Genotype-phenotype characteristics and baseline natural history of Chinese myelin protein zero gene related neuropathy patients.

BACKGROUND AND PURPOSE: The aim was to characterize the phenotypic and genotypic features of myelin protein zero (MPZ) related neuropathy and provide baseline data for longitudinal natural history studies or drug clinical trials. METHOD: Clinical, neurophysiological and genetic data of 37 neuropathy patients with MPZ mutations were retrospectively collected. RESULTS: Nineteen different MPZ mutations in 23 unrelated neuropathy families were detected, and the frequency of MPZ mutations was 5.84% in total. Mutations c.103_104InsTGGTTTACACCG, c.513dupG, c.521_557del and c.696_699delCAGT had not been reported previously. Hot spot mutation p.Thr124Met was detected in four unrelated families, and seven patients carried de novo mutations. The onset age indicated a bimodal distribution: prominent clustering in the first and fourth decades. The infantile-onset group included 12 families, the childhood-onset group consisted of two families and the adult-onset group included nine families. The Charcot-Marie-Tooth Disease Neuropathy Score ranged from 3 to 25 with a mean value of 15.85 ± 5.88. Mutations that changed the cysteine residue (p.Arg98Cys, p.Cys127Trp, p.Ser140Cys and p.Cys127Arg) in the extracellular region were more likely to cause severe early-onset Charcot-Marie-Tooth disease type 1B (CMT1B) or Dejerine-Sottas syndrome. Nonsense-mediated mRNA decay mutations p.Asp35delInsVVYTD, p.Leu174Argfs*66 and p.Leu172Alafs*63 were related to severe infantile-onset CMT1B or Dejerine-Sottas syndrome; however, mutation p.Val232Valfs*19 was associated with a relatively milder childhood-onset CMT1 phenotype. CONCLUSION: Four novel MPZ mutations are reported that expand the genetic spectrum. De novo mutations accounted for 30.4% and were most related to a severe infantile-onset phenotype. Genetic and clinical data from this cohort will provide the baseline data necessary for clinical trials and natural history studies.

One Case Report of Cavernous Angioma in Posterior Sagittal Sinus.

BACKGROUND: The Cavernous Angioma in Posterior Sagittal Sinus is exceedingly rare. METHODS: We report for the case of a 10-year-old male patient who was diagnosed with Cavernous Angioma in Posterior Sagittal Sinus. RESULTS: Our case is the second reported case of Cavernous Angioma in Posterior Sagittal Sinus in the world. CONCLUSIONS: It is very rare for the cavernous hemangioma to occur in the sinus, preoperative conventional MR scan lacks specificity and easily leads to misdiagnosis. Head MR enhancement, MRBTI, and SWI can provide more useful diagnostic information. The final diagnosis depends on the pathology examination.

Clinical and genetic features of Charcot-Marie-Tooth disease patients with IGHMBP2 mutations.

Autosomal recessive Charcot-Marie-Tooth disease Type 2S (AR-CMT2S) caused by IGHMBP2 mutation was first reported in 2014, and an increasing number of cases have been reported in the past eight years. We detected 15 distinct IGHMBP2 mutations among 8 typical AR-CMT2S families in our cohort of 178 Chinese CMT2 families using Sanger sequencing and next-generation sequencing (NGS), making IGHMBP2 mutations the most frequent cause of AR-CMT2 in our cohort. From 2014 to 2022, 34 AR-CMT2S families, including 45 patients and 47 different mutations, were reported. One third of identified mutations represented presumed loss-of-function variants (nonsense, frameshift and splicing), while two-thirds were missense changes which clustered in the helicase and ATPase domains. The age at onset ranged from 0.11 years to 20 years (mean±SD: 3.76±3.93 years) and the infantile (0-2 years) onset group accounted for the most patients (51.1%). The initial symptoms included muscle weakness (15, 33.3%), delayed milestones (9, 20%), feet deformity (8, 17.8%), gait disturbance (8, 17.8%), feet drop (7, 15.6%), frequent falls (3, 6.7%), hypotonia (2, 4.4%) and thenar atrophy (1, 2.2%). Molecular structural model analysis of 26 missense IGHMBP2 mutations using PyMOL software revealed that six mutations were close to the RNA-binding channel, eight mutations were in or close to the nucleotide-binding pocket. Based on available limited clinical information, it seems possible that missense changes located in or close to these motifs might be linked to a more severe clinical outcome. In conclusion, IGHMBP2 mutation screening should recommended for early-onset, moderately or severely affected, and sporadic or AR-CMT2 patients. A tiny minority of patients were relatively late onset and mild affected, which should be given more attention in genetic diagnosis and treatment. While our preliminary analysis suggests a potential link between the localization of missense mutations and clinical presentation, definition of genotype-phenotype relationships will require harmonized clinical information from a larger series of patients.

