Design, synthesis and biological activity of DB02 amino acid derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors / 药学学报

To improve the stability of amino acid ester derivatives of DB02, a series of 24 amide derivatives of DB02 amino acids as non-nucleoside HIV-1 reverse transcriptase inhibitor were designed and synthesized based on bioisosterism by replacing amino acid ester scaffold with more stable amide bond. The anti-HIV-1 activity of these compounds was evaluated by MTT assay and counting the number of syncytia. Most of the target compounds showed a potential anti-HIV-1 activity, among which compounds 2d, 2i, 2l, 2s, and 2w had better antiviral effect than lead compound DB02, with a therapeutic index > 1 000.00. Finally, the structure-activity relationship of these compounds was discussed, which provided new ideas for the further development of DB02 derivatives.

The scheme for validation of clinical metagenomics sequencing assay / 中华检验医学杂志

Clinical metagenomic next-generation sequencing (mNGS) entails unbiased shotgun sequencing of all microbial and host nucleic acids present in a clinical sample. By analyzing the microbiota diversity, taxonomic, and phylogenetic relationships of clinical specimens, metagenomics related analysis provides an opportunity to investigate substantial biological significance of different microbes. According to the published paper, most studies on mNGS mainly focused on the clinical impact evaluation. However, the studies focused on the analytical performance validation of mNGS before clinical application were rare. Here, a scheme, included intended use, method establishment, assay validation and standard operating protocol, for the laboratory validation of clinical metagenomics sequencing assay was provided by summarizing experiences of clinical laboratory department of Peking Union Medical College Hospital protocol and relevant research. In this scheme, we discussed important topics of mNGS laboratory validation as below: specimen type and pathogen list, bioinformatics pipeline setup, dry lab standard preparation and performance validation, mNGS workflow setup, background nucleotide acid evaluation, wet lab standard preparation and performance validation.

Application of a new plastic biliary stent modified based on pigtail nasal bile drainage tube to hilar biliary cholangiocarcinoma / 中华消化内镜杂志

Objective:To compare the efficacy and safety of a new type of plastic biliary stent modified based on the pigtail nasobiliary duct and the common plastic biliary stent for hilar cholangiocarcinoma.Methods:Data of a total of 38 patients with obstructive jaundice caused by hilar cholangiocarcinoma who received endoscopic retrograde cholangiopancreatography (ERCP) palliative treatment at the Endoscopy Center, General Hospital of Northern Theater Command from June 2018 to December 2020 were collected, including 20 cases using the new type of plastic biliary stent (the new stent group), and 18 cases using the common plastic stent (the common stent group). Patients were followed up to May 30, 2021. The procedure time, hospital stay, postoperative biliary infection incidence, the bilirubin decrease, and the patency time of the stents in the two groups were compared.Results:The procedure time was 19.85±1.07 minutes in the new stent group and 22.00±3.38 minutes in the common stent group, respectively, showing no significant difference between them ( t=1.26, P=0.607). The lengths of hospital stay of the two groups were 11.45±2.39 days and 11.33±3.51 days, respectively, showing no significant difference between them ( t=-0.52, P=0.938). The median margins of total bilirubin reduction in the two groups were 122.85 μmol/L and 96.25 μmol/L, respectively, with significant difference ( Z=-2.03, P=0.042). The incidence of long-term cholangitis of the new stent group was significantly lower than that of the common stent group [10.0% (2/20) VS 44.4% (8/18), P=0.027]. The patency time of the new stent group was significantly longer than that of the common stent group (109.45±32.67 days VS 82.11±20.95 days) with significant difference ( t=2.23, P=0.032). Conclusion:In the palliative treatment of hilar bile duct obstruction, the new plastic bile duct stent modified based on pigtail type can reduce the incidence of long-term cholangitis and prolong the patency of bile duct stent compared with the common stent group.

