AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Diagnosis and outcome analysis of diseases characterized by recurrent low-frequency sensorineural deafness / 临床耳鼻咽喉头颈外科杂志

The aim of this study was to explore the clinical features, hearing prognosis and differential diagnosis of recurrent low frequency sensorineural hearing loss （RLFD） . The clinical characteristics, clinical manifestations, audiological examination and auxiliary examination of RLFD patients were retrospectively analyzed. We summarized clinical features, draw the pure tone audiometry curves, and analyze the diagnosis of RLFD. Forty-seven patients （53 ears） with RLFD had a hearing review time of 1-124 months. The course of disease ranged from 3 to 320 months with an average course of 29 months. ①The incidence of tinnitus in the accompanying symptoms was 93.6%（44 cases）, and the ear suffocation was 83.0%（39 cases）, 38.3% （18 cases） of the patients developed vestibular symptoms during the course of the disease. ②During the observation period, 27 cases（57.4%） were diagnosed with related diseases: 7 cases（14.9%） Meniere's disease, 6 cases（12.8%） vestibular migraine, 2 cases（4.3%） with Meniere's disease and migraine, and 1 case（2.1%） with idiopathic intracranial hypotension 11 cases（23.4%） were possible cochlear migraine; ③Migraine-related RLFD had a younger onset age, more common in women; ④83.0%（44 ears）of the affected ears had stable or improved low-frequency hearing during the observation period, 17.0%（9 ears）of the affected ears experienced low-frequency hearing; ⑤18.9%（10 ears）of the affected ears had high-frequency hearing loss; ⑥RLFD had 6 types of audiological outcomes: low-frequency improvement combined with high-frequency stability; low-frequency stability combined with high-frequency stability; low frequency progress combined with high frequency stability type; low frequency improvement combined with high frequency progress type; low frequency stability combined with high frequency progress type; low frequency progress combined with high frequency progress type; ⑦Rising type hearing curve low frequency hearing prognosis is good, mountain type and descending low frequency hearing prognosis is poor. Tinnitus and ear stuffiness are the early symptoms and the most disturbing symptoms in patients with RLFD. The mechanism of Migraine may play an important role in the pathogenesis of RLFD. The rare causes such as intracranial hypotension syndrome should not be ignored. Most of the patients with RLFD had stable or improved hearing after long-term fluctuation, but some patients with low or high frequency hearing might decline. The type of initial hearing curve was a prognostic factor. Long-term hearing follow-up is helpful for prognosis evaluation.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

Effects of Suhuang Zhike Capsule on inflammation of airways in patients with allergic rhinitis and asthma syndrome / 中国综合临床

Objective:To investigate the effect of Suhuang Zhike Capsule on airway inflammation in patients with acute episode of allergic rhinitis and asthma syndrome.Methods:Eighty patients with allergic rhinitis and asthma syndrome were admitted to North China University of Science and Technology Affiliated Hospital from June 2016 to September 2017.A prospective cohort study was carried out and randomly divided into treatment group and control group with 40 patients in each group.The control group was treated with conventional anti-inflammatory, expectorant and antiasthmatic therapy, while the treatment group was treated with Suhuang Zhike Capsule.The changes of nasal symptoms and asthma clinical symptoms in the two groups were compared before and after treatment, and the changes of nitric oxide in exhaled air, eosinophils in blood and induced sputum were measured.Results:Compared with the control group, there was no significant difference in the number of eosinophils in the exhaled nitric oxide, eosinophil count in blood and induced sputum before treatment in the treatment group ((161.45±4.67)×10 -9 vs.(163.12±4.56)×10 -9, (1.59±0.53)×10 9/L vs.(1.60±0.51)×10 9/L, (1.11±0.06)×10 9/L vs.(1.18±0.09)×10 9/L; t values were 0.10, 0.44, 1.75, respectively, all P>0.05). After treatment, the exhaled nitric oxide, eosinophil count in blood and induced sputum in the treatment group were significantly lower than those before treatment((30.86±5.54)×10 -9 vs. (161.45±4.67)×10 -9; (0.32±0.05)×10 9/L vs. (1.59±0.53)×10 9/L; (0.06±0.02)×10 9/L vs. (1.11±0.06)×10 9/L, t values were 91.32, 41.63, 51.77, respectively, all P<0.01). In the treatment group, the effective rate of nasal symptom control was 85.0% (34/40) significantly higher than 62.5% (25/40) in the control group (χ 2=5.23, P<0.05), and the effective rate of asthma clinical symptom control was significantly higher than that in the control group(90.0%(36/40), 72.5%(29/40), χ 2=4.02, P<0.05). Conclusion:Suhuang Zhike capsule can obviously improve the airway inflammatory response of patients with allergic rhinitis asthma syndrome in the acute attack stage, and the combination of conventional treatment plan is helpful to improve the curative effect.

