[Incidence and risk factors of thromboembolism in patients with lung cancer receiving immunotherapy].

Objective: To evaluate the incidence of thromboembolism in a cohort of patients with lung cancer who received immune checkpoint inhibitors (ICIs), and explore relevant clinical risk factors. Methods: We retrospectively collected and analyzed the clinical data of patients with confirmed primary lung cancer and treated with ICIs between March 2018 and June 2021 at three hospitals in China (Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Fudan University Shanghai Cancer Center and Zhongshan Hospital of Fudan University). The cumulative incidence and risk factors of thromboembolism in these patients were analyzed using a competitive risk model. Results: A total of 804 patients were enrolled, there were 623 males and 181 females, with a median age of 59 years (ranged 28-86 years). Of these, 62 patients encountered 65 thromboembolic events, including 51 venous thromboembolism events (VTE) and 14 arterial thromboembolism events. The cumulative incidence of thromboembolism events at 3, 6, 12 and 24 months were 4.3%, 6.1%, 10.1% and 16.8%, respectively. And the cumulative incidence of venous thromboembolism events at 3, 6, 12 and 24 months were 3.4%, 4.7%, 9.0% and 13.3%, respectively. Multivariate analysis showed that history of thromboembolism (HR=6.345, 95%CI: 2.917-13.802,P<0.001),liver metastasis (HR=2.249, 95%CI: 1.123-4.502,P=0.022) and peripherally inserted central venous catheter (HR=3.674, 95%CI: 1.751-7.712, P<0.001) were independent risk factors for venous thromboembolism during ICIs therapy in patients with lung cancer. Conclusions: Patients with lung cancer under ICIs therapy are at high risk of thromboembolism. And history of thromboembolism, liver metastasis and peripherally inserted central venous catheter are risk factors of venous thromboembolism.

Genomic origin and EGFR-TKI treatments of pulmonary adenosquamous carcinoma.

BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

Effect of NT-3 on infection-induced memory impairment of neonatal rats.

OBJECTIVE: To explore the effect of neurotrophin-3 (NT-3) messenger ribonucleic acid (mRNA) in the hippocampus on infection-induced memory impairment of neonatal rats. MATERIALS AND METHODS: 80 female Sprague-Dawley (SD) rats in the neonatal stage were selected to establish memory impairment model by bacterial meningitis infection. Rats were randomly divided into experimental group (n=40) and control group (n=40). Rats in experimental group were injected with ß-amyloid precursor protein 319-335 peptide APP17p into brain tissue to up-regulate the expression of NT-3, and the rats in control group didn't receive treatment. Behavioral changes of rats were observed in Morris water maze and passive avoidance experiment. Apoptosis of nerve cells was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method and Fluoro-Jade B method. NT-3 mRNA expression level was measured via reverse transcription polymerase chain reaction (RT-PCR). RESULTS: NT-3 expression level in experimental group was higher than that in control group (p<0.05). Apoptosis rate of nerve cells in experimental group was lower than that in control group, but the learning and memory ability of rats in experimental group was better than that in control group (p<0.05). CONCLUSIONS: Reduced NT-3 expression level may be correlated with the occurrence of meningitis because NT-3 can suppress nerve cell apoptosis and ameliorate learning and memory impairment to a certain extent to exert neuroprotective effects.

A study on correlations of procalcitonin and interleukin-6 with viral meningitis.

OBJECTIVE: To study the change rules of inflammatory factors in cerebrospinal fluid (CSF) and serum of patients with viral meningitis. PATIENTS AND METHODS: 742 patients with suspected viral meningitis admitted to Department of Neurosurgery in our hospital from August 2012 to May 2016 were selected as research objects and retrospectively analyzed. 536 patients were diagnosed with viral meningitis by CSF with the lumbar puncture and brain computed tomography (CT), while the other 206 patients were diagnosed with non-infectious nervous system disease, as the control group. The levels of inflammatory factors interleukin-6 (IL-6) in peripheral blood and procalcitonin (PCT) in cerebrospinal fluid were detected and compared between two groups of patients. RESULTS: Compared with those in control group, the white blood cell (WBC) count, and levels of serum IL-6 and PCT in cerebrospinal fluid of patients with viral meningitis were all increased (p<0.01). PCT and IL-6 were positively correlated with viral meningitis (r=0.8267, 0.9234). The sensitivity of the two items was 77.81% and 81.32%, respectively, and the specificity was 90.53% and 88.64%, respectively. CONCLUSIONS: The levels of inflammatory factors IL-6 and PCT in serum and CSF of patients with viral meningitis are slightly increased. The detection of the expression levels of IL-6 and PCT in patients with viral meningitis is of great significance for the preliminary diagnosis and rehabilitation of viral meningitis.