Risk signal mining of adverse event related to adalimumab based on FAERS / 中国药房

OBJECTIVE To provide reference for clinical safe and rational use of adalimumab by mining the risk signals of adverse event （AE）. METHODS AE reports related to adalimumab were collected from FDA adverse event reporting system （FAERS）from Jan. 1st，2015 to Dec. 31th，2021. The reporting odds ratio （ROR）method and the Medicines and Healthcare Products Regulatory Agency （MHRA） method were adopted to mine the AE risk signals related to adalimumab ，AEs were classified and described by using the preferred system organ class （SOC）and preferred term （PT）of Medical Dictionary for Regulatory Activities （23.0）. RESULTS A total of 149 203 AE reports related to adalimumab were screened ，among which 65 218 cases（43.71％）were severe AE reports. A total of 2 660 PTs were mined ，involving 27 SOCs. PTs related to primary disease （arthralgia，Crohn’s disease ，rheumatoid arthritis ，abdominal pain ，osteoarthritis，intestinal obstruction ，psoriasis，joint swelling ， arthritis，etc.）were more frequently reported ，followed by PTs related to inflammation and pain （procedural pain ，inflammation， etc.）. The main SOC included musculoskeletal and connective tissue diseases （68 227 cases），gastrointestinal diseases （50 682 cases），injury，poisoning and procedural complications （32 404 cases），infections and infestations （15 651 cases），general disorders and administration site conditions （15 424 cases），etc. CONCLUSIONS It is suggested to pay attention to the possible occurrence of paradoxical psoriasis and lupus-like syndrome related to the autoimmune system when using adalimumab clinically ； at the same time ，the attention should be paid to serious infection ，tuberculosis，malignant tumors ，demyelination，congestive heart failure and other AEs. If related AEs occurs ，intervention measures should be taken in time. Great importance should be paid to intracranial aneurysms ，ovarian cysts ，coronary artery occlusion ，thyroid masses and other AEs not mentioned in the instrcution ，to ensure the medication safety of patients.

ADE Risk Signal Mining Related to Belimumab Based on the FARES Database / 中国药房

OBJECTIVE：To prov ide referen ce for clinical safe and rational use of belimumab by mining the risk signals of adverse drug event （ADE）. METHODS ：ADE reports related to belimumab were collected from FDA adverse event reporting system（FAERS）from the first quarter of 2015 to the first quarter of 2021. The reporting odds ratio （ROR）method and the Medicines and Healthcare Products Regulatory Agency （MHRA）method were adopted to mine the ADE risk signals related to belimumab，setting the threshold as the number of reports ＞3 and the lower limit of 95％ CI ＞1（ROR method ）and the proportional reporting ratio （PRR）＞2，and χ2 ＞4（MHRA method ）. ADEs were counted and classified by using the preferred system organ class （SOC）and preferred term （PT）of Medical Dictionary for Regulatory Activities （MedDRA）. RESULTS & CONCLUSIONS：A total of 3 529 ADE reports with belimumab as the primary suspicious drug were screened ，in which female patients（90.31％）were much more than male patients （6.15％）；age distribution was concentrated in 18-59 years old （41.80％）. There were 1 234 cases（34.97％）of severe ADE reports ，mainly involving hospital or prolonged hospital stay. Most of the reporters were consumers or other non-medical professionals （81.84％）. North America reported the most （70.39％）and the main reporting country was the United States （2 029 reports）. A total of 180 PTs were mined from 3 529 reports，in addition to PTs associated with primary disease （systemic lupus erythematosus ，pain，arthralgia，pyrexia，weight decreased ，swelling，oropharyngeal pain ， etc.），PTs related to medication error （product dose omission ，inappropriate schedule of product administration ，underdose， product availability issue ，etc.）and PTs related to infection （influenza，urinary tract infection ，infection，sinusitis，etc.）were reported in a large number of cases. Twenty-six SOCs were involved ，the top 10 SOC in ADE reports were all kinds of injuries ， poisoning and surgical complications （2 225 reports），infections and infectious diseases （1 247 reports），general disorders and administration site conditions （1 196 reports），musculoskeletal and connective tissue disorders （1 195 reports），surgical and medical procedures（515 reports），etc. PTs in SOC in the first place （all kinds of injuries ，poisoning and surgical complications ）of ADE reports were all related to medication error ；herpes zoster ，kidney infection and cellulitis in SOC in the second place （infections and infectious diseases ）of ADE reports were not included in the drug instruction of belimumab ；most PTs in SOCs such as various nervous system diseases ，immune system diseases ，mental diseases ，benign，malignant and unknown tumors （including cystic and polypoid）which were taken attention in clinic were not included in the drug instruction of belimumab. It is suggested to avoid medication errors as far as possible in clinical use of belimumab ，and to guard against adverse reactions such as herpes zoster ， kidney infection ，cellulitis and various nervous system diseases ，immune system diseases and mental diseases. In addition ，the patients with malignant tumor or related history should use belizumab carefully.

