Genetic analysis and QTL mapping for pericarp thickness in maize (Zea mays L.).

Proper pericarp thickness protects the maize kernel against pests and diseases, moreover, thinner pericarp improves the eating quality in fresh corn. In this study, we aimed to investigate the dynamic changes in maize pericarp during kernel development and identified the major quantitative trait loci (QTLs) for maize pericarp thickness. It was observed that maize pericarp thickness first increased and then decreased. During the growth and formation stages, the pericarp thickness gradually increased and reached the maximum, after which it gradually decreased and reached the minimum during maturity. To identify the QTLs for pericarp thickness, a BC4F4 population was constructed using maize inbred lines B73 (recurrent parent with thick pericarp) and Baimaya (donor parent with thin pericarp). In addition, a high-density genetic map was constructed using maize 10 K SNP microarray. A total of 17 QTLs related to pericarp thickness were identified in combination with the phenotypic data. The results revealed that the heritability of the thickness of upper germinal side of pericarp (UG) was 0.63. The major QTL controlling UG was qPT1-1, which was located on chromosome 1 (212,215,145-212,948,882). The heritability of the thickness of upper abgerminal side of pericarp (UA) was 0.70. The major QTL controlling UA was qPT2-1, which was located on chromosome 2 (2,550,197-14,732,993). In addition, a combination of functional annotation, DNA sequencing analysis and quantitative real-time PCR (qPCR) screened two candidate genes, Zm00001d001964 and Zm00001d002283, that could potentially control maize pericarp thickness. This study provides valuable insights into the improvement of maize pericarp thickness during breeding.

Purification and Structure Characterization of the Crude Polysaccharide from the Fruiting Bodies of Butyriboletus pseudospeciosus and Its Modulation Effects on Gut Microbiota.

Polysaccharides from the species of Boletaceae (Boletales, Agaricomycetes, Basidiomycota) are economically significant to both functional foods and medicinal industries. The crude polysaccharide from Butyriboletus pseudospeciosus (BPP) was prepared, and its physicochemical properties were characterized through the use of consecutive experimental apparatus, and its impact on the gut microbiota of Kunming mice was evaluated. Analyses of the structure characteristics revealed that BPP was mainly composed of Man, Glc, and Gal, possessing the pyranose ring and ß/α-glycosidic linkages. TG analysis exhibited that BPP had great heat stability. The SEM observation performed demonstrated that BPP appeared with a rough, dense, and porous shape. Through the BPP intervention, the serum and fecal biochemical index in mice can be improved obviously (p < 0.05). The abundance of beneficial microbiota in the BPP-treated group was significantly increased, while the abundance of harmful microbiota was significantly decreased (p < 0.05). Based on the Tax4Fun, we also revealed the relationship between the species of gut microbiota and showed that the high dose of BPP has significantly changed the functional diversities compared with those in other groups (p < 0.05). The results suggest that B. pseudospeciosus could serve as potential functional food or medicine.

Combined micro-apical surgery and vital pulp therapy in mandibular second molars with external root resorption caused by impacted teeth / 华西口腔医学杂志

OBJECTIVES@#This study aimed to establish a new treatment of the mandibular second molars with external root resorption caused by impacted teeth to preserve the affected teeth and their vital pulps.@*METHODS@#For mandibular second molars clinically diagnosed as external root resorption caused by impacted teeth, debridement and removal of the root at the resorption site via micro-apical surgery and direct capping of the pulp with bioactive material on the surface of the root amputation via vital pulp therapy were performed immediately after the impacted teeth were extracted.@*RESULTS@#The external root resorption of the affected tooth was ceased. It was asymptomatic with intact crown, normal pulp, periapical alveolar bone reconstruction, normal periodontal ligament, continuous bone sclerosis, and no periapical translucency in radiographic examination at the 1-year postoperative follow-up, thus showing good prognosis.@*CONCLUSIONS@#Simultaneous combination of micro-apical surgery and vital pulp therapy after extraction of impacted teeth could successfully preserve mandibular second molars with ERR caused by impacted teeth and their vital pulps.

Effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant in Guangdong Province / 中华预防医学杂志

Objective: To evaluate the effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant. Methods: A total of 1 403 Omicron-infected patients admitted to 20 designated hospitals in Guangdong Province from January 1 to May 31, 2022, were selected as subjects in this study. A case-control study was conducted to collect the demographic data, underlying disease, vaccination status, last exposure date, gene sequencing of infected strains and clinical outcomes from the China Disease Prevention and Control Information System and Guangdong telemedicine platform. Pneumonia (common, severe and critical) and non-pneumonia (asymptomatic and mild) were selected as the case group and control group. The effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant was analyzed. Results: The median age [M (Q1, Q3)] of the subjects was 36 (27-47) years old, with males accounting for 52.25% (733 cases). The main outcome of the infection was non-pneumonia, accounting for 92.09% (1 292 cases), and the duration [M (Q1, Q3)] of the disease was 18 (14-22) days. There were 134 (9.55%), 39 (2.78%), 403 (28.72%), 437 (31.15%) and 390 (27.80%) cases with no or partial vaccination, within 90 days of primary vaccination, over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination, respectively. Multivariate logistic regression analysis showed that after adjusting for gender, age, underlying disease, and location of the report, compared with those with no or partial vaccination, the risk of developing pneumonia was lower in those with over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination [OR (95%CI) values were 0.52 (0.28-0.98), 0.39 (0.21-0.73) and 0.40 (0.21-0.77), respectively]. Cox proportional hazard regression model analysis showed that after adjusting for gender, age, underlying disease and location of the report, the duration of the disease was shorter in those who received booster vaccinated for more than 90 days compared with that in those who had no or partial vaccination [HR (95%CI): 1.26 (1.03-1.55)]. Conclusion: The inactivated SARS-CoV-2 vaccine affects the clinical outcomes of patients infected with the Omicron variant.

Value for combination of T1WI star -VIBE with TWIST -VIBE dynamic contrast -enhanced MRI in distinguishing lung nodules / 中南大学学报(医学版)

OBJECTIVES@#With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T1 weighted free-breathing star-volumetric interpolated breath hold examination (T1WI star-VIBE) in identifying benign and malignant lung nodules.@*METHODS@#We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T1WI-VIBE, the contrast-enhanced T1WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared.@*RESULTS@#There were significant differences in unenhanced T1WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T1WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001).@*CONCLUSIONS@#T1WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.

Microstructure and Properties of Densified Gd2O3 Bulk.

In this work, Gd2O3 bulks were sintered at temperatures ranging from 1400 °C to 1600 °C for times from 6 h to 24 h, and their microstructure and properties were studied for a wider application of materials in thermal barrier coatings. The densification of the Gd2O3 bulk reached 96.16% when it was sintered at 1600 °C for 24 h. The elastic modulus, hardness, fracture toughness and thermal conductivity of the bulks all increased with the rise in sintering temperature and extension of sintering time, while the coefficient of thermal expansion decreased. When the Gd2O3 bulk was sintered at 1600 °C for 24 h, it had the greatest elastic modulus, hardness, fracture toughness and thermal conductivity of 201.15 GPa, 9.13 GPa, 15.03 MPa·m0.5 and 2.75 W/(m·k) (at 1100 °C), respectively, as well as the smallest thermal expansion coefficients of 6.69 × 10-6/°C (at 1100 °C).

Physiological and Molecular Characteristics of Southern Leaf Blight Resistance in Sweet Corn Inbred Lines.