Diagnosis and outcome analysis of diseases characterized by recurrent low-frequency sensorineural deafness / 临床耳鼻咽喉头颈外科杂志

Objective@#The aim of this study was to explore the clinical features, hearing prognosis and differential diagnosis of recurrent low frequency sensorineural hearing loss （RLFD） . @*Method@#The clinical characteristics, clinical manifestations, audiological examination and auxiliary examination of RLFD patients were retrospectively analyzed. We summarized clinical features, draw the pure tone audiometry curves, and analyze the diagnosis of RLFD. @*Result@#Forty-seven patients （53 ears） with RLFD had a hearing review time of 1-124 months. The course of disease ranged from 3 to 320 months with an average course of 29 months. ①The incidence of tinnitus in the accompanying symptoms was 93.6%（44 cases）, and the ear suffocation was 83.0%（39 cases）, 38.3% （18 cases） of the patients developed vestibular symptoms during the course of the disease. ②During the observation period, 27 cases（57.4%） were diagnosed with related diseases: 7 cases（14.9%） Meniere's disease, 6 cases（12.8%） vestibular migraine, 2 cases（4.3%） with Meniere's disease and migraine, and 1 case（2.1%） with idiopathic intracranial hypotension 11 cases（23.4%） were possible cochlear migraine; ③Migraine-related RLFD had a younger onset age, more common in women; ④83.0%（44 ears）of the affected ears had stable or improved low-frequency hearing during the observation period, 17.0%（9 ears）of the affected ears experienced low-frequency hearing; ⑤18.9%（10 ears）of the affected ears had high-frequency hearing loss; ⑥RLFD had 6 types of audiological outcomes: low-frequency improvement combined with high-frequency stability; low-frequency stability combined with high-frequency stability; low frequency progress combined with high frequency stability type; low frequency improvement combined with high frequency progress type; low frequency stability combined with high frequency progress type; low frequency progress combined with high frequency progress type; ⑦Rising type hearing curve low frequency hearing prognosis is good, mountain type and descending low frequency hearing prognosis is poor. @*Conclusion@#Tinnitus and ear stuffiness are the early symptoms and the most disturbing symptoms in patients with RLFD. The mechanism of Migraine may play an important role in the pathogenesis of RLFD. The rare causes such as intracranial hypotension syndrome should not be ignored. Most of the patients with RLFD had stable or improved hearing after long-term fluctuation, but some patients with low or high frequency hearing might decline. The type of initial hearing curve was a prognostic factor. Long-term hearing follow-up is helpful for prognosis evaluation.

Tannic acid enhances cisplatin effect against hepatocellular carcinoma HepG2 by endoplasmic reticulum stress pathway / 重庆医学

Objective To investigate the synergistic effects of tannic acid(TA) and cis-dichlorodiamine platinum(CDDP) on hepatocellular carcinoma HepG2 cells and its activation situation of endoplasmic reticulum stress(ERS) pathway.Methods Human hepatocellular carcinoma HepG2 cells were divided into the control group,TA group,CDDP group and TA+CDDP group,and were cultured in vitro for 24 h.The growth inhibitory effect of medication on HepG2 cells was detected by MTT assay.The pharmacodynamics synergistic effect between the two drugs was analyzed by the drug interaction index,drug dose reduction index and equivalent graphical method.The nucleus changes were observed by DAPI staining.Real time fluorescent quantitative PCR(q-RT-PCR) and Western blot were used to detect the levels of ERS markers glucose regulated protein (GRP)78 and GRP94.Results TA and CDDP had dose-dependent growth inhibition effect on HepG2 cells,their median effective concentrations(IC50) were 360.00 μmol/L and 1.80 μg/mL respectively.The combination treatment of 180.00 μmol/L TA and 0.90 μg/mL CDDP on HepG2 cells could enhance the inhibitory effect on cell growth.Ta and CDDP had synergistic effect for inhibiting hepatocellular carcinoma cells growth.Compared with the TA group and CDDP group,cell shrinkage and rounding were accelerated in the combined group,apoptotic cells were increased,nuclear had pyknosis,irregular edge and dense staining,nuclear fragmentations were increased and the expressions of GRP78 and GRP94 were up-regulated.Conclusion TA can enhance the effect of CDDP on anti-hepatic carcinoma HepG2 cells,and the synergy mechanism may be related to the activation of ERS pathway.