Effect of Exercise on Expression of NeuN and SynapsinI in Cortex and Cognitive Function in Rats after Cerebral Ischemia-reperfusion / 中国康复理论与实践

Objective:To observe the effect of exercise on cognitive function and the expression of NeuN and SynapsinI in prefrontal cortex of rats after cerebral ischemia-reperfusion. Methods:Forty health male Sprague-Dawley rats were randomly divided into sham group (S group, n = 10), model group (M group, n = 10), sham & exercise group (SE group, n = 10) and model & exercise group (ME group, n = 10). The left middle cerebral artery was occluded for one hour and reperfused. SE and ME groups accepted treadmill training, for 14 days. The cognitive function of rats was evaluated with open field experiment and new object recognition experiment. The number and distribution of nerve cells in rat brain were observed with Nissl staining and immunofluorescence staining. The SynapsinI expression in serum was detected with ELISA. Results:Compared with S group, the activity, times of crossing, length and activity time in central area of open field experiment decreased in M group, as well as the cognitive index and length of new object recognition experiment (P < 0.05). Compared with M group, all the indexes increased in ME group (P < 0.05). The number of Nissl bodies decreased in M group (P < 0.05) and the arrangement was disordered, while the number of Nissl bodies increased in ME group (P < 0.05) compared with M group. The NeuN positive cells was more in S group than in M group (P < 0.05), and it was more in ME group than in M group (P < 0.05); as well as that of SynapsinI. The expression of SynapsinI decreased in M group (P < 0.05), and increased in ME group (P < 0.05). Most results of behavioral experiments positively correlated with the expression of Nissl, NeuN and SynapsinI (r > 0.221, P < 0.05). Conclusion:Cerebral ischemia-reperfusion can cause cognitive impairment in rats. Exercise can alleviate nerve injury and improve cognitive function, which may relate to promoting the expression of NeuN and SynapsinI in prefrontal cortex, to increase the number of neurons and synapses.

Exploration of omics mechanism and drug prediction of coronavirus-induced heart failure based on clinical bioinformatics / 中华心血管病杂志

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.

The relationship between the retinal macular hemorrhage and refractive abnormalities in high-rask neonates / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the relationship between the macular hemorrhage and refractive abnormalities,and analyze the occurrence probability and the factors of refractive abnormalities in high-risk neonates. <p>METHODS: From January 2017 to January 2018, a total of 1 229 neonates with high-risk factors invided into 3 groups, according to the different parts of retinal hemorrhage, examined by RetCamⅢ device. All the subjects were checked the refractive status by autorefractor when they were 1 to 1.5 years old. The abnormalities were checked their refractive status under using of 1% atropine oculentum after 7d. The relationship between the macular hemorrhage and refractive abnormalities, and the occurrence probability and the factors of refractive abnormalities were analyzed.<p>RESULTS: Among 205 eyes which were retinal hemorrhage irrelated macula 6 eyes had refractive abnormality(2.93%)in group A. 57 eyes which were macular hemorrhage 17 eyes had refractive abnormality(29.82%)in group B. 2 196 eyes which were no retinal hemorrhage 40 eyes had refractive abnormality(1.82%)in group C. It had significant difference between groups A and B, groups B and C(<i>P</i><0.001), but had no significant difference between groups A and C(<i>P</i>=0.27). Multivariate Logistic regression analysis showed that macular hemorrhage and neonatal hypoxic ischemic encephalopathy were the independent risk factors for refractive status.<p>CONCLUSION: The incidence of refractive abnormality was high in macular hemorrhage. Macular hemorrhage and neonatal hypoxic ischemic encephalopathy were the independent risk factors for refractive abnormality,and we should strengthen the observation and intervention of such new-borns.