Southern corn leaf blight is one of the most widespread foliar diseases in maize-producing areas worldwide and can seriously reduce the yield and quality of sweet corn. However, the molecular mechanisms underlying the disease in sweet corn have not been widely reported. In this study, two sweet corn inbred lines, resistant K13 (RK13) and susceptible K39 (SK39), were used to explore the disease resistance mechanism of southern leaf blight. We observed morphological characteristics and assessed the changes in protective enzymatic activity in sweet corn leaves after inoculation of C. heterostrophus. RNA-seq was performed to elucidate the transcriptional dynamics and reveal the key pathways involved in southern leaf blight resistance without pathogens (Mock) and at 1 and 3 days post inoculation (1 and 3 dpi). Differentially expressed genes (DEGs) were identified in the SK39 group (including three pairwise combinations: SK39-0d_vs_SK39-1d, SK39-1d_vs_SK39-3d and SK39-1d_vs_SK39-3d), the RK13 group (including three pairwise combinations: RK13-0d_vs_RK13-1d, RK13-1d_vs_RK13-3d and RK13-1d_vs_RK13-3d), and the SK39_vs_RK13 group (including three pairwise combinations: SK39-0d_vs_RK13-0d, SK39-1d_vs_RK13-1d, and SK39-3d_vs_RK13-3d). In our study, 9455 DEGs from the RK13 group, 9626 from the SK39 group, and 9051 DEGs from the SK39_vs_RK13 group were obtained. Furthermore, 2775, 163, and 185 DEGs were co-expressed at SK39_vs_RK13, RK13, and SK39, respectively. A functional analysis of the DEGs revealed that five pathways-i.e., photosynthesis, plant hormone signal transduction, MAPK signaling pathway, phenylpropanoid biosynthesis, and biosynthesis of secondary metabolites-and transcription factor families play crucial roles in disease resistance. The results from the present study enabled the identification of the JA and SA signaling pathways, which are potentially involved in the response to southern leaf blight in maize. Our findings also highlight the significance of ZIM transcription factors and pathogenesis-related (PR) genes during pathogen infection. This study preliminarily explored the molecular mechanisms of the interaction between sweet corn and C. heterostrophus and provides a reference for identifying southern leaf blight resistance genes in the future.

Integrative analysis of transcriptome and miRNAome reveals molecular mechanisms regulating pericarp thickness in sweet corn during kernel development.

Pericarp thickness affects the edible quality of sweet corn (Zea mays L. saccharata Sturt.). Therefore, breeding varieties with a thin pericarp is important for the quality breeding of sweet corn. However, the molecular mechanisms underlying the pericarp development remain largely unclear. We performed an integrative analysis of mRNA and miRNA sequencing to elucidate the genetic mechanism regulating pericarp thickness during kernel development (at 15 days, 19 days, and 23 days after pollination) of two sweet corn inbred lines with different pericarp thicknesses (M03, with a thinner pericarp and M08, with a thicker pericarp). A total of 2,443 and 1,409 differentially expressed genes (DEGs) were identified in M03 and M08, respectively. Our results indicate that phytohormone-mediated programmed cell death (PCD) may play a critical role in determining pericarp thickness in sweet corn. Auxin (AUX), gibberellin (GA), and brassinosteroid (BR) signal transduction may indirectly mediate PCD to regulate pericarp thickness in M03 (the thin pericarp variety). In contrast, abscisic acid (ABA), cytokinin (CK), and ethylene (ETH) signaling may be the key regulators of pericarp PCD in M08 (the thick pericarp variety). Furthermore, 110 differentially expressed microRNAs (DEMIs) and 478 differentially expressed target genes were identified. miRNA164-, miRNA167-, and miRNA156-mediated miRNA-mRNA pairs may participate in regulating pericarp thickness. The expression results of DEGs were validated by quantitative real-time PCR. These findings provide insights into the molecular mechanisms regulating pericarp thickness and propose the objective of breeding sweet corn varieties with a thin pericarp.

Traumatic superficial testicular dislocation and manual reduction guided by ultrasound: a case report / 中华泌尿外科杂志

Testicular dislocation is a rare clinical presentation that occurs most commonly as a result of blunt scrotal injury or abdominopelvic injury. In this study, a rare case of testicular dislocation was reported, who was a 65-year-old man presented with a right testicle squeezed into the subcutaneous penis, and a good recovery after a successful manual restoration under ultrasound guidance was achieved. The treatment of testicular dislocation is mostly surgical, but ultrasound-guided manual restoration may provide a feasible treatment for patients with superficial dislocation based on this case report.

Effect of Gd2O3 Addition on the Microstructure and Properties of Gd2O3-Yb2O3-Y2O3-ZrO2 (GYYZO) Ceramics.