Imaging features of 55 cases of solitary pulmonary nodules / 中国基层医药

Objective To analyze the imaging features of solitary pulmonary nodules (SPN).Methods The clinical data and chest imaging features of 55 cases with SPN confirmed by pathology were retrospectively analyzed . Results Of the 55 patients,40 cases (80.00％) were lung cancer and 15 cases (20.00％) were benign lesions . The univariate analysis showed that the age of patients (t=2.972,P=0.004),lobulation sign (χ2 =7.018,P=0.008) and pleural indentation sign (χ2 =4.727,P=0.030) had statistically significant differences in distinguish of the benign and malignant nodules ,but the sex (χ2 =1.760,P=0.185),nodule site (χ2 =0.145,P=0.703),burrs (χ2 =0.555,P=0.456),cavity (χ2 =0.000,P=1.000),nodule size (t=0.608,P=0.546) and other factors had no significant difference.Multivariate Logistic regression analysis showed that age (OR=1.101,P=0.022) and lobulation sign (OR=6.187,P=0.026) were independent influencing factors for judgement of the benign and malig -nant SPN.Conclusion The age of patients,lobulation sign and the pleural indentation sign are related to the benign and malignant SPN .Age and lobulation sign are the independent influencing factors for judgement of the benign and malignant SPN .

Tannic acid enhances cisplatin-induced apoptosis of hepatocellular carcinoma HepG2 cells by activating ATF6-CHOP pathway / 实用医学杂志

Objective To detect the activation levels of endoplasmic reticulum stress ATF6-CHOP pathway,and to investigate the molecular mechanism of tannic acid (TA) combined with cisplatin (CDDP) against hepatocellular carcinoma.Methods HepG2 cells were cultured with 180 μM TA or/and 0.9 μg/ml CDDP for 24 h or 48 h.The levels of ATF6 (ATF6α),ATF6B (ATF6β) and CHOP were analyzed by real-time fluorescence quantitative PCR (q-RT-PCR) and western blot.Results We found that after 24 h or 48 h,compared with the control group,ATF6 mRNA and protein levels,ATF6B protein level,CHOP mRNA and protein levels were significantly increased in the TA group,CDDP group or combination group (P ＜ 0.01 or P ＜ 0.05).Conclusion TA can combine with CDDP to increase the levels of endoplasmic reticulum stress ATF6-CHOP pathway,and the ATF6-CHOP pathway may be one of the molecular mechanisms synergistic anti-hepatocellular carcinoma effect of TA and CDDP on HepG2 cells.

Evaluation of treatment for high intra-abdominal cryptorchidism of children with transumbilical single-site and multichannel laparoscopic single stage Fowler-Stephens orchiopexy / 中华实用儿科临床杂志

Objective To evaluate the clinical effect of treatment for high intra-abdominal cryptorchidism of children with transumbilical single-site and multichannel laparoscopic single stage Fowler-Stephens (F-S) orchiopexy.Methods The case records of the intra-abdominal cryptorchidism of children who had undergone transumbilical single-site laparoscopic single stage F-S orchiopexy were reviewed retrospectively in Children's Hospital Affiliated to Capital Institute of Pediatrics between January 2011 and January 2017,were assigned as the observation group,whose age ranged from 1 to 8 years and average age was 18 months,with 22 unilateral and 8 bilateral,38 testis in total.A total of 31 children with intra-abdominal cryptorchidism who had undergone laparoscopic two stage F-S orchiopexy were assigned as the control group,whose age was from 11 months to 9 years and average age was 20 months,with 23 unilateral and 8 bilateral,39 testis in total.Postoperative follow-ups were conducted with the evaluation index included the testical position,with or without atrophy.The procedure effect and postoperative complications were observed,and the difference between two operation methods was evaluated.Results Operations in all cases were successful in both groups without intraoperative complication.A total of 38 testis were operated with single stage F-S orchiopexy in the observation group,and 39 testis were operated with two stage F-S orchiopexy in the control group.Postoperative complications included scrotum wound infection one case and scrotum hematoma in one case in the observation group,and abdominal wall emphysema in one case,intestinal obstruction in one case as well as umbilicus infection 1 case in control group.Follow-ups ranged from 6 months to 6 years,median 24 months.All testicals were within the scrotum,and each group had 1 case of testical atrophy.The difference of postoperative complication and effect between two groups had no statistical significance(x2 =0.184,0.107,all P ＞ 0.05).Conclusions Outcomes between single stage and two stage F-S orchiopexy are similar.The transumbilical single-site laparoscopic F-S orchiopexy not only has the satisfactory effect,but also saves some patients from reoperation and secondary anaesthesia,but doctors must be aware of the indications and contraindications of this procedure should be brought to attention.