Observation on efficacy, pharmacokinetic behaviors and safety of new modified RNA oligonucleotide targeting Foxo-1 via two routes of administration / 药学学报

Foxo-1 plays an important role in development of muscle atrophy, serving as a potential target for therapeutic treatment of the disease. In this study, the Foxo-1 mRNA was targeted by a Foxo-1 specific RNA oligonucleotide modified by 2'-O-methyl and with a butanol tag at the 3'-end. To understand the in vivo significance of new modified RNA oligos, efficacy, pharmacokinetic and safety profiles of the new modified RNA oligonucleotide targeting Foxo-1 were evaluated in mice. All experimental protocols were approved by the Animal Ethics Committee of Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention. The results showed that different doses of the RNA oligonucleotide can reduce the expression of Foxo-1 in mice by two routes of administration, leading to an increase in skeletal muscle mass of the mice. The results of pharmacokinetic evaluation showed that the plasma disappearance curve for the RNA oligonucleotide could be described by a two-compartmental model. The results of safety evaluation showed that no obvious adverse effects on renal and hepatic functions, nor on hematological parameters by intravenous or oral administration of the RNA oligo with a maximum dose of 30 mg·kg-1. Histopathology also did not reveal any significant changes in the morphology of the organs studied. In conclusion, the new modified RNA oligo is safe and effective in mice, providing experimental evidence supporting the significance for its clinical application.

Efficacy of weight adjusted bone mineral content in osteoporosis diagnosis in Chinese female population / 中华医学杂志(英文版)

BACKGROUND@#Areal bone mineral density (aBMD) applied for osteoporosis diagnosis unavoidably results in the missingdiagnosis in patients with large bones and misdiagnosis in those with small bones. Therefore, we try to find a new adjusted index of bone mineral content (BMC) to make up shortcomings of aBMD in osteoporosis diagnosis.@*METHODS@#In this multi-center epidemiological study, BMC and aBMD of lumbar spines (n = 5510) and proximal femurs (n = 4710) were measured with dual energy X-ray absorptiometry (DXA). We analyzed the correlation between the bone mass and body weight in all subjects including four age groups (50 years). And then the body weight was used for standardizing BMC (named wBMC) and applied for the epidemiological analysis of osteoporosis.@*RESULTS@#The correlation of body weight and BMC is 0.839 to 0.931 of lumbar vertebra 1-4 (L1-4), and 0.71 to 0.95 of femoral neck in different age groups. When aBMD was applied for diagnosing osteoporosis, the prevalence was 7.55%, 16.39%, and 25.83% in patients with a high, intermediate, and low body weight respectively. However, the prevalence was 21.8%, 18.03%, and 11.64% by wBMC applied for diagnosing osteoporosis. Moreover, the prevalence of osteoporosis increased by 3.76% by wBMC with the body weight increased by 5 kg. The prevalence decreased by 1.94% when the body weight decreased by 5 kg.@*CONCLUSIONS@#wBMC can reduce the missed diagnosis in patients with large body weight and reduce misdiagnosis in those with small body weight. Including children, wBMC may be feasible for osteoporosis diagnosis individuals at any age.