Relationship of Gingival Phenotypes and Faciolingual Thickness, Papilla Height, and Gingival Angle in a Chinese Population.

The objective of this study was to determine the normal values of faciolingual thickness (FLT) of the papilla base, papilla height (PH), and gingival angle (GA) among Chinese adults and the association of FLT with the gingival phenotype. The periodontal phenotypes of 105 volunteers were confirmed by Kan et al's periodontal probe transmission method and classification. All volunteers received complete supragingival scaling and were recalled after 1 week for clinical examination and for recording various periodontal indices, including Plaque Index, Gingival Index, and periodontal depth. The FLT, PH, and GA of maxillary anterior teeth were measured, and their associations were analyzed. The mean FLT of papilla between the right canine (CA) and lateral incisor (LI) was 8.11 ± 0.64 mm; between the right LI and central incisor (CI) was 7.77 ± 0.64 mm; between the right CI and left CI was 8.49 ± 0.66 mm; between the left CI and LI was 7.62 ± 0.63 mm; and between the left LI and CA was 8.17 ± 0.63 mm. The thin-phenotype group showed a greater PH and FLT than the thick phenotype group. Inversely, the GA of the thick-phenotype group was greater than the corresponding values for the thin-phenotype group. In Chinese residents, the high and thick papilla are associated with the thin phenotype, while the low and thin papilla are associated with the thick phenotype. The GA is negatively correlated with PH. A weak correlation exists between the GA and FLT of papilla.

Analysis of Crown Morphology and Gingival Shape in the Maxillary Anterior Dentition.

From a sample of 108 periodontally healthy volunteers with different combinations of morphometric data related to maxillary central anterior teeth and the surrounding soft tissues, this article aims to categorize gingival phenotypes according to tooth and gingival parameters, as well as assess the relationships between tooth shape and gingival characteristics, such as the papillary height (PH) and faciolingual thickness (FLT) of the papilla base. The periodontal phenotypes of 108 volunteers were confirmed using the periodontal probe transmission method for Kan classification. The FLT, PH, and the crown width to crown length (CW/CL) ratio for maxillary anterior teeth were measured. K-clustering was used to classify the anterior tooth shape into three groups: triangular, square, and compound. The mean CW/CL ratio for the maxillary anterior tooth position of the thick phenotype was greater than that of the thin phenotype. The PH and FLT for the maxillary anterior interdental papillae were greater for the thin phenotype group than for the thick phenotype group. A negative correlation was observed between the CW/CL ratio and both PH and FLT (P < .05 for both). However, a significant positive correlation was observed between FLT and PH. CW/CL ratio, FLT, and PH were all associated with the gingival phenotype with significant statistical correlations (P < .05 for all). Triangular teeth were correlated with scallop-shaped gingiva in the faciolingual area, while square teeth were associated with a flat gingiva.

CT guided percutaneous transhepatic microwave ablation for primary liver cancer in segment 9 / 中华肝胆外科杂志

Objective:To study the efficacy and safety of CT guided percutaneous transhepatic microwave ablation (PTPMWA) for primary liver cancer (PLC) in liver segment 9.Methods:A retrospective study was conducted on PLC patients between October 2013 and March 2019 at Dongguan People’s Hospital, Southern Medical University. Of 41 patients who entered into the study, there were 36 males and 5 females, with an average age of 59.1 years. These patients were diagnosed to have PLC in segment 9. The surgical related data and follow-up results were collected and analyzed.Results:All patients enrolled in the study completed the treatment procedure. CT scan was performed immediately after ablation which showed that the tumor areas to be completely covered by ablation. The duration of operation ranged from 45 to 260 (mean 91) min. The amount of bleeding during treatment was 1.0 to 5.0 (mean 1.4) ml. The complete response rate was 97.6% (40 patients) and the partial response rate was 2.4% (1 patient). The cumulative survival rates at 1, 2, 3, 4 and 5 years were 95.1%, 85.4%, 75.3%, 45.2% and 45.2%, respectively. Only 4 patients (9.8%) developed recurrence after treatment. The timings of recurrence were 1, 6, 13 and 67 months after treatment, respectively. The recurrent lesions were ablated again and complete response was obtained in all patients. There were no serious problems related to complications from ablation. The rate of postoperative complication was 7.3% (3 patients).Conclusion:PTPMWA is a novel treatment for patients with PLC in liver segment 9, the advantages of this treatment include good safety, high efficacy, low complications and local recurrence. The treatment is worthy of further future studies.