[Treatment of glottic cancer involving the anterior commissure by transoral CO(2) laser surgery].

Objective: To study the clinical outcome of transoral CO(2) laser surgery for glottic cancer involving the anterior commissure. Methods: Thirty-two cases of glottic cancer involving the anterior commissure treated by transoral CO(2) laser surgery between March 2009 and December 2013 were retrospectively reviewed. Among these cases, 27 were T1bM0M0, 5 were T2N0M0. All cases were followed-up for more than 3 years. Results: All the 32 cases were successfully treated. Perioperative complications included injuries in the soft palate mucosa(13/32, 40.63%), loose incisors(3/32, 9.38%) and subcutaneous emphysema in the neck(2/32, 6.25%). During the follow-up period, granulation was found in all cases. Three cases had local recurrence. Two patients treated by a secondary transoral CO(2) laser surgery and the other case had total laryngectomy, all three cases were followed up for 5 years without recurrence. Two cases had regional recurrence but no primary site recurrence. One patient was treated by neck dissection, and followed up for 5 years without recurrence. The other patient died of supraclavicular and mediastinal lymph node metastasis and lung metastasis 40 months after operation. The overall 5-year survival rate was 90.6%. There was no significant difference in survival rate between T1bN0M0(92.6%) and T2N0M0(80.0%) (Log Rank χ(2)=0.788, P=0.375). The overall 5-year local regional control rate was 84.4%. In T1bN0M0 lesions, the 5-year local regional control rate was 92.6%, which was significantly higher than that in T2N0M0 lesions(40.0%) (Log Rank χ(2)=9.504, P=0.002). Conclusion: With appropriate surgical indication, detailed preoperative evaluation, good surgical skill, transoral CO(2) laser surgery may achieve satisfactory outcome in the treatment of glottic cancer involving the anterior commissure.

Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease.

The article "Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease" by Q.-B. Lu, Z.-F. Zhu, H.-P. Zhang, W.-F. Luo, published in Eur Rev Med Pharmacol Sci 2017; 21 (7): 1514-1521 has been withdrawn.

Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease.

OBJECTIVE: In the gastrointestinal neural system, the emergence of Lewy Body (LB) is usually earlier than the clinical diagnosis of Parkinson (PD) motor symptoms. Therefore, this study is aimed to explore whether the LB in the gastrointestinal tract of prodromal PD patients. PATIENTS AND METHODS: 98 paraffin embedded tissue specimens from 57 PD patients were collected in the Second Affiliated Hospital of Soochow University archives, as well as 98 tissue specimens of 90 non-PD patients undergone surgical resection. The pathological sections were stained by the immune-histochemistry method. The positive staining of aggregated a-Synuclein (a-a-syn) and phosphorylated a-Synuclein (p-a-syn) in gastrointestinal tract were counted to analyze the distribution of the expression of a/p-a-syn in the prodromal PD patients before diagnosis (0-5 years, 6-10 years, 11-20 years). RESULTS: According to results from the immunohistochemical staining of a/p-α-syn, 35 (52.23%) and 30 (44.78%) tissue blocks were positively stained respectively in total 67 tissue blocks provided from 39 prodromal PD patients. And there were 46 (46.94%) and 25 (25.51%) positive staining in 98 tissue blocks from the control group. In 31 tissue blocks collected from 18 PD patients, there were 19 (61.29%) and 15 (48.39%) tissue blocks with the a/p-a-syn positive staining. Compared with non-PD patients from the control group, the a-a-syn positive rate was not significantly increased in the pre- and post-diagnosis PD patients (p>0.05). However, p-a-syn of both groups increased significantly (p<0.05). Also, the positive expression rate of a/p-a-syn in the 6-10-year group was lower than that in the 0-5-year and 11-20-year, and the positive rate of the 0-5-year group was the highest (p<0.05). CONCLUSIONS: p-a-syn as the main component of Lewy body of nervous system in the gastrointestinal track may be used as a characteristic predictive marker of PD and the prevention of PD disease.