Measurement of the tibial alignment after total knee replacement without the extramedullary cutting guide / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the accuracy and analysis of the influencing factors of the tibia prosthetic coronal alignment after total knee arthroplasty without tibia extramedullary cutting guide.@*METHODS@#In the study, 76 patients (96 knees) who had primary total knee arthroplasty in Peking University First Hospital from February 2012 to April 2016 were selected retrospectively. All of the cases were performed by the same experienced orthopedic surgeon team. The patients were divided into 2 groups randomly: tibia cutting without guide group and tibia cutting with extramedullary guide group. Lower extremity standard anterior and posterior X-ray films of the knees were taken before and after surgery, and the anatomical tibial angle (AT), the posterior slope angle (PSA) before and after surgery, the tibia component angle (TCA) were measured in the X-ray films. We also recorded the beginning and finishing time of the operation, the operation sequence of the day respectively at the same time. The data were analyzed by correlation analysis, t test and chi square test between the two groups.@*RESULTS@#The age, gender, body mass index, AT/PSA before the surgery and TCA/PSA after the surgery of the two groups were no significant differences (P>0.05). The rate of 90-TCA≥ 3° was 31.5% (17 knees) and 31% (12 knees) respectively, there were no significant differences (P=0.956) between the two groups. The postoperative TCA of two groups was not correlated with age, gender, body mass index (BMI), operation side (P>0.05), there was also no correlation between the postoperative TCA and the start time of the operation, the whole operation time, and the operation sequence of the day (P>0.05). The two groups were divided into subgroups according to 90-AT before the operation (0°≤90-AT<3°, 3°≤90-AT<5°, 5°≤90-AT<8°, 90-AT≥8°), and there was no difference among them. But we found there was a much higher rate of 90-TCA<3° in the group without cutting guide than the group with extramedullary guide when 90-AT≥8° before the surgery (the rates were 71.4 % and 42.9%, P<0.05).@*CONCLUSION@#There is no significant difference of the tibia prosthetic coronal alignment accuracy between the tibia cutting without guide and the traditional extramedullary guided bone cutting by experienced surgeons. Only if when patients already have suffered severe malformation of knee joint (90-AT≥8°) before the operation, tibia cutting without cutting guide is more effective to rectify the tibia prosthetic coronal alignment.

Stereotactic hematoma aspiration for supratentorial hypertensive intracerebral hemorrhage:comparison with conservative treatment / 国际脑血管病杂志

Objective To compare the effectiveness of stereotactic hematoma aspiration and conservative treatment for supratentorial hypertensive intracerebral hemorrhage (HICH) with hematoma volume 25-40 ml. Methods Patients with supratentorial HICH admitted to the Department of Neurosurgery, the Fifth Affiliated Hospital of Zhengzhou University from January 2014 to January 2017 were retrospectively enrolled. The incidence of rebleeding, good outcome (defined as the modified Rankin Scale score 0-2 at 3 months after onset) rate, and mortality were compared between the stereotactic hematoma aspiration group and the conservative treatment group. Results A total of 204 patients were enrolled. Their mean age was 61. 3 ±9. 2 years, 114 were males, and their median hematoma volume was 32 ml (interquartile range 25- 39 ml), median baseline Glasgow Coma Scale score was 11 (interquartile range 9-14), and there was no patient with brain herniation. One hundred and twenty patients (58. 8％) underwent stereotactic hematoma aspiration and 84 (41. 2％) received conservative treatment. Compared with the conservative treatment group, the incidence of rebleeding in the stereotactic hematoma aspiration group was significantly lower (2. 5％ vs. 22. 6％, χ2 =20. 788, P < 0. 001), and the rate of good outcome was significantly higher at 3 months after onset (85. 0％ vs. 70. 2％; χ2 = 8. 305, P = 0. 004 ), but there was no significant difference in mortality (5. 0％ vs. 11. 9％, χ2 =3. 259, P =0. 071). Multivariable logistic regression analysis showed that advanced age (odds ratio [OR] 1. 77, 95％ confidence interval [CI] 1. 25-2. 46; P = 0. 006), previous stroke history (OR 1. 36, 95％ CI 1. 12-1. 64; P =0. 032), and conservative treatment (OR 1. 42, 95％ CI 1. 25-1. 78; P = 0. 021) were the independent risk factors for poor outcomes. Conclusions Stereotactic hematoma aspiration can significantly reduce the incidences of rebleeding and risk of the poor outcome in the supratentorial HICH patients with hematoma volume 25-40 ml. Therefore, early active surgical treatment should be considered.