Choice of handling methods for internal ring during transumbilical single-site laparoscopic orchiopexy for cryptorchidism with bilateral processus vaginalis unclosed in children / 中华实用儿科临床杂志

Objective To explore the choice of handling methods for bilateral internal ring during the transumbilical single-site laparoscopic orchiopexy for cryptorchidism with bilateral processus vaginalis unclosed in children,and evaluate the clinical effect.Methods Retrospective analysis was conducted for the clinical data of 102 children with cryptorchidism and bilateral processus vaginalis unclosed who were hospitalized at Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2011 to January 2016.They were divided into the observation group (55 cases) and the control group(47 cases).In the observation group,the internal rings of the affected side were destroyed and stitched with a needle between the edge of arcuate of musculus trasversus abdominis and fascia trans versalis of posterior peritoneum.If the diameter of opposite internal ring was less than 0.5 cm,only a circle was destroyed.Otherwise,a circle was destroyed and sutured with a needle.In the control group,the processing methods for orchiopexy and affected side internal ring were same as the observation group.Purse string suture was done for opposite internal rings of all cases in the control group.The parameters of operative duration,intraoperative blood loss,postoperative hospital stay,postoperative complications were compared between 2 groups.Results All operations were successful in both groups,spermatic cords were reserved and testicles were in scrotum of all cases.Operative duration was significantly shorter in the observation group than that in the control group [(42.02 ± 3.21) min vs.(48.43 ± 4.18) min,t =-8.739,P ＜ 0.01].The differences in intraoperative blood loss,postoperative hospital stay and postoperative complications between 2 groups were not statistically significant[(4.38 ± 1.42) mL vs.(4.80 ± 1.37) mL,t =-1.533,P ＞0.05;(2.87 ±0.64) dvs.(2.98 ±0.61) d,t =-0.853,P ＞0.05;1.8％ (1/55 cases) vs.2.1％(1/47 cases),x2 =0.013,P ＞ 0.05].During a mean follow-up of 30(12-72) months,there was no case of testicular ascent or atrophy,or hernia,or hydrocele.Conclusions The transumbilical single-site 3-port laparoscopic orchiopexy for cryptorchidism has stable efficacy.The improved method for bilateral internal ring is simple and has satisfactory effect,which is worthy of clinical promotion.

Formation and evolution of hair follicle stem cell proliferative region and stem cell niche during the development of murine hair follicles / 中华皮肤科杂志

Objective To preliminarily analyze the formation and significance of stem cell niche in the hair follicle bulge,based on the morphological structure of murine vibrissa follicles and localization of proliferative region of hair follicle stem cells at different developmental stages.Methods Vibrissa follicles of healthy,specific pathogen-free (SPF) outbred KM mice at different developmental stages were labelled with 5-ethynyl-2-deoxyuridine (EdU) as a marker of proliferating stem cells by in vivo local injection.After 24 hours,the complete vibrissa follicles were obtained by surgical microanatomy,and then subjected to OCT embedding,cryostat sectioning and hematoxylin-eosin (HE) staining.Sections labelled with EdU were subjected to immunofluorescence staining to determine the active proliferative region of hair follicle cells.Hair follicles were subjected to immunofluorescence staining with anti-stem cell transcription factor (Sox2) antibody.Results The morphology of hair follicles changed during the development,and mature hair follicles could be clearly observed in the hair follicle bulge.On day 1 to day 15 after birth,the active proliferative region of murine hair follicle cells was gradually transferred from the dermal papillae to the inner and outer root sheaths in the hair follicle bulb.Meanwhile,along with the inner and outer root sheaths,the actively proliferating hair follicle cells migrated upward to the middle and upper parts of hair follicles and formed the hair follicle bulge,in which the stem cell transcription factor Sox2 was abundantly expressed in cells.Conclusions Progenitor cells in the stem cell niche of the hair follicle bulge are derived from the dermal papillae of hair follicles.After the formation of the hair follicle bulge,cells start to abundantly express Sox2 and enter into the resting state.

Clinical study of non-invasive positive pressure ventilation for the overlap syndrome complicated with pulmonary encephalopathy / 实用医学杂志

Objective To observe the value of non-invasive positive pressure ventilation for the overlap syndrome complicated with pulmonary encephalopathyt.Methods Fifty-six patients with the overlap syndrome complicated with pulmonary encephalopathy were divided into the experinental group and the controlled group.The experimental group was treated with non-invasive positive pressure ventilation and conventional clinical therapy (drugs and oxygen).The controlled group was treated with conventional clinical therapy.Results The experimental group was better than tche Controlled group in blood gas analysis (PH、PaCO2) in the second hour and the twentyfourth hour after treatment (P ＜ 0.05).The experimental group was more than the controlled group in the improvement of consciousness disorder (P ＜ 0.05).The experimental group was less than the controlled group in tracheal intubation (P ＜ 0.05).Conclusion Non-invasive positive pressure ventilation could improve consciousness disorder of the overlap syndrome complicated with pulmonary encephalopathy,and reduce tracheal intubation.

Net case-control study on relationship between base level of Cyfra21-1,SCCA,TK1 and lung cancer prognosis / 中国免疫学杂志

Objective:To investigate the relationship between base level of Cyfra21-1,SCCA,TK1 and lung cancer prognosis.Methods: A nested case-control study was conducted.721 lung cancer cases who had no distant metastasis were recruited baseline population from January 2010 to January 2013.About 2 years follow-up,364 cases of death or brain (or multiple) metastasis were identified as case group, and the other 357 cases were included in the control group.The level of serum Cyfra21-1,SCCA,TK1 was detected.The relationship between base level of Cyfra21-1,SCCA,TK1 and lung cancer prognosis were analyzed.Results: The age in the case group was (59.3±10.1),and the control group was (59.0±9.9).There were obvious differences in body mass index,smoking index,pathological type,clinical stage,lymph node metastasis and with chronic diseases between case group and control group(P0.05).There were differences in the base level of Cyfra21-1,SCCA,TK1;and there were differences in Cyfra21-1,SCCA,TK1 distribution between case group and control group(P0.05) in patients with different stages of lung cancer.There were differences in the base levels of Cyfra21-1 and SCCA(P0.05) in patients with different pathological types of lung cancer.Logistic regression analysis results showed that the OR value of SCCA,TK1 with lung cancer prognosis were respective 7.235(1.674-14.613),5.009(0.973-10.778),5.816(0.879-16.235).Conclusion: The baseline level of Cyfra21-1 can reflect the prognosis of lung cancer patients,while SCCA,TK1 not.

Effect of phentolamine on N terminal B-type natriuretic peptide precursor,blood gas analysis,hypersensitive c-reactive protein and plasma D-dimer in patients with chronic cor pulmonale / 中国综合临床

Objective To observe the influence of phentolamine on N terminal B-type natriuretic peptide precursor(NT-proBNP),blood gas analysis,hypersensitive c-reactive protein and plasma D-dimer in patients with chronic cor pulmonale Methods One hundred and one cases patients with chronic cor pulmonale were randomly divided into two groups,51 patients in the treatment group,50 patients in the control group.All patients were treated with normal anti-infection,eliminating phlegm to smooth wheezing antithrombotic for one week,as the same time patients in the treatment group were treated with phentolamine for one week.Through observed the treatment effect of phentolamine to chronic cor pulmonale,the level of NT-proBNP,blood gas analysis,hypersensitive c-reactive protein and plasma D-dimer in patients with chronic cor pulmonale before and after the treatment were analyzed.Results Compared with before treatment,the levels of NT-proBNP,PCO2,hypersensitive c-reactive protein,plasma D dimer were lower than after one week in two groups,while the level of PO2 was higher.Treatment group:NT-proBNP (1 712.76±572.32) ng/L vs.(271.59±163.05) ng/L,t=20.42,P<0.05,PCO2 (66.34±5.81) mmHg vs.(52.58±5.82) mmHg,t=16.46,P<0.05,PO2 (59.28±6.13) mmHg vs.(73.64±6.10) mmHg,t=23.02,P<0.05,hypersensitive c-reactive protein 86.0(28.0) mg/L vs.23.0(12.0) mg/L,Z=-6.22,P<0.05 mg/L,plasma D-dimer (4 953.37±1 654.09) μg/L vs.(1 847.90±838.66) μg/L,t=17.11,P<0.05.Control group:NT-proBNP (1 527.24±658.70) ng/L vs.(612.58±357.59) ng/L,t=14.52,P<0.05,PCO2 (65.41±5.23) mmHg vs.(56.46±5.65) mmHg,t=13.04,P<0.05,PO2(60.57±5.84) mmHg vs.(67.21±5.19) mmHg,t=-10.06,P<0.05,hypersensitive c-reactive protein 79.0(29.0) mg/L vs.43.0(20.0) mg/L,Z=-6.16,,P<0.05,plasma D-dimer (4 408.02±1 682.83) μg/L vs.(2 598.28±1 242.73) μg/L,t=12.15,P<0.05.But the levels of NT-proBNP,PCO2,hypersensitive c-reactive protein and plasma D-dimer reduced significantly,the level of PO2 increased more significantly in treatment group(t(z)=-6.19,-3.39,-7.16,-3.56,5.70,all P<0.05).Conclusion Phentolamine can reduce the level of NT-proBNP,PCO2,hypersensitive c-reactive protein and plasma D-dimer and increased the level of PO2 in patients with chronic cor pulmonale.Phentolamine combined with routine treatment can improve the clinical efficacy of patients with chronic cor pulmonale.

The effect of edaravone on cognition function and expression of Nogo-A in rats with serious intermittent hypoxia / 中国中西医结合急救杂志

Objective To observe the effect of edaravone (ED) on cognition function and expression of Nogo-A in prefrontal cortex neuron of rats with serious intermittent hypoxia.Methods Ninety-six adult male Wistar rats were randomly divided into normal control group, chronic intermittent hypoxia (CIH) model group and ED group, 32 rats in each group. The rat model of CIH was reproduced in a low oxygen box at 08:00-15:00 every day: alternatively, different flow rates of nitrogen and compressed air were given, 120 seconds being one cycle, maintaining the oxygen concentration at 5%-21% in the low oxygen chamber; the normalcontrol group was continuously under the circumstance fulfilled with compressed air. The rat in ED group was given intravenous injection of 3 mg/kg ED in a tail vein at 07:00 daily. After modeling for 7, 14, 21, 28 days, the learning and memory functions of rats were assessed with the Morris water maze test, and the reactive oxygen species (ROS) content in the rat prefrontal lobe tissue was detected; the level of Nogo-A protein expression in the rat prefrontal cortex was examined by immunohistochemical method .Results ① Rat learning results: in CIH model group, with the time prolongation escaping latency period was gradually longer, since 14 days after the modeling, the difference was statistically significant compared with that in normal control group, while the learning time in ED group was obviously shorter than that in the CIH model group (seconds: 14 days was 26.97±3.35 vs. 34.95±3.36, 21 days was 32.78±4.59 vs. 46.72±4.11, 28 days was 41.39±3.84 vs. 57.35±3.72, allP < 0.05). ② Rat memory results: the rats in CIH model group, with the time prolongation crossing the target quadrant time was gradually shorter, since 14 days after the modeling, the difference was statistically significant compared with that of the normal control group, while the memory time in the ED group was obviously longer than that of the model group (seconds: 14 days was 42.72±3.35 vs. 39.88±3.56, 21 days was 40.48±4.62 vs. 28.72±3.93, 28 days was 31.13±3.46 vs. 22.79±3.24, allP < 0.05). ③ ROS content: with the time prolongation, ROS content was gradually increased in CIH model group, but the ROS content in ED group was significantly lower than that in CIH model group at various time points (MU/L: 7 days was 13.27±0.23 vs. 17.68±0.51, 14 days was 15.51±0.28 vs. 20.41±0.65, 21 days was 20.29±0.44 vs. 23.86±0.35, 28 days was 24.46±0.53 vs. 30.43±0.85, allP < 0.05). ④ Protein expression of Nogo-A: with the time prolongation, the protein expression of Nogo-A was gradually increased in CIH model group, they reached the peak on the 14th day, the expression of Nogo-A [absorbance (A) value] in ED group were significantly lower than that in CIH model group at each time point (×103: 7 days was 4.80±0.70 vs. 5.99±0.62, 14 days was 5.89±0.90 vs. 7.42±0.66, 21 days was 4.92±0.64 vs. 5.90±0.37, 28 days was 3.59±0.59 vs. 4.27±0.40, allP < 0.05).Conclusions The mechanism of ED has a valid therapeutic effect on the cognitive dysfunction induced by serious intermittent hypoxia in rats, ED can remove oxygen free radicals and inhibit the protein expression of Nogo-A in the prefrontal cortex, so ED can alleviate the damage of cognitive function in rats with CIH.

Correlation between plasma NGAL and ET-1 levels and cognitive dysfunction in patients with chronic obstructive pulmonary disease / 中华行为医学与脑科学杂志

Objective To investigate the relationship between the plasma neutrophil gelatinase-associated lipocalin (NGAL)and endothelin-1 (ET-1) levels and cognitive dysfunction in chronic obstructive pulmonary disease (COPD) patients.Methods A case-control study was performed,consisting of 128 patients with COPD(68 patients without cognitive dysfunction and 60 patients with cognitive dysfunction) and 70 normal controls.All patients with COPD were diagnosed by pulmonary function tests and plasma levels of NGAL and ET-1 were determined by enzyme immunoassay.The cognitive function was evaluated by the MMSE and MoCA.Results ①Compared with normal control,the levels of plasma NGAL and ET-1 were increased(NGAL:(2.20±0.60) μg/L vs (1.69±0.73) μg/L,P＜0.05;ET-1:(26.19± 10.55)pg/ml vs (13.05±2.37) pg/ml,P＜0.05) in COPD patients without cognitive dysfunction and in COPD patients with cognitive dysfunction(NGAL:(3.80±2.75) μg/L vs (1.69±0.73) μg/L,P＜0.01;ET-1:(37.82±0.29) pg/ml vs (13.05±2.37) pg/ml,P＜0.01).Compared with the COPD patients without cognitive dysfunction,the levels of plasma NGAL and ET-1 were also increased in COPD patients with cognitive dysfunction (all P＜0.05).②The plasma NGAL levels were correlated negatively with MMSE scores(r=-0.524,P＜0.05),and negatively correlated with MoCA scores (r=-0.527,P＜0.05).The plasma ET-1 levels were negatively correlated with MMSE scores(r=-0.549,P＜0.05),and negatively correlated with MoCA scores(r=-0.558,P＜0.05).The levels of NGAL and ET-1 were positively correlated(r=0.564,P＜0.05).Conclusion NGAL and ET-1 may be involved in the pathophysiological process of cognitive dysfunction in patients with COPD,which provides a certain clinical value for the assessment of cognitive dysfunction in patients with COPD.

Impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese renal transplant recipients / 中国药理学通报

Aim To investigate the impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese stable renal transplant re-cipients. Methods Pharmacokinetics of once daily-ta-crolimus( tac-q. d. ) and twice daily-tacrolimus( tac-b. i. d. ) were determined by CLIA, CYP3A5 genotype was measured by PCR-RFLP. Each 10 patients receiv-ing tac-q. d. and tac-b. i. d. respectively were en-rolled, and each 5 patients receiving tac-q. d. were matched to poor metabolizer ( PM ) and extensive me-tabolizer ( EM ) group respectively according to CYP3A5 genotypes. Results AUC0~24 h for tac-q. d. was 1. 78 folds higher than AUC0~12 h for tac-b. i. d. , and dose-adjusted C0 was 40% lower for tac-q. d. than for tac-b. i. d. There were no significant differences for other parameters between the two groups; Cmax, AUC0~24 h and C0 were 1. 75, 1. 96 and 2. 49 folds higher for PM than for EM, and dose-adjusted Cmax, AUC0~24 h and C0 were 1. 80, 2. 34 and 2. 64 folds higher for PM than for EM. There were good correla-tions between AUC0~24 h and C0 for tac-q. d. Conclu-sion Conversion from tac-b. i. d. to tac-q. d. results in requirement of increased tacrolimus dose and detec-tion of CYP3A5 genotype, which is necessary for ensu-ring C0 in the range of therapeutic window.