[Prospective study of riskfactors of difficult laryngeal exposure in suspension laryngoscopy].

Objective:The aim of this study was to demonstrate the risk factors which affect the exposure of glottis in suspension laryngoscopy.Method:We performed a prospective study about 90 cases of vocal cord lesions underwent microlaryngosurgery(including polyps,vocal nodules,cyst and papilloma).Then we recorded the clinical data related to glottic exposure, both preoperatively and intraoperatively. Result:Univariate analysis showed that parameters like age(P=0.038), Cormack-Lehane score(P=0.007),maximuminterincisors gap(P=0.007),hyoid-mental distance(HMD) in full extension(P=0.033), thyroid-mental distance(TMD) in full extension(P=0.014), vertical thyroid-mental distance(VTMD) in full extension(P=0.042), sternum-mental distance(SMD) in full extension(P=0.01) and degree of neck flexion-extension(P=0.003) were related to intraoperative difficult exposure of the glottic area.In logistic regression analysis, Cormack-Lehane score(P=0.003), maximuminterincisors gap(P=0.001) and degree of neck flexion-extension(P=0.002) were significantly risk factors of difficult laryngealexposure. Conclusion:Combination of Cormack-Lehane score, maximuminterincisors gap and degree of neck flexion-extensionmay help to predict the difficult laryngealexposure, so we should evaluate patients before operations of suspension laryngoscopy to decrease the surgical complication.

[Study on the pharyngeal constriction and function of cricopharyngeal muscle in normal persons using dynamic magnetic resonance imaging].

OBJECTIVE: To investigate the superiority of dynamic magnetic resonance imaging as an assessment method of pharyngeal constriction and cricopharyngeal muscle function, and introduce a new way to measure the pharyngeal constriction ratio, anteroposterior diameter of esophageal entrance and thickness of cricopharyngeal muscle in healthy volunteers. METHODS: Twenty volunteers who were assessed as normal by fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study were included in this study. With the use of 3.0T magnetic resonance imaging, Fiesta sequence and Asset technique, the median sagittal plane and intervertebral transverse plane from C1 to C5 were scanned repeatedly. Pharyngeal constriction ratio in the median sagittal and intervertebral transverse plane, anteroposterior diameter of esophageal entrance and thickness of cricopharyngeal muscle were assessed and the data were analysed by SPSS13.0. RESULTS: The intervertebral transverse plane between C1 and C2 was superior in observation of pharyngeal constriction ratio in the same way that the plane between C4 and C5 was superior in cricopharyngeal evaluation. The average of sagittal and intervertebral pharyngeal constriction ratio were estimated as 0.08±0.02, 0.09±0.04 respectively and the average of thickness of cricopharyngeal muscle and anteroposterior diameter of esophageal entrance were (6.50±1.69) mm, (1.99±0.76) mm respectively. CONCLUSION: Dynamic magnetic resonance imaging was superior in assessing the function of pharyngeal constriction and cricopharyngeal muscle by scanning the swallowing process in the median sagittal and intervertebral transverse plane.

[Microenvironment of middle meatus involved in pathogenesis of nasal polyps-the possibility and research progress].

Chronic rhinosinusitis with nasal polyps(CRSwNP) is a complicated inflammatory disease, with increasing incidence and high recurrence rate,which the pathogenesis remains unclear. This article reviewed research progress about the relationships between middle meatus microenvironments and pathologic process of CRSwNP: including hypoxia ,microbiome imbalance, innate function of the airway epithelial barrier dysfunction. Pointing out a new direction to figure out pathogenesis of CRSwNP.

Association between the LXRα polymorphism and stroke in a Chinese population.

We examined the relationship between the liver X receptor α gene (LXRα) polymorphism and the susceptibility to stroke. We utilized the single fluorescent-labeled probe technique to detect the genotype of rs12221497 in the LXRα gene in 400 stroke patients and 400 healthy control subjects. The difference in genotype distribution between the 2 groups was analyzed using the chi-square test. Serum lipids and glucose levels between the different genotypes were also compared. We found that the risk of stroke in carriers with the AA + GA genotype was 2.02-fold higher than that in GG genotype carriers (odds ratio = 2.02, 95% confidence interval = 1.18-2.87, P < 0.05), and that the risk of stroke in carriers with the A allele increased by 0.606-fold compared to that in G allele carriers (odds ratio = 1.606, 95% confidence interval = 1.158-2.228). Logistic regression analysis showed that after adjusting for other confounding factors, the A allele was an independent risk for stroke. However, there were no differences in serum lipids and glucose levels between each genotype. We conclude that the rs12221497 polymorphism in the LXRα gene was associated with the susceptibility to stroke in a Han Chinese population.

The diagnostic value of high-resolution ultrasonography for the detection of anterior disc displacement of the temporomandibular joint: a meta-analysis employing the HSROC statistical model.

The study aimed to assess the diagnostic value of high-resolution ultrasonography (HR-US) in the detection of anterior disc displacement (ADD) of the temporomandibular joint. Relevant trials reported in MEDLINE, the Chinese National Knowledge Infrastructure Database, the Chinese Biomedical Literature Database, and Embase were identified. A manual search was also performed. The quality of retrieved data was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. Data were extracted and cross-checked, and a statistically rigorous meta-analysis was performed using a hierarchical summary receiver operating characteristic model (HSROC). The clinical utility of results was assessed using Fagan nomograms (Bayes theory). All data were evaluated using Stata software. A total 11 studies including 1096 subjects were included in the analysis; all reported the utility of HR-US for the diagnosis of ADD with reduction (ADDWR) and without reduction (ADDWoR). For ADDWR, the weighted sensitivity and specificity were 0.83 (95% confidence interval (CI) 0.78-0.88) and 0.85 (95% CI 0.76-0.92) respectively. The lambda value was 3.41 (95% CI 2.37-4.46) and the Fagan nomogram pre-test probability 58%, with a positive likelihood ratio (LR) of 6.01. The positive post-test probability was 89%, with a negative LR of 0.20. The negative post-test probability was 21%. The positive increase in diagnostic utility was 31% and the negative decrement in that value 37%. For ADDWoR, the weighted sensitivity and specificity values were 0.72 (95% CI 0.59-0.81) and 0.90 (95% CI 0.86-0.93), respectively. The lambda value was 3.69 (95% CI 2.39-4.99) and the Fagan nomogram pre-test probability 38%, with a positive LR of 7.00. The positive post-test probability was 82%, with a negative LR of 0.32. The negative post-test probability was 16%. The increase in diagnostic utility was 44% and the negative decrement in that value 22%. HR-US delivers acceptable performance when used to diagnose ADD, being superior for the detection of ADDWoR than ADDWR, and exhibiting a lower negative diagnostic value in the detection of ADDWoR than ADDWR. HR-US may serve as a new method for the rapid diagnosis of ADD. The method has the advantages of simplicity and low cost. Given the uncertainty in some of the estimated values, more high-quality studies are needed to assess that diagnostic efficacy.

Assessment of cerebral iron content in patients with Parkinson's disease by the susceptibility-weighted MRI.

OBJECTIVE: The overall goal of this study was to evaluate the usability of the susceptibility weighted imaging (SWI) in (1) assessment of iron deposition to enhance our ability to detect PD in the early phase and (2) in estimation of the degree of PD. PATIENTS AND METHODS: SWI scans were carried out in 54 patients with PD (18 patients with the Hoehn-Yahr scale < 1.5 and 36 patients with the Hoehn-Yahr stage > 1.5) and 40 control individuals. The phase values of the substantia nigra, red nucleus, caudate nucleus, putamen, and globus pallidus were measured on the corrected phase image. RESULTS: Compared with control individuals, patients with both the early and intermediate/ advanced stages of PD had significantly different phase values in the substantia nigra, red nucleus, caudate nucleus, putamen, and globus pallidus (all p < 0.05). The phase values of the substantia nigra and globus pallidus inversely correlated with the Hoehn-Yahr scale (respectively, r = -0.845, p < 0.05, and r = -0.868, p < 0.05). Weaker correlations were found between the phase values of red nucleus, caudate nucleus, putamen, and Hoehn-Yahr scale (red nucleus r = -0.543, caudate nucleus r = -0.620, p < 0.05, putamen r = -0.537). CONCLUSIONS: A semi-quantitative assessment of the iron content of the substantia nigra and globus pallidus with the help of SWI may be useful for early diagnosis of PD and evaluation of the degree of this disease.

Cervical oesophagostomy in patients with severe dysphagia following radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to investigate the validity and feasibility of cervical oesophagostomy as a treatment for patients with severe dysphagia after radiotherapy for nasopharyngeal carcinoma. METHODS: The study retrospectively analysed the clinical data, symptoms, physical signs, treatment and outcomes of 12 patients treated with cervical oesophagostomy for severe dysphagia after radiotherapy for nasopharyngeal carcinoma, from 2006 to 2010. RESULTS: In all 12 cases, the oesophageal stoma remained stable, without any complications such as pharyngeal fistula or inflammation. No oesophageal stricture or granuloma growth was observed. All patients reported significant improvement in their nutritional status and quality of life after the oesophagostomy surgery. CONCLUSION: Cervical oesophagostomy is a valid and feasible method of treating severe dysphagia following radiotherapy for nasopharyngeal carcinoma. Oesophagostomy shows specific advantages over nasogastric tubing, gastrostomy and jejunostomy. Patients' nutrition and quality of life can be improved significantly if cervical oesophagostomy is executed in a timely fashion, especially in cases with severe trismus and multiple radiation-induced cranial nerve palsies unresponsive to rehabilitation.

Parathyroid hormone regulates osterix and Runx2 mRNA expression predominantly through protein kinase A signaling in osteoblast-like cells.

Runt-related transcription factor 2 (Runx2) and osterix are osteoblast-specific transcription factors essential for the development of osteoblastic cells and bone formation. PTH given intermittently has anabolic effects on bone; however, the exact role remains to be understood completely. The purpose of this study was both to investigate whether PTH regulates Runx2 as well as osterix expression and to identify the signaling used. Using RT-PCR, we confirmed that PTH (1-34) regulated Runx2 and osterix mRNA expression, in rat osteoblast-like cell line UMR 106, in a dose- and time-dependent manner. PTH in low concentrations stimulated both Runx2 and osterix mRNA expression while that in high concentrations did not. Forskolin, an adenylate cyclase activator, also enhanced Runx2 and osterix transcription, and the stimulatory effects of PTH and forskolin were blocked by the pre-treatment of the cells with H-89, a protein kinase A (PKA) inhibitor. In contrast, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) had no effect on Runx2 transcription, but induced an increase in osterix mRNA level at the concentration of 500 nM at 12 h after treatment. Moreover, pre-treatment of the cells with calphostin C, a PKC-specific inhibitor, reduced the increase in osterix transcripts enhanced by PTH and PMA 12 h after treatment. However, these inhibitory effects were not sustained for longer terms. These observations demonstrate that PTH stimulates Runx2 and osterix expression in vitro, at least in part, at transcriptional level. Induction of Runx2 mRNA is mediated through the activation of cAMP/PKA signal transduction. In the case of osterix, although the increase in mRNA level is predominantly mediated via cAMP/PKA signaling, PKC activation might also be involved in this process.

[The comparison of genetic divergences and its relationships to heterosis revealed by SSR and RFLP markers in rice (Oryza sativa L.)].