Postoperative epileptic recurrence in patients with glioma-related epilepsy: Clinical characteristics and risk factors / 医学研究生学报

Objective Few studies are reported on the clinical characteristics of glioma-related epilepsy (GRE).Postoperative recurrence of epilepsy in some patients seriously affects their recovery.We aimed to explore the duration, frequency and type of the epileptic seizure as well as possible factors for postoperative recurrence of epilepsy.Methods We recorded the frequency and duration of epileptic seizures, analyzed the recurrence-related factors using the Cox regression model, and investigated the risk factors of recurrent epilepsy.Results The postoperative recurrence of epilepsy was found in 24 (26.97%) of the 89 cases, which, compared with the 65 non-recurrence cases, had a significantly longer seizure duration (7[3-10] vs 5[2-9] min, P2 cm) (HR=2.867, 95% CI: 1.210-6.795), brain wave type (HR=2.501, 95% CI: 1.058-5.914), and preoperative frequency of epileptic seizure (>6 times/mo) (HR=5.100, 95% CI: 2.437-10.677).Conclusion Postoperative recurrence of epilepsy is associated with the clinical pathological parameters, and the changes of the frequency and duration of epileptic seizures before and after surgery may provide some new theoretical reference for the treatment and prognosis of the disease.

Application of Rectal Endoscopic Ultrasonography in Recto-vaginal Endometriosis Diagnosis / 中国医科大学学报

Objective To evaluate the diagnostic value of rectal endoscopic ultrasonography for recto-vaginal endometriosis (RVEM).Methods The clinical data of 36 patients who met the criteria for RVEM between September 2009 and September 2016 in Shengjing Hospital were analyzed.Rectal endoscopic ultrasonography was compared with colonoscopy and pelvic magnetic resonance imaging (MRI) in terms of preoperative diagnosis and their conformance with surgical and postoperative pathological findings.Results Rectal endoscopic ultrasonography was superior to colonoscopy and pelvic MRI in diagnosing RVEM,invasive bowel disease,and the invasive level in the preoperative assessment (P ＜ 0.05),and in its conformance with surgical and postoperative pathological findings.Conclusion Rectal endoscopic ulwasonography is a reliable technique for diagnosing RVEM,with good accuracy in the preoperative diagnosis of invasive bowel disease and its level of invasiveness.

Analysis of postoperative efficacy and the influencing factors of the recurrence of epilepsy in Glioma-related Epilepsy / 中国神经精神疾病杂志

Objective To explore the postoperative recovery of the patients with glioma-related epilepsy and the possible risk factors for recurrence of epilepsy.Methods To collect clinical data of 89 patients with glioma-related epilepsy,we recorded Engle grade score of all patients underwent resection of tumor and seizure focus in a week,1,3 and 6 month after surgery Repeated measures ANOVA was used to analysis the difference within group.Kaplan-Meier method and Cox regression analysis were used to analysis seizure recurrence risk curve and the epileptic recurrence related factors,respectively.Results The postoperative recurrence rate was 26.97％ (24/89).Engle grade scores were 2.966±0.081.2.202±0.080,1.730±0.093 and 1.313±0.042 in a week,1,3 and 6 month after surgery.The difference was statistically significant (Ftime=96.076,P=0.000).Cox regression model showed that tumor accumulation site (RR =2.908,CI:1.083 ～7.806),postoperative edema formation (RR =4.769,CI:1.737 ～ 13.096),tumor relapse (RR=8.309,CI:3.379～20.432)were the important risk factors for recurrence epileptic seizures (all P＜ 0.05).Conclusions Surgical treatment can significantly reduce or even eliminate seizures postoperative and its long term efficacy is superior to short term efficacy.Appropriate measures should be taken to treat risk factors associated with recurrence epileptiform seizure to improve the prognosis of patients quality of life.