Genetic and clinical features of sorbitol dehydrogenase gene-related Charcot-Marie-Tooth disease in Chinese population / 中华神经科杂志

Objective:To report the genetic and clinical features of sorbitol dehydrogenase (SORD) gene-related Charcot-Marie-Tooth disease (CMT) in Chinese population.Methods:Fifty-seven undiagnosed sporadic or autosomal recessive (AR) inherited CMT2 families were collected from the Department of Neurology of the Third Xiangya Hospital from 2009 through 2018 .Polymerase chain reaction combined with Sanger sequencing were used to detect the mutations of SORD gene, and the relative clinical features were summarized. Results:The homozygous SORD gene hot spot mutation c.757delG (p. Ala253GlnfsTer27) was detected in four sporadic patients, accounting for about 7% of the total. Two patients with CMT2 phenotype were characterized by progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in both motor and sensory nerves. Two patients with distal hereditary motor neuropathy (dHMN) phenotype exhibited progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in motor nerves only. The age of onset was between five and 16 years, and the CMT neuropathy score was 2-9.Conclusions:The homozygous hot spot mutation of SORD gene (c.757delG, p.Ala253GlnfsTer27), and related childhood or adolescence onset, mildly affected CMT2/dHMN phenotypes are firstly reported in Chinese population. SORD gene-related CMT might be the most common subtype of AR-CMT2.

Erratum: Author correction to 'Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer' Acta Pharmaceutica Sinica B 2019; 9(5):1061-1077

[This corrects the article DOI: 10.1016/j.apsb.2019.03.006.].

Analysis on the characteristics of suspected vaccine-related deaths in Fujian Province, 2012-2017 / 中华预防医学杂志

Objective@#To analyze the characterisitics of the death cases suspected to be related to vaccination in Fujian Province from 2012 to 2017.@*Methods@#A total of 33 death cases information which was suspected to be related to the vaccinations from 2012 to 2017 were extracted from Chinese Adverse Events Following Immunization Information System (AEFI). The autopsy reports and the conclusions made by AEFI investigation diagnosis expert committee were collected at the same time. The inoculation data were obtained through the Fujian province Immunization Program Information System. The AEFI incidence, rare vaccine reaction incidences and mortality rates following immunization were figured out to analyze the characterisitics of the death cases associated with vaccination.@*Results@#The age of deuths cases was from 26 days to 52 months. Among 33 cases, 23 were males, and 8 were due to vaccine-related reaction, and the others were due to coincidental events. The number of rare vaccine reaction cases from 2012 to 2017 were 2,3,6,8,7 and 7, respectively. The highest AEFI incidence was measles and rubella combined attenuated live vaccine [38.88 (95%CI: 36.85-40.91)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [2.01 (95%CI: 1.73-2.30)/100 000 dose]. The highest rare vaccine reaction incidence was measles and rubella combined attenuated live vaccine [15.04 (95%CI: 13.78-16.30)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [0.38 (95%CI: 0.25-0.50)/100 000]. The highest mortality rate was inactivated poliomyelitis vaccine [0.26 (95%CI: 0.04-0.54)/100 000 doses], and the lowest mortality rate was measles, mumps and rubella combined attenuated live vaccine [0.01 (95%CI: 0.00-0.08)/100 000 doses]. The Spearman correlation analysis showed that there were correlations between AEFI incidence and rare vaccine reaction incidence (r=0.64, P=0.048), there were no correlations between AEFI incidence and mortality rate (r=-0.34, P=0.329), and there were no correlations between rare vaccine reaction incidence and mortality rate (r=-0.25, P=0.484).@*Conclusion@#Neither AEFI incidence nor rare vaccine reaction incidence was correlation with mortality rate. The main causes of death following vaccination were coincidental events.

Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer

Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin (RAP) into 7pep-modified PEG-DSPE polymer micelles (7pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor (TfR). Cytotoxic paclitaxel (PTX)-loaded micelle (7pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake and more tumor accumulation of micelles , 7pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7pep-M-PTX. Mechanism study further revealed that 7pep-M-RAP and 7pep-M-PTX used in combination provided enhanced efficacy through induction of both apoptosis- and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality.