Genetic divergences of 57 entries from 6 ecotypes of rice were surveyed by PCR analysis with 48 pairs of SSR and by Southern analysis by 50 RFLP probes. It was indicated that SSR markers detected polymorphism efficiently in comparison to RFLP markers, considering the allele numbers per locus and average gene diversity. Among all of 1,596 pairs, 1,452 pairs of genetic distances based on SSR data (GDSSR) were higher than the genetic distance based on RFLP data (GDRFLP) by average of 0.2492. The average GDSSR of entries within indica subspecies was 0.5483, but GDRFLP was only 0.2776. And the GDSSR and GDRFLP of entries with japonica subspecies were 0.577, 0.2405 respectively. The average GDSSR between varieties of interspecies was 0.8074, and the average GDRFLP was 0.7310. It is suggested that the GDSSR between varieties of introspecies or interspecies are higher than that of GDRFLP. The analysis of correlation between GDSSR and GDRFLP of any entry with other 56 entries indicated that the correlation coefficient for typical Indica or Japonica varieties were higher, but lower for Indica-like or Japonica-like materials. It was also found that the relationships between genetic distance based on these two kinds of markers and the yield of hybrid performance were not significant, but most of the correlation coefficient between heterosis and GDRFLP or GDSSR arrived at highly significant level.

[Evaluation of clinical therapeutic efficacy by injecting adriamycin to the nerve in primary trigeminal neuralgia].

Sixty-eight cases suffering from primary trigeminal neuralgia were performed by injecting adriamycin to the nerve. The results show that the symptoms of trigeminal neuralgia completely disappeared in all the cases during two weeks after the operation in which 63.2% in 24 hours, 28.9% in one week and 7.9% in two weeks. the recurrence rate in three years was 10.3% and in three to five years was 15.4%. This technique has the features of low recurrence rate, steady therapeutic effect, safety and microtrauma.

Mhc-DRB genes of the pigtail macaque (Macaca nemestrina): implications for the evolution of human DRB genes.

The DRB family of human class II major histocompatibility complex (Mhc) loci is unusual in that individuals differ in the number and combination of genes (haplotypes) they carry. Indications are that both the allelic and haplotype polymorphisms of the DRB loci predate speciation. Searching for the evolutionary origins of these polymorphisms, we have sequenced five DRB clones isolated from a cDNA library of a pigtail macaque (Macaca nemestrina) B lymphocyte line. The clones represent five different genes which we designate Mane-DRB*01-Mane-DRB*05. The genes appears to be approximately equidistant from each other, so that allelic relationships between them cannot be established on the basis of the sequence data alone. If positions coding for the peptide-binding region of the class II beta chains are eliminated from sequence comparisons, the Mane-DRB genes appear to be most closely related to the human (HLA) DRB1 genes of the DRw52 group. We interpret this finding to indicate that the ancestral gene of the DRw52 group of human DRB1 alleles separated from the rest of the HLA-DRB1 alleles before the separation of the Old World monkeys (Cercopithecoidea) from the apes (Hominoidea) in the early Oligocene. After this separation, the ancestral DRB1 gene of the DRw52 group duplicated in the Old World monkey lineage to give rise to genes at three loci at least, while in the ape lineage this gene may have remained single and diverged into a number of alleles instead. These findings suggest that some of the polymorphism currently present at the DRB1 locus is greater than 35 Myr old.

[Influence of carbenicillin on pharmacokinetics of ribostamycin in 7 volunteers when they were used combinedly].

The experiment consists of two groups, namely the ribostamycin (Rib) group and the Rib and carbenicillin (Car) combination group. There were 7 healthy volunteers in each group. The Rib concentration in blood and urine was detected with the improved microbiology method. The organism tested was Bacillus pumilus. The results demonstrated that the drug serum level was in line with the one-compartment open model. The parameters such as K, Ka, T1/2, T1/2a, Tp, Cmax, and AUC in the Rib group and the combination group were 0.43 +/- 0.03 and 0.41 +/- 0.04 h-1, 3.09 +/- 1.37 and 2.82 +/- 1.48 h-1, 1.61 +/- 0.12 and 1.72 +/- 0.17 h, 0.26 +/- 0.12 and 0.31 +/- 0.15 h, 0.91 +/- 0.20 and 1.01 +/- 0.31 h, 37 +/- 4 and 34 +/- 6 micrograms.ml-1, 123 +/- 17 and 120 +/- 16 micrograms.h.ml-1, respectively. The 24-h urinary recovery rates of the 2 groups were 84 +/- 3% and 84 +/- 5%, respectively. There was no significant difference (P greater than 0.05) between the parameters of the 2 groups. The results indicate that Car has no apparent effect on the pharmacokinetics of Rib in the healthy volunteers.