhibits a good compatibility with halogen substituents, thus paving the way for further transformation to prepare various organic functional molecules. The resulting benzothiazine derivative shows a deep blue emission with Commission Internationale de 'Eclairage (CIE) coordinates of (0.15, 0.04), a high quantum yield, and a delayed fluorescence lifetime.

Phase-Controlled Synthesis of Pd-Se Nanocrystals for Phase-Dependent Oxygen Reduction Catalysis.

Searching for highly efficient oxygen reduction reaction (ORR) electrocatalysts for fuel cell technology, in which the crystal structure plays a powerful role in regulating the electrocatalysis, is urgent yet challenging. Herein, we have explored the active and stable Pd-Se alloy electrocatalysts with controlled phase toward alkaline ORR. The phase-controlled Pd-Se nanoparticles (NPs) show interesting phase-dependent electrocatalytic performance, in which the Pd17Se15 NPs/C exhibits much better ORR performance than its counterpart, Pd7Se4 NPs/C, and the commercial Pd/C and Pt/C. Based on the detailed analysis, Pd in Pd17Se15 possesses more Se atom coordination and a higher valence state, thus providing a stronger capacity for the absorption of oxygenated species. DFT further reveals more charge transfer from the Pd17Se15 surface to the *OOH intermediate, which is the reason for the activity enhancement.

A Generalized Surface Chalcogenation Strategy for Boosting the Electrochemical N2 Fixation of Metal Nanocrystals.

Electrocatalytic nitrogen reduction reaction (NRR) is a promising process relative to energy-intensive Haber-Bosch process. While conventional electrocatalysts underperform with sluggish paths, achieving dissociation of N2 brings the key challenge for enhancing NRR. This study proposes an effective surface chalcogenation strategy to improve the NRR performance of pristine metal nanocrystals (NCs). Surprisingly, the NH3 yield and Faraday efficiency (FE) (175.6 ± 23.6 mg h-1 g-1 Rh and 13.3 ± 0.4%) of Rh-Se NCs is significantly enhanced by 16 and 15 times, respectively. Detailed investigations show that the superior activity and high FE are attributed to the effect of surface chalcogenation, which not only can decrease the apparent activation energy, but also inhibit the occurrence of the hydrogen evolution reaction (HER) process. Theoretical calculations reveal that the strong interface strain effect within core@shell system induces a critical redox inversion, resulting in a rather low valence state of Rh and Se surface sites. Such strong correlation indicates an efficient electron-transfer minimizing NRR barrier. Significantly, the surface chalcogenation strategy is general, which can extend to create other NRR metal electrocatalysts with enhanced performance. This strategy open a new avenue for future NH3 production for breakthrough in the bottleneck of NRR.

Verbascoside inhibits progression of glioblastoma cells by promoting Let-7g-5p and down-regulating HMGA2 via Wnt/beta-catenin signalling blockade.

Glioblastoma (GBM) continues to show a poor prognosis despite advances in diagnostic and therapeutic approaches. The discovery of reliable prognostic indicators may significantly improve treatment outcome of GBM. In this study, we aimed to explore the function of verbascoside (VB) in GBM and its effects on GBM cell biological processes via let-7g-5p and HMGA2. Differentially expressed GBM-related microRNAs (miRNAs) were initially screened. Different concentrations of VB were applied to U87 and U251 GBM cells, and 50 µmol/L of VB was selected for subsequent experiments. Cells were transfected with let-7g-5p inhibitor or mimic, and overexpression of HMGA2 or siRNA against HMGA2 was induced, followed by treatment with VB. The regulatory relationships between VB, let-7g-5p, HMGA2 and Wnt/ß-catenin signalling pathway were determined. The results showed that HMGA2 was a direct target gene of let-7g-5p. VB treatment or let-7g-5p overexpression inhibited HMGA2 expression and the activation of Wnt/ß-catenin signalling pathway, which further inhibited cell viability, invasion, migration, tumour growth and promoted GBM cell apoptosis and autophagy. On the contrary, HMGA2 overexpression promoted cell viability, invasion, migration, tumour growth while inhibiting GBM cell apoptosis and autophagy. We demonstrated that VB inhibits cell viability and promotes cell autophagy in GBM cells by up-regulating let-7g-5p and down-regulating HMGA2 via Wnt/ß-catenin signalling blockade.

Pd(II)-Catalyzed Regioselective Multiple C-H Arylations of 1-Naphthamides with Cyclic Diaryliodonium Salts: One-Step Access to [4]- and [5]Carbohelicenes.

Highly efficient and rapid construction of carbohelicenes is a desired but challenging task, especially starting from simple substrates. Herein, Pd(II)-catalyzed regioselective multiple C-H arylations of 1-naphthamides with cyclic diaryliodoniums have been accomplished for the first time, which enables facile one-step syntheses of [4]- and [5]carbohelicenes from readily available starting materials. The resulting single and double [4]carbohelicenes emit violet to deep-blue fluorescence; [4,5,4]-fused triple carbohelicenes exhibit sky-blue emissions, and phenoxazine-modified [4]carbohelicene shows a delayed fluorescence emission.

Differential Inhibition of Target Gene Expression by Human microRNAs.

microRNAs (miRNAs) exert their functions by repressing the expression of their target genes, but most miRNA target genes are unknown, and the degree to which a miRNA differentially inhibits the expression of its targets is underappreciated. We selected human miR-1, miR-122, and miR-124 as representatives to investigate the reliability of miRNA target predictions and examine how miRNAs suppress their targets. We constructed miRNA target gene reporter libraries based on prediction programs TargetScan, miRanda, and PicTar, and performed large-scale reporter assays to directly evaluate whether and how strongly a predicted target gene is repressed by its miRNA. We then performed statistical analyses to examine parameters that contributed to the miRNA inhibition of target genes. We found that the three programs have approximately 72-85% success rates in predicting genuine targets and that the miRNA inhibition of different targets varies in extent. We also identified parameters that could predict the degrees of miRNA repression, and further showed that differential miR-124 repression might contribute to differential gene expression in vivo. Our studies systematically investigated hundreds of miRNA target genes, shed light on factors influencing miRNA functions, and suggested a new mechanism by which differential target repression by miRNAs regulates endogenous gene expression.

Short- and long-term effects of manganese, zinc and copper ions on nitrogen removal in nitritation-anammox process.

This study provided a deep insight into the impacts of trace elements (Mn2+, Zn2+ and Cu2+) on nitritation-anammox process. For short-term exposure, all the three elements could improve the nitrogen removal rate (NRR) and the optimal concentrations were 2.0 mg/L, 2.0 mg/L and 0.5 mg/L for Mn2+, Zn2+ and Cu2+, respectively. Accordingly, the NRRs were enhanced 54.62%, 45.93% and 44.09%. The long-term experiments were carried out in lab-scale sequencing batch reactors. The surprising results showed that only Mn2+ addition could enhance the long-term nitritation-anammox process, and the NRR increased from 0.35 ± 0.01 kg N/m3/d (control, no extra trace element addition) to 0.49 ± 0.03 kg N/m3/d. Vice versa, the amendment of Zn2+ reduced the NRR to 0.28 ± 0.02 kg N/m3/d, and Cu2+ had no significant effect on the NRR (0.36 ± 0.01 kg N/m3/d). From the analysis of microbial community structure, it was explained by the increasing abundance of anaerobic ammonium oxidizing bacteria (AnAOB) only in Mn2+ treatment, whereas Zn2+ predominantly promoted ammonium oxidizing bacteria (AOB). Additionally, the majority of Mn2+ was identified inside AnAOB cells, and Zn2+ and Cu2+ were mainly located in AOB. Our results indicated the synergistic effects of trace elements on nitritation-anammox, both short-term encouraging activities of AnAOB and long-term altering microbial community structure. This work implies the importance of trace elements addition in nitritation-anammox process.

[Treatment of lesions in mesencephalic aqueduct and around it by neuroendoscope].