Study on pharyngeal wall floppiness of patients with obstructive sleep apnea-hypopnea syndrome attributable to non-structural factors / 中华耳鼻咽喉头颈外科杂志

Objective@#Acoustic pharyngealmetry technology is utilized to evaluate the change and clinical significance of obstructive sleep apnea-hypopnea syndrome (OSAHS) patients caused by non-upper airway structural factor and normal individuals′ PWF(pharyngeal wall floppiness).@*Methods@#Acoustic pharyngealmetry instrument of Ecconvision was utilized to examine 102 OSAHS patients and 50 normal individuals, separately recorded their volume of pharyngeal cavity in sit or supine position, calculated PWF in sit or supine position, and SPSS 12.0 of tware was used to analyze data.@*Results@#PWF was 0.14±0.09 in sit position and PWF was 0.21±0.10, (t=5.96, t=9.63, P<0.001)in supine position of OSAHS group, which were all significantly higher than those of control group. PWFs in supine position of OSAHS group and control group were evidently higher than PWF(t=-11.91, P<0.001; t=-2.32, P=0.025) in sit position. ΔPWF(PWF_supine-PWF_sit)was 0.063±0.054 in OSAHS group which was significantly greater than in control(F=41.173, P<0.01). PWF in sit position and supine position were all positively related with age(r=0.714, r=0.735, P<0.001)while irrelevant with BMI(P>0.05).@*Conclusions@#PWF can be utilized to be an index to reflect the physiological feature of upper airway. PWF can more precisely reflect upper airway collapsibility of OSAHS patients on the condition of PWF in supine position. Pharyngeal wall floppiness quantified as a high PWF index is a non-structure vital factor of OSAHS patients and plays a role of guiding us to make personal treatment plans for OSAHS patients.

Effects of Baicalin on iNOS, NF-κB and Caspase-3 in Liver Ischemia Reperfusion Injury Rats / 中国中医药信息杂志

Objective To observe the effects of baicalin on forms of hepatic tissue, liver apoptosis, mRNA expressions of iNOS, NF-κB and protein expression of Caspase-3 in rats with ischemia reperfusion injury; To discuss its mechanism of action.Methods The rat models of liver ischemia reperfusion were performed according to the Pringle's method. Rats were randomly divided into sham-operation group, model group and baicalin group. Sham-operation group and model group were given normal saline for gavage, while baicalin group was given baicalin for gavage. Morphological characteristic was observed by HE staining. Hepatocyte apoptosis was determined by TUNEL. The mRNA expressions of iNOS and NF-κB were determined by RT-PCR. The protein expression of Caspase-3 was determined by Western blot.Results Compared with the sham-operation group, mRNA expressions of iNOS and NF-κB and the protein expression of Caspase-3 in the model group increased, as well as liver apoptosis rate (P<0.05,P<0.01); compared with the model group, mRNA expressions of iNOS and NF-κB and the protein expression of Caspase-3 in the baicalin group decreased, as well as liver apoptosis rate (P<0.05), and the hepatic lesion significantly improved in the baicalin group.Conclusion Baicalin can restrain Caspase-3 induced apoptosis by reducing the expressions of iNOS and NF-κB, with a purpose to realize the hepatoprotective effect for liver of rats with ischemia reperfusion injury.

Changes and significance of Th17 and Treg cells as well as their associated cytokines in peripheral blood of patients with chronic hepatitis C and cirrhosis / 中国免疫学杂志

Objective:To study the changes and significance of Th17 and Treg cells as well as their associated cytokines in pe-ripheral blood of patients with chronic hepatitis C and cirrhosis in order to investigate their role in the pathogenesis of chronic hepatitis C and hepatitis C cirrhosis. Methods:Flow cytometry and ELSIA assay were used to detect the expression ratio of Th17 and Treg cells and the serum levels of IL-10,TGF-β,IL-6 and IL-17 in peripheral blood of healthy human and patients with chronic hepatitis C and hepatitis C cirrhosis. Than we analyzed the differences of the above detection index between the healthy and patients with chronic hepatitis C and hepatitis C cirrhosis. Results:The expression ratio of Th17 cells (1. 33%±0. 30%) in peripheral blood of patients with chronic hepatitis C and IL-6[(8. 10±2. 42)ng/L] and IL-17[(16. 70±4. 73)ng/L] serum levels were significantly higher than those in the healthy (Th17:1. 14%±0. 19%) and IL-6[(1. 72±6. 70)ng/L],IL-17[(12. 29±1. 88)ng/L],P<0. 05;The expression ratio of Treg cells in peripheral blood of patients with hepatitis C cirrhosis and chronic hepatitis C patients was significantly higher than that in the healthy (6. 21%±0. 76%,5. 89%±0. 85% vs 5. 51%±0. 59% ),P<0. 05,The ratio of Th17/Treg in patients with cirrhosis was significantly lower than that in patients with chronic hepatitis C and the healthy(0. 19±0. 02 vs 0. 22±0. 03,0. 21±0. 03),P<0. 05;the levels of IL-1[(16. 21±3. 76)ng/L] and TGF-β[(5. 15±0. 83)ng/L] in peripheral blood of patients with hepatitis C cirrhosis were significantly higher than those in chronic hepatitis C[(14. 36±2. 78)ng/L;(4. 47±0. 87)ng/L] and the healthy[(14. 01±3. 01)ng/L;(4. 43±0. 98)ng/L)],P<0. 05. Conclusion:Th17 and Treg cells and their related cytokines involved in the process of chronicity of hepatitis C and cirrhosis,Th17 and Treg cells and their related cytokines in the treatment and prevention of chronicity of hepatitis C and cirrhosis may have important significance.

Surgical therapy for hepatocellular carcinoma with right diaphragmatic invasion / 中华肝胆外科杂志

Objective To review the indications,surgical methods,and matters which need attention in partial right diaphragmatic resection,and to summarize our experience of surgical therapy for hepatocellular carcinoma with right diaphragmatic invasion.Methods The clinical data of 27 patients with hepatocellular carcinoma which had invaded the diaphragm and had received partial right diaphragmatic resection and partial hepatectomy in our hospital from September 2008 to September 2012 were retrospectively analyzed.Results The operations were all performed successfully.The tumor diameter ranged from 5.0 to 15.0 cm (average 8.5 cm).The area of right diaphragm which was resected ranged from 9.0 to 50.0 cm2 (average 28.5 cm2).The operation time was 110～250 min (average 165 min),and blood loss was 450～2600 ml (average 870 ml).Diaphragmatic invasion was confirmed by postoperative histopathology in 9 patients (33.3％).A small quantity of right thoracic effusion was detected in all the cases postoperatively.Other complications included hepatic insufficiency in 4 patients and early postoperative bleeding,upper gastrointestinal bleeding,biliary fistula,and infection under the diaphragm in 1 case each.All patients recovered after conservative treatment.There was no perioperative death.19 patients received other postoperative adjuvant treatment while 6 patients refused further treatment and 2 patients were lost to follow-up.The 0.5-,1-,2,and 3 year survival rates after operation were 92.6％,81.5％,51.9％ and 33.3％ respectively.Conclusions Right diaphragmatic invasion is not a contraindication to surgery.Right diaphragmatic resection was safe and feasible,and postoperative long-term survival was satisfactory.

Prediction of the pharmacokinetic drug-drug interaction of pravastatin and pitavastatin with cyclosporine by a digital liver model based on metabolism and transporter / 药学学报

Information of metabolic enzymes and transporters, physiological parameters of animals and demography of Chinese people were integrated to establish a digital liver model (DLM) based on metabolism and transporter and coded with VBA. Clearance and drug-drug interaction (DDI) of candidate drugs in animal and human could be predicted based on the pharmacokinetic data obtained from in vitro and in vivo experiments. Pravastatin and pitavastatin were selected as the samples to examine this model, where their clearance and their DDI with cyclosporine were predicted. The results showed that the predicted values of median parameters in same species were within twofold of observed values for 83.3% (5/6). The program's successful prediction in DDI tendency might indicate its application in optimizing the dosage regimen and reducing the risk of clinical trial.

The MYB transcription factor superfamily of Arabidopsis: expression analysis and phylogenetic comparison with the rice MYB family.

MYB proteins are a superfamily of transcription factors that play regulatory roles in developmental processes and defense responses in plants. We identified 198 genes in the MYB superfamily from an analysis of the complete Arabidopsis genome sequence, among them, 126 are R2R3-MYB, 5 are R1R2R3-MYB, 64 are MYB-related, and 3 atypical MYB genes. Here we report the expression profiles of 163 genes in the Arabidopsis MYB superfamily whose full-length open reading frames have been isolated. This analysis indicated that the expression for most of the Arabidopsis MYB genes were responsive to one or multiple types of hormone and stress treatments. A phylogenetic comparison of the members of this superfamily in Arabidopsis and rice suggested that the Arabidopsis MYB superfamily underwent a rapid expansion after its divergence from monocots but before its divergence from other dicots. It is likely that the MYB-related family was more ancient than the R2R3-MYB gene family, or had evolved more rapidly. Therefore, the MYB gene superfamily represents an excellent system for investigating the evolution of large and complex gene families in higher plants. Our comprehensive analysis of this largest transcription factor superfamily of Arabidopsis and rice may help elucidate the possible biological roles of the MYB genes in various aspects of flowering plants.

Management of main hepatic vein injury in hepatectomy for hepatic neoplasm of segment Ⅷ / 中华肝胆外科杂志

Objective To summarize the experience in management of main hepatic vein injury due to hepatectomy for hepatic neoplasm of segment Ⅷ. Methods Clinical data of 64 patients suffering from main hepatic vein injury due to hepatectomy of hepatic neoplasm of segment Ⅷ in our hospital from October 1996 to October 2008 were retrospectively analyzed. Results Both the main trunks of the middle and right hepatic vein were injured in 34 patients, single right hepatic vein in 13 and middle hepatic vein in 17. In these patients with hepatic vein injury, the main trunk of the hepatic vein was repaired in 39, vessels ligated in 12 and direct liver wound surfaces sutured in 12. The hepatectomy and hemostasis were successfully performed during operation in all patients. After operation, 3 patients had active bleeding and 2 patients were reoperated on to sew up the bleeding points by wadding with the gelatin sponge and discharged after rehabilitation. One patient gave up treatment and was discharged automatically. Conclusion Main hepatic vein injury in hepatectomy of hepatic neoplasm of segment Ⅷ can be managed effectively by hepatic vein repair, hepatic vein ligation and suture of the liver section that can be chosen to control the bleeding of hepatic vein injury according to the actual conditions.

Assessment of Biliary Excretion of Ceftriaxone Sodium in Humans / 医学研究杂志

Objective To study biliary excretion of ceftriaxone sodium in humans. Methods Twelve biliary calculi patients were infused with a single dose of 2.0g ceftriaxone half an hour before operation and the common bile duct bile and gallbladder bile samples were coUected in the operations. The bile drug concentrations were assayed by HPLC. Results The results of clinical study on the bile drug showed that the concentrations (C) of ceftriaxone in common bile duct and gallbladder were (264.43±166.46) μg/ml and (85.39 ±48.16) μg/ml, respectively. Conclusion Ceftriaxone reaches high concentrations in humans' bile, and it could be chosen as a good antibiotics for the treament of biliary infection.

Selectively expressing SARS-CoV-2 Spike protein S1 subunit in cardiomyocytes induces cardiac hypertrophy in mice.

Cardiac injury is common in hospitalized COVID-19 patients and portends poorer prognosis and higher mortality. To better understand how SARS-CoV-2 (CoV-2) damages the heart, it is critical to elucidate the biology of CoV-2 encoded proteins, each of which may play multiple pathological roles. For example, CoV-2 Spike glycoprotein (CoV-2-S) not only engages ACE2 to mediate virus infection, but also directly impairs endothelial function and can trigger innate immune responses in cultured murine macrophages. Here we tested the hypothesis that CoV-2-S damages the heart by activating cardiomyocyte (CM) innate immune responses. HCoV-NL63 is another human coronavirus with a Spike protein (NL63-S) that also engages ACE2 for virus entry but is known to only cause moderate respiratory symptoms. We found that CoV-2-S and not NL63-S interacted with Toll-like receptor 4 (TLR4), a crucial pattern recognition receptor that responsible for detecting pathogen and initiating innate immune responses. Our data show that the S1 subunit of CoV-2-S (CoV-2-S1) interacts with the extracellular leucine rich repeats-containing domain of TLR4 and activates NF-kB. To investigate the possible pathological role of CoV-2-S1 in the heart, we generated a construct that expresses membrane-localized CoV-2-S1 (S1-TM). AAV9-mediated, selective expression of the S1-TM in CMs caused heart dysfunction, induced hypertrophic remodeling, and elicited cardiac inflammation. Since CoV-2-S does not interact with murine ACE2, our study presents a novel ACE2-independent pathological role of CoV-2-S, and suggests that the circulating CoV-2-S1 is a TLR4-recognizable alarmin that may harm the CMs by triggering their innate immune responses.