Influence of down-regulation of RAGE receptor on HMGB1 expression and the volume of transplanted tumor / 实用医学杂志

Objective To explore the down-regulation of advanced receptor for advanced glycation end products(RAGE)on expression of high mobility group protein B1(HMGB1)in glioma cells line and the volume change of transplanted tumor in nude mice. Methods HMGB1 expression in glioma LN229 cells line (divided into a control group and a study group) was observed by immunohistochemical assay and Western blot. The control group received normal saline,whereas the study group received RAGE receptor blocking agent FPS-ZM1. Expression of HMGB1 protein was detected by the same methods. The difference of the expression was examined by independent sample t test. 30 Nu/Nu nude mice were randomly divided into two groups;the above two kinds cell lines were injected into the same area of the left back of nude mice. Six weeks after injection ,the volume size was measured six times ,and the variance of repeated measurement data was used to analyze the difference of the volume change. Results HMGB1 protein was mainly expressed in the cytoplasm and nucleus. As compared with the control group,HMGB1 protein expression levels were decreased in the study group(P < 0.05),the growth rate of transplanted tumor in nude mice was significantly faster in the control group than in the study group ,the difference was statistically significant(P < 0.05). Conclusions The growth and invasion of HMGB1 protein may be involved in glioma by RAGE receptor. RAGE receptor blocker FPS-ZM1 can significantly reduce the expression of HMGB1 protein and inhibit the growth of transplanted tumor volume. It is expected to be used for the research on glioma cell apoptosis.

Influencing factors of seizures in glioma patients and its relationship with recurrent epilepsy / 国际外科学杂志

Objective To analyze the influencing factors of epilepsy in patients with glioma,and to explore the relationship between the epileptic factors and the recurrence of epilepsy after surgery.Methods From January 2012 to December 2015,clinical data of 95 glioma patients in the Fifth Affiliated Hospital of Zhengzhou University were retrospectively analyzed,which were divided into two groups,including 54 cases with epilepsy and 41 cases without epilepsy,all patients were underwent tumor resection,to search and resect epilepsy lesions in patients with epilepsy,Follow-up using outpatient examination and telephone interview was performed to record seizure recurrence after operation,sort and analyze the clinical data of patients,to investigate the influencing factors of epileptic seizures,and the relationship between the factors associated with epileptic seizures and postoperative recurrence of epilepsy.The epileptogenic factors were analyzed using x2 test and multifactor Logistic regression model,epileptogenic factors and recurrent epilepsy after operation were analyzed usingx2 test.Results Logistic regression model showed that peritumoral edema ＞ 2 cm(OR =6.905,95％ CI:2.787-17.106),low tumor pathological grade (0R =5.032,95％ CI:1.696-14.931) were independent risk factors for epileptic seizures;Follow-up situations:16 cases (13 cases of epilepsy group,3 cases of no epilepsy group) showed epileptic seizure in different time after the operation,preoperative epilepsy history,peritumoral edema were related to the recurrence of epileptic seizures in epilepsy group and the patients without epilepsy (x2 =2.940,3.049,all P ＜ 0.05),the pathological grade was related to the recurrence of epileptic seizures in epilepsy group (x2=4.774,P ＜ 0.05),however,it was not associated with the patients without epilepsy (x2 =0.060,P ＞ 0.05),and there was a correlation between the preoperative history of epilepsy and the postoperative recurrent seizures (x2 =4.672,P ