Altered leptin level in autism spectrum disorder and meta-analysis of adipokines.

BACKGROUND: Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis. METHODS: Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies. RESULTS: Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis. CONCLUSIONS: These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.

Rational reformation of Corynebacterium glutamicum for producing L-lysine by one-step fermentation from raw corn starch.

This article focuses on engineering Corynebacterium glutamicum to produce L-lysine efficiently from starch using combined method of "classical breeding" and "genome breeding." Firstly, a thermo-tolerable L-lysine-producing C. glutamicum strain KT45-6 was obtained after multi-round of acclimatization at high temperature. Then, amylolytic enzymes were introduced into strain KT45-6, and the resultant strains could use starch for cell growth and L-lysine production except the strain with expression of isoamylase. In addition, co-expression of amylolytic enzymes showed a good performance in starch degradation, cell growth and L-lysine production, especially co-expression of α-amylase (AA) and glucoamylase (GA). Moreover, L-lysine yield was increased by introducing AA-GA fusion protein (i.e., strain KT45-6S-5), and finally reached to 23.9 ± 2.3 g/L in CgXIIIPM-medium. It is the first report of an engineered L-lysine-producing strain with maximum starch utilization that may be used as workhorse for producing amino acid using starch as the main feedstock. KEY POINTS: • Thermo-tolerable C. glutamicum was obtained by temperature-induced adaptive evolution. • The fusion order between AA and GA affects the utilization efficiency of starch. • C. glutamicum with starch utilization was constructed by optimizing amylases expression.

LINC00536 promotes hepatocellular carcinoma progression via the miR-203b-5p/VEGFA axis.

LncRNAs exert comprehensive effects in regulating the initiation and deterioration of hepatocellular carcinoma (HCC). However, the specific expression profiles and functional mechanisms of LINC00536 in HCC need to be disclosed. The study is intended to clarify the leverage of LINC00536 in HCC and investigate the potential mechanisms for the regulatory role of LINC00536 in the progression of HCC. In our study, LINC00536 was overexpressed in tumor samples of HCC patients and was related to poor prognosis. LINC00536 knockdown impaired cell viability, proliferation, migration, and invasion. LINC00536 can directly bind with miR-203b-5p, trimming the miR-203b-5p expression levels. VEGFA designates as a target of miR-203b-5p. Rescue research indicated that the miR-203b-5p inhibition or VEGFA overexpression could reverse the impaired cell phenotypes induced by LINC00536 knockdown. The in vivo experiments upheld the LINC00536/miR-203b-5p/VEGFA axis in HCC. Conclusively, LINC00536 could promote HCC deterioration via tuning the miR-203b-5p/VEGFA axis. This research may provide theoretical evidence for LINC00536 to get a gratifying therapeutic target for HCC.

Evaluation of the "safe multidisciplinary app-assisted remote patient-self-testing (SMART) model" for warfarin home management during the COVID-19 pandemic: study protocol of a multi-center randomized controlled trial.

BACKGROUND: Warfarin treatment requires frequent monitoring of INR (international normalized ratio) to adjust dosage in a therapeutic range. In China, patients living in small towns usually go to tertiary hospitals to get warfarin monitoring and dosing, resulting in low frequencies of follow-ups and high incidence of complications. Influenced by the COVID-19 pandemic, patients on warfarin have further reduced their visits to healthcare institutions. While patient self-testing (PST) via using a point-of-care testing device for INR measuring at home has been widely used in developed countries and demonstrated improved clinical outcomes compared to usual care in clinics, it is rarely applied in developing countries, including China. This proposed study will develop and assess the "Safe Multidisciplinary App-assisted Remote patient-self-Testing (SMART) model" for warfarin home management in China during the COVID-19 pandemic. METHODS: This is a multi-center randomized controlled trial. We will carry out the study in three county hospitals, three small tertiary hospitals and three large tertiary hospitals with anticoagulation clinics in Hunan province of China. Eligible patients will be randomly assigned to the SMART model group (n = 360) or the control group (usual care clinic group, n = 360; anticoagulation clinic group, n = 120). Patients in the SMART model group do PST at home once every two to 4 weeks. Controls receive usual care in the clinics. All the patients will be followed up through outpatient clinics, phone call or online interviews at the 3rd, 6th, 9th and 12th month. The percentage of time in therapeutic range (TTR), incidence of warfarin associated major bleeding and thromboembolic events and costs will be compared between the SMART model group and control groups. DISCUSSION: Patients in the SMART model group would show improved TTR, lower incidence of complications and better quality of life compared to the control groups. Our design, implementation and usage of the SMART model will provide experience and evidence in developing a novel model for chronic disease management to solve the problem of healthcare service maldistribution, an issue particularly obvious in developing countries during the COVID-19 pandemic. TRIAL REGISTRATION: ChiCTR, ChiCTR 2000038984 . Registered 11 October, 2020.

[Correlation of gut microbiota and ischemic stroke: a review].

With the widespread application of next-generation sequencing(NGS), especially 16 S rRNA and shotgun sequencing, researchers are no longer troubled with massive data on the gut microbiota, and the correlation between the gut microbiota and the brain(central nervous system) has been gradually revealed. Research on the microbiota-gut-brain axis(MGBA) based on the gut microbiota have provided insights into the exploration of the pathogenesis and risk factors of ischemic stroke(IS), a cerebrovascular disease with high disability and mortality rates, and also facilitate the selection of therapeutic targets of this class of drugs. This study reviewed the application of NGS in the study of gut microbiota and the research progress of MGBA in recent years and systematically collated the research papers on the correlation between IS and gut microbiota. Furthermore, from the bi-directional regulation of MGBA, this study also discussed the high-risk factors of IS under the dysregulation of gut microbiota and the pathophysiological changes of gut microbiota after the occurrence of IS and summarized the related targets to provide a reliable reference for the therapeutic research of IS from the gut microbiota.

Metabolic engineering of carbohydrate metabolism systems in Corynebacterium glutamicum for improving the efficiency of L-lysine production from mixed sugar.

The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of L-lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from Clostridium acetobutylicum. L-lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTSGlc and PTSFru) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and L-lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered C. glutamicum strain K-8 capable of producing 221.3 ± 17.6 g/L L-lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of L-lysine production from mixed sugar. This is also the first report for improving the efficiency of L-lysine production by systematic modification of carbohydrate metabolism systems.

Metabolic engineering of glucose uptake systems in Corynebacterium glutamicum for improving the efficiency of L-lysine production.

Traditional amino acid producers typically exhibit the low glucose uptake rate and growth deficiency, resulting in a long fermentation time because of the accumulation of side mutations in breeding of strains. In this study, we demonstrate that the efficiency of L-lysine production in traditional L-lysine producer Corynebacterium glutamicum ZL-9 can be improved by rationally engineering glucose uptake systems. To do this, different bypasses for glucose uptake were investigated to reveal the best glucose uptake system for L-lysine production in traditional L-lysine producer. This study showed that overexpression of the key genes in PTSGlc or non-PTSGlc increased the glucose consumption, growth rate, and L-lysine production. However, increasing the function of PTSGlc in glucose uptake led to the increase of by-products, especially for plasmid-mediated expression system. Increasing the participation of non-PTSGlc in glucose utilization showed the best glucose uptake system for L-lysine production. The final strain ZL-92 with increasing the expression level of iolT1, iolT2 and ppgK could produce 201.6 ± 13.8 g/L of L-lysine with a productivity of 5.04 g/L/h and carbon yield of 0.65 g/(g glucose) in fed-batch culture. This is the first report of a rational modification of glucose uptake systems that improve the efficiency of L-lysine production through increasing the participation of non-PTSGlc in glucose utilization in traditional L-lysine producer. Similar strategies can be also used for producing other amino acids or their derivatives.

Improvement of l-Leucine Production in Corynebacterium glutamicum by Altering the Redox Flux.