Gd and Yb elements have high chemical stability, which can stabilize the solid solution in ZrO2. Gd2O3 and Yb2O3 have high melting points, and good oxidation resistance in extreme environments, stable chemical properties. Therefore, Gd2O3 and Yb2O3 were added to ZrO2 to stabilize oxides, improve the high temperature stability, and effectively decrease the thermal conductivity at high temperature. In this work, 5 wt% Yb2O3 and 5 wt%, 10 wt%, 15 wt% Gd2O3 were doped into 8 wt% Y2O3 stabilized ZrO2 (8YSZ) powders as thermal barrier coating materials, and sintered at 1650 °C for 6 h, 12 h, 24 h. The effects of Gd2O3 addition on the microstructure, density, thermal conductivity, hardness, and fracture toughness of Gd2O3-Yb2O3-Y2O3-ZrO2 (GYYZO) bulk composite ceramics were investigated. It was found that the densification of the 8YSZ bulk and GYYZO bulk with 15 wt% Gd2O3 reached 96.89% and 96.22% sintered at 1650 °C for 24 h. With the increase of Gd2O3 addition, the hardness, elastic modulus and fracture toughness of the GYYZO bulk increased and the thermal conductivity and thermal expansion coefficient of the GYYZO bulk decreased. GYYZO bulk with 15 wt% Gd2O3 sintered at 1650 °C for 24h had the highest hardness, elastic modulus and fracture toughness of 15.61 GPa, 306.88 GPa, 7.822 MPa·m0.5, and the lowest thermal conductivity and thermal expansion coefficient of 1.04 W/(m·k) and 7.89 × 10-6/°C at 1100 °C, respectively. The addition of Gd2O3 into YSZ could not only effectively reduce the thermal conductivity but also improve the mechanical properties, which would improve the thermal barrier coatings' performances further.

Comparative Transcriptome Analysis Reveals Regulatory Networks during the Maize Ear Shank Elongation Process.

In maize, the ear shank is a short branch that connects the ear to the stalk. The length of the ear shank mainly affects the transportation of photosynthetic products to the ear, and also influences the dehydration of the grain by adjusting the tightness of the husks. However, the molecular mechanisms of maize shank elongation have rarely been described. It has been reported that the maize ear shank length is a quantitative trait, but its genetic basis is still unclear. In this study, RNA-seq was performed to explore the transcriptional dynamics and determine the key genes involved in maize shank elongation at four different developmental stages. A total of 8145 differentially expressed genes (DEGs) were identified, including 729 transcription factors (TFs). Some important genes which participate in shank elongation were detected via function annotation and temporal expression pattern analyses, including genes related to signal transduction hormones (auxin, brassinosteroids, gibberellin, etc.), xyloglucan and xyloglucan xyloglucosyl transferase, and transcription factor families. The results provide insights into the genetic architecture of maize ear shanks and developing new varieties with ideal ear shank lengths, enabling adjustments for mechanized harvesting in the future.

Development of a nanobody-based immunoassay for the sensitive detection of fibrinogen-like protein 1.

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625-2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.

Preliminary study of fogging process for fixing high-concentration radioactive aerosol 131I contamination in a radiopharmaceutica production unit / 中国辐射卫生

Objective To prove the feasibility of a Fogging Process in fixing high-concentration radioactive aerosol 131I contamination. Methods High-concentration radioactive aerosol 131I contamination in an 131I-operating glovebox for radiopharmaceutical production was disposed by using fogging and fixing process. The aerosol 131I concentrations were detected and the results were analyzed. Results After a 120 minutes fixing, the 131I contamination in this glovebox reduced from(289 ± 9) DAC and (304 ± 6) DAC to (21.7 ± 2.0) DAC and (26.2 ± 1.8) DAC. After a 180 minutes fixing, the 131I contamination in this glovebox reduced from (259 ± 10) DAC to (1.80 ± 0.18) DAC. These results showed that no aerosol 131I contamination was raised again after 24-hours finishing this task. Conclusion Aerosol 131I concentration in a limited space could be controlled by using a fogging and fixing process, which could reduce the risk of internal exposure of staff. This process could be used by radiopharmaceutical production as an emergency management for dispose high-concentration radioactive aerosol 131I contamination.