OBJECTIVE: To explore the surgical efficacy of lesions in mesencephalic aqueduct and around it with neuroendoscope. METHODS: A total of 14 cases with lesion underwent neuroendoscope. Endoscopic third ventriculostomy (ETV), excision or biopsy and mesencephalic aqueduct plasty were performed. RESULTS: There were primary obstruction (n = 4), glioma (n = 4), intraventricular cysticercosis (n = 2), pineal cell tumor (n = 1), lymphoma (n = 1), brain abscess (n = 1) and germinoma (n = 1). Postoperative cranial computed tomography (CT) and/or magnetic resonance imaging (MRI) showed narrowed ventricle. The outcomes were symptomatic improvement (n = 5), no change (n = 5), worsening (n = 4) and mortality (n = 0). CONCLUSION: ETV, lesion biopsy or partial lesion resection and aqueductal plasty are efficacious for the patients with lesions in mesencephalic aqueduct and around it.

[Surgical treatment of neuroendoscopy with supported channel for hypertensive intraventricular hemorrhage].

OBJECTIVE: To evaluate the value and efficacy of surgical treatment with neuroendoscopy with supported channel for hypertensive intraventricular hemorrhage (HIVH). METHODS: The clinical data of 32 patients with hypertensive intraventricular hemorrhage were retrospectively analyzed. And they underwent neuroendoscopy with supported channel. RESULTS: Computed tomography scans at Day 1 postoperation revealed that the evacuation of intraventricular hematoma was 85.4% in all patients. The Glasgow coma score (GCS) at Week 1 postoperation was significantly higher than that at preoperation. The postoperative outcomes were intracranial infection (n = 1), mortality (n = 1) and secondary hemorrhage (n = 3). All patients were followed up for 3 months. According to Glasgow outcome scale (GOS), there were excellent recovery (n = 17), moderate disability (n = 7), severe disability (n = 5) and vegetative survival (n = 3). CONCLUSION: The surgical treatment of neuroendoscopy with supported channel for HIVH offers great advantages with a low rate of complications and favorable outcomes.

Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.

BACKGROUND: Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot-Marie-Tooth disease. METHODS: We identified a family with a recessive form of Charcot-Marie-Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members. RESULTS: We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot-Marie-Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome. CONCLUSIONS: As shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients.

[Treatment of lumbar intervertebral disc herniation accompanying with lumbar instability with internal fixation and spinal fusion].

OBJECTIVE: To explore operative effect of lumbar intervertebral disc herniation accompanying with lumbar instability. METHODS: Form June 2000 to June 2006, 46 patients of lumbar intervertebral disc herniation accompanying with lumbar instability were treated with decompression through posterior approach, diskectomy, spinal fusion and vertebral pedicle internal fixation. Including 33 males and 13 females,the age was from 37 to 68 years with an average of 48 years. The course of disease was from 4 months to 20 years with an average of 3.5 years. There were simple segment in 21 cases, double segments in 22 cases, three segments in 3 cases. RESULTS: All patients were followed up for 12-45 months with an average of 25 months. All cases got solid fusion and clinical symptom improved obviously. According to clinical standard to evaluation, 32 cases obtained excellent result, 8 good, 6 fair. The rate of excellent and good was 86.9%. CONCLUSION: Diskectomy, spinal fusion and internal fixation can obtain satisfactory clinical effect for lumbar intervertebral disc herniation accompanying with lumbar instability.

[Aerobic nitrifying granulation fed with source-separated urine in sequencing batch reactor].

Morphological characteristics of aerobic nitrifying granules that were utilized to treat the diluted source-separated urine were investigated in two lab-scale sequencing batch reactors. In the first sequencing batch reactor, which was inoculated with nitrifying bacteria, the COD of effluent was markedly decreased while the nitrification rate was very low. Aerobic nitrifying granules were not appeared in the first bioreactor. In the other SBR system that was inoculated with aerobic granules cultivated in the laboratory, the COD and ammonia in source-separated urine were effectively removed and the removal rate was more than 90%. Under operational condition that influent ammonia volume rate was 0.5 kg/(m3 x d) for 70 days, the aerobic nitrifying granules were stable in the reactor. Aerobic nitrifying granules have well settleability and metabolize activity, the surface of granules was occupied by nitrifying bacillus and cocci bacteria. Contrast to the inoculating aerobic granules, the diameter of aerobic nitrifying granules dramatically decreased to more than 2 mm and the settle velocity were greater than that of aerobic granules which have the same diameter.