The production of l-leucine was improved by the disruption of ltbR encoding transcriptional regulator and overexpression of the key genes (leuAilvBNCE) of the l-leucine biosynthesis pathway in Corynebacterium glutamicum XQ-9. In order to improve l-leucine production, we rationally engineered C. glutamicum to enhance l-leucine production, by improving the redox flux. On the basis of this, we manipulated the redox state of the cells by mutating the coenzyme-binding domains of acetohydroxyacid isomeroreductase encoded by ilvC, inserting NAD-specific leucine dehydrogenase, encoded by leuDH from Lysinibacillus sphaericus, and glutamate dehydrogenase encoded by rocG from Bacillus subtilis, instead of endogenous branched-chain amino acid transaminase and glutamate dehydrogenase, respectively. The yield of l-leucine reached 22.62 ± 0.17 g·L-1 by strain ΔLtbR-acetohydroxyacid isomeroreductase (AHAIR)M/ABNCME, and the concentrations of the by-products (l-valine and l-alanine) increased, compared to the strain ΔLtbR/ABNCE. Strain ΔLtbR-AHAIRMLeuDH/ABNCMLDH accumulated 22.87±0.31 g·L-1 l-leucine, but showed a drastically low l-valine accumulation (from 8.06 ± 0.35 g·L-1 to 2.72 ± 0.11 g·L-1), in comparison to strain ΔLtbR-AHAIRM/ABNCME, which indicated that LeuDH has much specificity for l-leucine synthesis but not for l-valine synthesis. Subsequently, the resultant strain ΔLtbR-AHAIRMLeuDHRocG/ABNCMLDH accumulated 23.31 ± 0.24 g·L-1 l-leucine with a glucose conversion efficiency of 0.191 g·g-1.

Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase to switch the nucleotide-cofactor specificity for increasing l-lysine production.

l-lysine is an important amino acid in animals and humans and NADPH is a vital cofactor for maximizing the efficiency of l-lysine fermentation. Dihydrodipicolinate reductase (DHDPR), an NAD(P)H-dependent enzyme, shows a variance in nucleotide-cofactor affinity in bacteria. In this study, we rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its nucleotide-cofactor specificity resulting in an increase in final titer (from 82.6 to 117.3 g L-1 ), carbon yield (from 0.35 to 0.44 g [g glucose]-1 ) and productivity (from 2.07 to 2.93 g L-1 hr-1 ) of l-lysine in JL-6 ΔdapB::Ec-dapBC115G,G116C in fed-batch fermentation. To do this, we comparatively analyzed the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating that hetero-expression of NADH-dependent EcDHDPR increased l-lysine production. Subsequently, we rationally modified the conserved structure of cofactor-binding motif, and results indicated that introducing the mutation K11A or R13A in CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the nucleotide-cofactor affinity of DHDPR. Lastly, the effects of these mutated DHDPRs on l-lysine production were investigated. The highest increase (26.2%) in l-lysine production was observed for JL-6 ΔdapB::Ec-dapBC115G,G116C , followed by JL-6 Cg-dapBC37G,G38C (21.4%) and JL-6 ΔdapB::Ec-dapBC46G,G47C (15.2%). This is the first report of a rational modification of DHDPR that enhances the l-lysine production and yield through the modulation of nucleotide-cofactor specificity.

[Highly Efficient Bilayer-Structure Yellow-Green OLED with MADN Hole-Transport Layer and the Impedance Spectroscopy Analysis].

Abstract Highly efficient bilayer-structure yellow-green organic light-emitting device (OLED) has been demonstrated based on MADN as hole-transport layer (HTL) and host-guest coped system of [Alq3: 0.7 Wt% rubrene] as emitting and electron-trans- port layer. The device gives yellow-green emission through incomplete energy transfer from the host of Alq3 to the guest of ru- brene. An electroluminescent peak of 560 nm, 1931 CIE color coordinates of (0.46, 0.52) and a maximum current efficiency of 7.63 cd · A⁻¹ (which has been enhanced by 30% in comparison with the counterpart having conventional NPB HTL) are ob- served. The hole-transporting characteristics of MADN and NPB have been systematically investigated by constructing hole-only devices and employing impedance spectroscopy analysis. Our results indicate that MADN can be served as an effective hole-trans- port material and its hole-transporting ability is slightly inferior to NPB. This overcomes the shortcoming of hole transporting more quickly than electron in OLED and improves carrier balance in the emitting layer. Consequently, the device current efficien- cy is promoted. In addition, the current efficiency of bilayer-structure OLED with MADN as HTL is comparable to that of conv- entinol trilayer-structure device with MADN as HTL and Alq3 as electron-transport layer. This indicates that the simplified bi- layer-structure device can be achieved without sacrificing current efficiency. The emitting layer of [Alq: 0.7 Wt% rubrene possesses superior elecron-transporting ability.

Clinical and radiographic outcomes of dynamic cervical implant replacement for treatment of single-level degenerative cervical disc disease: a 24-month follow-up.

PURPOSE: To determine the role of dynamic cervical implant (DCI) replacement for single-level degenerative cervical disc disease in Chinese patients. METHODS: Thirty patients with single-level degenerative cervical disc disease were prospectively enrolled between April 2010 and August 2010 (12 women, 18 men; mean age 56.5 years). All patients underwent anterior cervical decompression, DCI replacement, clinical and radiological assessments preoperatively and at 1, 6, 12, and 24 months postoperatively, and Japanese Orthopaedic Association (JOA), Visual Analogue Scale (VAS), Neck Disability Index (NDI), and Short Form 36 (SF-36) scores. Lateral neutral radiographs provided the intervertebral space height. Lateral dynamic radiographs were taken to measure the range of motion (ROM) of the cervical spine and functional spinal unit (FSU) of the treated segment. We compared the amount of motion of the adjacent vertebral endplate and the intrinsic motion of the implant and calculated a correlation analysis. RESULTS: DCI showed good clinical and radiographic outcomes. At the final follow-up, JOA, VAS, NDI, and SF-36 average scores improved significantly. The intervertebral space height increased slightly after operation and was maintained during follow up. The ROM of the cervical spine and FSU decreased at early follow-up, but recovered to the preoperative level within 1-2 years. There was a high index of linear correlation between the motion of the adjacent vertebral endplate and the intrinsic motion of the implant. CONCLUSIONS: DCI provided elastic dynamic stability for the targeted segment, and restored and sustained intervertebral space height and ROM of the cervical spine.

Design, Synthesis, and Biological Activity of Novel Triketone-Containing Phenoxy Nicotinyl Inhibitors of HPPD.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.

Cytochrome P450 oxidoreductase genetic polymorphisms A503V and rs2868177 do not significantly affect warfarin stable dosage in Han-Chinese patients with mechanical heart valve replacement.

PURPOSE: To investigate the influence of cytochrome P450 oxidoreductase (POR) polymorphisms (A503V and rs2868177) on warfarin stable dosage (WSD) in Han-Chinese patients with mechanical heart valve replacement (MHVR). METHODS: Three hundred and seventeen Han-Chinese MHVR patients on stable maintenance dose of warfarin were enrolled. Blood samples were collected for genotyping analyses of VKORC1 -1639G>A, CYP2C9 *3, CYP4F2 rs2108622 and POR (A503V and rs2868177). Average WSD of carriers with variant POR genotypes or haplotypes were compared. Association analyses were performed by single and multiple linear regression analysis. RESULTS: The variant allele frequencies of POR polymorphisms (A503V and rs2868177) were 38.8 % and 44.8 %, respectively. D' between POR A503V and rs2868177 was 0.855, r(2) was 0.375, and the frequencies of the four POR haplotypes were 42.3 % for CG, 36.3 % for TA, 18.9 % for CA, and 2.5 % for TG, respectively. There were no significant differences in average WSD among carriers with three variant POR A503V genotypes or among carriers with three variant POR rs2868177 genotypes (both P > 0.05). Similarly, there were no significant differences in average WSD among carriers with variant POR haplotypes (all P > 0.05). Neither single nor multiple linear regression analyses showed significant effects of POR A503V or POR rs2868177 polymorphisms on WSD. CONCLUSION: POR polymorphisms (A503V and rs2868177) do not appear to significantly influence WSD in Han-Chinese patients with MHVR.

Salmonella typhimurium mediated delivery of Apoptin in human laryngeal cancer.

An effective cancer therapeutic should target tumours specifically with limited systemic toxicity. Here, we transformed an attenuated Salmonella typhimurium (S. typhimurium) with an Apoptin expressing plasmid into a human laryngeal carcinoma cell line. The expression of the inserted gene was measured using fluorescence and immunoblotting assays. The attenuated S. typhimurium-mediated Apoptin significantly decreased cytotoxicity and strongly increased cell apoptosis through the activation of caspase-3. The process was mediated by Bax, cytochrome c and caspase-9. A syngeneic nude murine tumour model was used to determine the anti-tumour effects of the recombinant bacteria in vivo. Systemic injection of the recombinant bacteria with and without re-dosing caused significant tumour growth delay and reduced tumour microvessel density, thereby extending host survival. Our findings indicated that the use of recombinant Salmonella typhimurium as an Apoptin expression vector has potential cancer therapeutic benefits.

Hip Pain after Distal Femoral Derotational Osteotomy for a Patient with Patellar Instability: A Case Report.