Progress in clinical pharmacology of oligonucleotides / 药学学报

Following small molecules and monoclonal antibodies, oligonucleotides are expected to overcome the rare and refractory human diseases. It has been attracted the attention of the pharmaceutical industry since the approval of six oligonucleotides in recent years because of their unique mechanism of regulating disease gene transcription at the RNA level. As a new class of drug molecules, oligonucleotides are highly polar, charged, and need to be improved by means of chemical modification and drug delivery systems. And therefore, they have different clinical pharmacology properties compared with chemical molecules and monoclonal antibodies, which pose new challenges for early clinical development. This paper reviews the characteristics of oligonucleotides from the perspective of technological development, mechanism of action, human pharmacokinetics, efficacy and safety.

Evaluating the occupational exposure to hand-transmitted vibration in golf ball head grinding positions / 中国职业医学

OBJECTIVE: To evaluate the exposure status of hand-transmitted vibration(HTV)in golf ball head grinding workers.METHODS: The golf ball head grinding positions in a sports equipment factory were selected as the research subjects by the judgement sampling method.The HTV exposure level of the workers in 66 grinding positions was measured,the key control points for HTV hazards were identified,and the damage of HTV was classified.RESULTS: The median(M)of 4 hours energy equivalent frequency-weighted acceleration to vibration[a_(hw(4))]of grinding positions in this sports equipment factory was 4.21 m/s~2,and the a_(hw(4)) over standard rate was 50.0%(33/66).The a_(hw(4)) of rough grinding positions was higher than that of fine grinding positions(M:5.50 v.s 3.94 m/s~2,P<0.05).In both rough grinding positions and fine grinding positions,the a_(hw(4)) of different ball head grinding types from high to low were hollow titanium alloy ball heads, hollow stainless steel ball heads,and solid stainless steel ball heads(rough grinding positions M:7.41 vs4.43 vs 3.11 m/s~2,P<0.01; fine grinding p ositions M:5.24 vs 4.21 vs 2.93 m/s~2,P<0.01).For the hollow titanium alloy ball head grinding positions,the a_(hw(4)) of rough grinding was higher than that of fine grinding(M:7.47 vs 5.24 m/s~2,P<0.01).Rough grinding positions,especially hollow stainless steel ball heads and hollow titanium alloy ball head grinding positions were key control points for HTV hazards.In the 66 grinding positions,the HTV hazards were classified as grade 0,Ⅰ,Ⅱ,and Ⅲ in the grinding positions accounted for 3.0%,47.0%,40.9%,and 9.1%,respectively,and those with grade Ⅱ and above were 50.0%(33/66). CONCLUSION: The exposure level of HTV in golf ball head grinding workers is high,with a trend of exceeding the standard.The golf ball head grinding workers have a high occupational health risk.

Impact of levosimendan on cardiac function ,plasma BNP and serum cytokine levels in AHF patients／ / 心血管康复医学杂志

To observe therapeutic effect of levosimendan on acute heart failure (AHF) and its impact on cardiac function ,levels of brain natriuretic peptide (BNP) ,high sensitive C reactive protein (hsCRP) ,tumor necro‐sis factor (TNF)‐α and interleukin (IL)‐6. Methods :A total of 148 AHF patients treated in our hospital from Jan 2016 to Jan 2018 were randomly and equally divided into dobutamine group and levosimendan group ,both groups re‐ceived corresponding medication based on routine treatment for 21d.Cardiac function ,levels of plasma BNP ,serum hsCRP ,TNF‐α and IL‐6 ,6min walking distance (6MWD) before and after treatment ,total effective rate and inci‐dence of adverse reactions were observed and compared between two groups .Results :Total effective rate of levosi‐mendan group was significantly higher than that of dobutamine group (83. 78% vs.68.92%) , P＝0.033. Compared with dobutamine group after treatment , there were significant rise in LVEF [ (49. 98 ± 3. 68 )% vs.(52.17 ± 3.82)%] ,stroke volume [SV ,(67. 52 ± 5. 79) ml vs.(69. 48 ± 5. 83) ml] and 6MWD [ (328.46 ± 31.62) m vs. (396.75 ± 31.89) m] ,and significant reductions in left ventricular end systolic dimension [ (54. 12 ± 8.64) mm vs. (51.31 ± 8.26) mm] ,left ventricular end diastolic dimension [(65.25 ± 8. 86) mm vs.(62.14 ± 8.57) mm] ,levels of plasma BNP [ (572.59 ± 89. 62) mg／ml vs .(351.78 ± 81. 41) mg／ml] ,serum TNF‐α [ (24. 68 ± 5.83) ng／L vs. (21.05 ± 5. 39) ng／L] ,IL‐6 [(21.36 ± 4. 51) ng／L vs.(18.29 ± 4.34) ng／L] and hsCRP [(4. 89 ± 2. 15) ng／L vs. (3. 06 ± 1.47) ng／L] in levosimendan group , P＜0. 05 or ＜0. 01. There was no significant difference in incidence rate of adverse reactions during treatment between two groups , P＝0.690. Conclusion :Compared with dobutamine , levosimendan possesses more significant therapeutic effect on AHF .It can more significantly improve cardiac func‐tion ,exercise capacity and reduce cytokine levels in these patients .