BACKGROUND: Increased torsional deformity of femur is one of the most important factors in recurrent patellofemoral instability. And distal femoral derotational osteotomy is an effective treatment option in patients with increased femoral torsional deformity. However, groin pain is a rare complication after femoral derotational osteotomy. CASE PRESENTATION: The patient was a 23-year-old female suffering from anterior knee pain and patellar instability in her left leg. Continuous CT scans of the hip, knee, and ankle were performed and the femoral anteversion was 44.99°. Considering the significant enlargement of the femoral internal torsion which may contribute most for dislocation of patella, we did a derotational osteotomy of distal femur. The anterior knee pain and patellar instability were resolved after surgery. The femoral internal torsion angle was corrected to 21.47°. But she developed left hip pain in the groin area which she had never encountered before 1 year after the surgery. We believed that the hip pain was closely related to the surgery. And the imaging and follow-up partly confirmed this. CONCLUSIONS: The situation of the hip joint should be carefully evaluated before doing derotational osteotomy in recurrent patellofemoral instability and patient should be informed that derotational osteotomy may cause hip pain. Clinical studies are needed to further clarify the impact of derotational osteotomy on the hip.

Enhancement of the Josephson Current in a Quantum Dot Connected to Majorana Nanowires.

We investigate the behavior of the Josephson current in a system composed of a quantum dot (QD) sandwiched between two nanowires by using the nonequilibrium Green's function technique. We consider that the nanowires are in proximity to s-wave superconducror substrates, and Majorana bound states (MBSs) are induced at their ends. It is also assumed that the two nanowires are not aligned in the same orientation, but form a bent angle with respect to each other. It is found that when only one spin state on the QD is coupled to the left nanowire, the Josephson current is the typical sinusoidal function of the phase difference between the two nanowires. If both spin states hybridize to the MBSs with equal coupling strengths, the Josephson current then is not a sinusoidal function of the phase difference. In particular, when the bent angle between the two nanowires is π/2 and the two modes of the MBSs in each nanowire are decoupled from each other, the Josephson current is enhanced by about twenty times in magnitude as compared to the former case. Moreover, the simultaneously enhanced currents of the two spin directions are of the same magnitude but flow in opposite directions and they induce a large pure spin current. Our results also show that this abnormally enhanced Josephson current will be suppressed by a vertical magnetic field applied to the QD.

[Distribution, Respiratory Exposure, and Traceability of Atmospheric Microplastics in Yichang City].

As an emerging environmental pollutant, microplastics have attracted much attention, but the sources and health hazards of atmospheric microplastics (AMPs) remain unclear. In order to explore the distribution characteristics, assess the risk of human respiratory exposure, and analyze the sources of AMPs in different functional areas of Yichang City, AMPs samples from 16 observation points were collected and analyzed, and the HYSPLIT model was used. The results showed that the main shapes of AMPs in Yichang City were fiber, fragment, and film, and six colors were observed including transparent, red, black, green, yellow, and purple. The smallest size was 10.42 µm, and the largest was 4761.42 µm. The deposition flux of AMPs was (4400±474) n·(m2·d)-1. The types of APMs were polyester fiber (PET), acrylonitrile-butadiene-styrene copolymer (ABS), polyamide (PA), rubber (Rubber), polyethylene (PE), cellulose acetate (CA), and polyacrylonitrile (PAN). The order of the subsidence flux in each functional area was as follows:urban residential area>agricultural production area>landfill>chemical industrial park>town residential area. The human respiratory exposure risk assessment models showed that the daily intake of AMPs (EDI) for adults and children in urban residential areas was higher than in town residential areas. The atmospheric backward trajectory simulation showed that the AMPs in the districts and counties of Yichang City mainly came from the surrounding areas via short-distance transportation. This study provided basic data support for the research on AMPs in the middle reaches of the Yangtze River and was of great significance for the traceability and health risk research of AMPs pollution.

Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis.

BACKGROUND: Elderly rheumatoid arthritis (ERA) population faces multiple treatment dilemma. Here we aim to investigate if Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) exhibit better effects in an ERA mice model. METHODS: ERA mice model was established by adding D-galactose (Dgal) to collagen-induced arthritis (CIA) mice. The model was then assigned into control group (CIA + Dgal), MTX treatment group (MTX), GCNY treatment group (GCNY), and integrative treatment group (MTX + GCNY). Pathological scoring was performed to evaluate the severity between the groups. Proteomic analysis was applied to investigate the secretory phenotype of the ERA mouse model and the underlying mechanism of GCNY, MTX and their combination. Representative cytokines related to proteomic results were further validated by ELISAs. RESULTS: CIA + Dgal mice showed more aggressive joints damage than the CIA mice. Besides changes in the inflammatory pathway such as Pi3k-Akt signaling pathway in both model, differential expressed proteins (DEPs) indicated metabolism-related pathways were more obvious in CIA + Dgal mice. Low-dose MTX failed to show pathological improvement in CIA + Dgal mice, while GCNY improved joints damage significantly. Besides down-regulated inflammation-related targets, GCNY-regulated DEPs (such as Apoc1 ~ 3, Grk2 and Creb3l3) were broadly enriched in metabolism-related pathways. MTX + GCNY showed the best therapeutic effect, and the DEPs enriched in a variety of inflammatory,metabolism and osteoclast differentiation signaling pathway. Notably, MTX + GCNY treatment up-regulated Dhfr, Cbr1, Shmt1 involved in folic acid biosynthesis and anti-folate resistance pathways indicated a coincidence synergic action. ELISAs confirmed CPR and Akt that elevated in CIA + Dgal mice were significantly ameliorated by treatments, and adding on GCNY elevated folic acid levels and its regulator Dhfr. CONCLUSION: Aging aggravated joints damage in CIA, which probably due to metabolic changes rather than more severe inflammation. GCNY showed significant effects in the ERA mice model especially when integrated with MTX to obtain a synergic action.

[Clinical application of MC + PEEK cage in traumatic cervical disc herniation].

OBJECTIVE: To explore the clinical outcomes of surgical treatment for traumatic cervical disc herniation with MC + PEEK cage. METHODS: A total of 51 patients with traumatic cervical disc herniation in mono-segment were surgically treated. The patients in group A (n = 20) were treated by MC + PEEK cage while those in group B (n = 31) by anterior cervical plate with PEEK cage or titanium mesh. Various parameters of operative duration, blood loss volume, operative complications, bone union, height of intervertebral space and Japanese Orthopedic Association (JOA) score were recorded and compared. RESULTS: Fifty-one patients were followed up for an average time of 26 months (range: 6 - 40). Operative duration, blood loss volume and operative complications of group A were better than group B with statistical significance (P < 0.05). Bone union, height of intervertebral space and recovery of spinal cord function were satisfactory with no statistical difference (P > 0.05). CONCLUSION: With this new cage, traumatic cervical disc herniation may be safely and micro-invasively treated without the need of anterior cervical plate.

[Investigation of ophthalmic resources in Xinjiang Uyghur Autonomous Region in China].

OBJECTIVES: To explore ophthalmic resources and existing problems in Xinjiang Uyghur Autonomous Region, and to provide reasonable developing configuration for the future. METHODS: It was a population-based cross-section study. By using questionnaire to collect data from all eye units (national and private) which were registered in Xinjiang area. Investigation included: (1) ophthalmic medical unit of name, structure type, departments constitute; (2) the ophthalmic medical work; (3) the number of ophthalmology health technicians and distribution; (4) ophthalmic devices usage; (5) carry out the problems and difficulties encountered in ophthalmic work. Descriptive statistic method was used to analyze the structure of ophthalmic material, the availability of resource, the medical institution of different regions and types. RESULTS: One hundred and thirty questionnaire were filled out and 110 questionnaire were recovery. There were 107 eye units, 1709 beds for ophthalmic, 1672 employees, including 525 doctors, the ratio of doctors and nurses was 1.0:1.3. And the ophthalmic resources mainly distributed in northern Tianshan, very few in the eastern area in Xinjiang; ophthalmic units were denser in general hospitals which were above the county level. There were 43 580 ophthalmic surgeries in all, the main eye operation carried out was cataract surgery, including 20 303 (counted 46.59%) cataract operation. CONCLUSIONS: The ophthalmic units distribution is unbalanced, which is short of ophthalmologists. It provides base for government to arrange ophthalmic resources reasonably, to enhance the research motivation and to cultivate more professors, and to increase the number of ophthalmic specialists in the general hospitals, and eventually to maximize the benefit of ophthalmic service in Xinjiang.