Study on the characteristics of nerve damage by ultrasound combined with nerve conduction velocity in diabetic peripheral neuropathy / 中国医师进修杂志

Objective To analyze the characteristics of nerve damage in diabetic peripheral neuropathy by ultrasound and neuroelectrophysiological techniques and provide a basis for early diagnosis and treatment of diabetic peripheral neuropathy. Methods From January 2016 to May 2018, 225 patients with type 2 diabetes admitted to the hospital were divided into DPN group (110 cases) and non-diabetic peripheral neuropathy (NDPN) group (115 cases),and 120 healthy volunteers were as controls. Ultrasound and nerve conduction velocity(NCV) were used to analyze the characteristics of nerve damage in diabetic peripheral neuropathy(DPN). Results Among the three study groups, the sensory nerves conduction velocity and motor nerves conduction velocity of the ulnar nerve, median nerve, and common peroneal nerve were significantly reduced in the DPN group. But in the same group,the ulnar nerve, median nerve, and common peroneal nerve cross-sectional area (CSA) was significantly increased [(8.68 ± 1.89) mm2 vs. (6.79 ± 1.69) and (5.82 ± 1.57) mm2, (10.59 ± 1.82) mm2 vs. (7.98 ± 1.97) and (7.25 ± 1.71) mm2, (21.24 ± 2.53 )mm2 vs. (16.54 ± 2.49) and (15.40 ± 2.20) mm2]. In the measurement of sensory nerve conduction velocity, the abnormalities of ulnar nerve, median nerve and common peroneal nerve were significantly higher than thoseof motor nerve [34.54%(38/110) vs. 18.18%(20/110), 36.36% (40/110)vs. 20.90% (23/110), 52.72% (58/110) vs. 20.00% (22/110)]. In ultrasound and SCV, the proportion of ulnar nerve and median nerve injury was higher in patients aged 45 years or older or patients over 10 years of course (P<0.05). The proportion of median nerve injury was higher in patients with larger MAGE (P < 0.05). In the abnormal performance of ultrasound: the proportion of abnormal ulnar nerve, median nerve and common peroneal nerve in patients with large MAGE was significantly higher than that in patients with small MAGE (P<0.05); the results of ultrasound measurement of CSA showed that the ulnar nerve, median nerve and common peroneal nerve thickening were more obvious in patients with MAGE>4 mmol/L. Conclusions DPN affects sensory nerves first, and the proportion of injury is significantly higher than that of motor nerves; lower limb nerves are more susceptible to damage, compared with upper limb nerves; patients aged 45 years or older or patients with course over 10 years have a higher proportion of ulnar nerve and median nerve damage; patients with larger MAGE (>4 mmol/L) have a higher proportion of median nerve damage. The characteristics above can provide an effective basis for the prevention, diagnosis and treatment of DPN.

Metabolism, pharmacokinetics, and hepatic disposition of xanthones and saponins on Zhimu treatments for exploratively interpreting the discrepancy between the herbal safety and timosaponin A3-induced hepatotoxicity.

Timosaponin A3, a saponin in Zhimu, elicited hepatotoxicity via oxidative stress. However, the clinical medication of Zhimu has been historically regarded as safe, probably associated with the antioxidants it contains. However, the related information on the in vivo levels of timosaponin A3 and antioxidants remained unclear on Zhimu treatments. Therefore, a combination of the in vitro metabolism, including microbiota-mediated and liver-mediated metabolism, and in vivo pharmacokinetics and hepatic disposition, was conducted for three xanthones (neomangiferin, mangiferin, and norathyriol) and three saponins (timosaponin B2, timosaponin B3, and timosaponin A3) on Zhimu treatments. Consequently, following oral administration of Zhimu decoction to rats, those saponins and xanthones were all observed in the plasma with severe liver first-pass effect, where mangiferin was of the maximum exposure. Despite the ignorable content in the herb, timosaponin A3 elicited sizable hepatic exposure as the microbiota-mediated metabolite of saponins in Zhimu. The similar phenomenon also occurred to norathyriol, the microbiota-mediated metabolite of xanthones. However, the major prototypes in Zhimu were of limited hepatic exposure. We deduced the hepatic collection of norathyriol, maximum circulating levels of mangiferin, and timosaponin B2 and mangiferin interaction may directly or indirectly contribute to the whole anti-oxidation of Zhimu, and then resisted the timosaponin A3-induced hepatotoxicity. Thus, our study exploratively interpreted the discrepancy between herbal safety and timosaponin A3-induced hepatotoxicity. However, given the considerable levels and slow eliminated rate of timosaponin A3 in the liver, more attention should be paid to the safety on the continuous clinical medication of Zhimu in the future.

A conductive sodium alginate and carboxymethyl chitosan hydrogel doped with polypyrrole for peripheral nerve regeneration.

Polymer materials with electrically conductive properties have good applications in their respective fields because of their special properties. However, they usually exhibited poor mechanical properties and biocompatibility. In this work, we present a simple approach to prepare conductive sodium alginate (SA) and carboxymethyl chitosan (CMCS) polymer hydrogels (SA/CMCS/PPy) that can provide sufficient help for peripheral nerve regeneration. SA/CMCS hydrogel was cross-linked by calcium ions provided by the sustained release system consisting of d-glucono-δ-lactone (GDL) and superfine calcium carbonate (CaCO3), and the conductivity of the hydrogel was provided by doped with polypyrrole (PPy). Gelation time, swelling ratio, porosity and Young's modulus of the conductive SA/CMCS/PPy hydrogel were adjusted by polypyrrole content, and the conductivity of it was within 2.41 × 10-5 to 8.03 × 10-3 S cm-1. The advantages of conductive hydrogels in cell growth were verified by controlling electrical stimulation of cell experiments, and the hydrogels were also used as a filling material for the nerve conduit in animal experiments. The SA/CMCS/PPy conductive hydrogel showed good biocompatibility and repair features as a bioactive biomaterial, we expect this conductive hydrogel will have a good potential in the neural tissue engineering.

Pharmacokinetics of levornidazole disodium phosphate in monkey / 药学学报

This study was carried out to investigate the pharmacokinetics/bioequivalence of levornidazole disodium phosphate by using stable isotope labeled drug, evaluated the pharmacokinetic profile and confirmed the prodrug characteristics of levornidazole disodium phosphate in monkey. Levornidazole (Drug A) and stable isotope 15N labeled levornidazole disodium phosphate (Drug B) were mixed with equal mole amount (experiment I); stable isotope 15N labeled levornidazole disodium phosphate (Drug B) and levornidazole disodium phosphate (Drug C) were mixed with equal mole amount, respectively. After giving the mixed drugs to the monkey, the concentration of 15N-levornidazole disodium phosphate, levornidazole disodium phosphate, 15N-levornidazole and levornidazole in plasma samples of pre-dosing and 24 h after administration were analyzed by a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Pharmacokinetic calculations were performed through non-compartmental analysis using WinNonlin software. Two-sided 90% confidence intervals (CI) were used to evaluate the bioequivalence of two drugs. The results showed that levornidazole disodium phosphate was metabolized to levornidazole rapidly after administration, the body exposure were increased with the dosage. The method of bioequivalence used in this study was different from the traditional two periods, crossover design. By using the method of this study, the effects of administration period, intra-individual variability, and sequence of administration on bioequivalence were avoided. The results of this study had successfully supported the pharmacokinetic and bioequivalence study of this drug in human using the same approach.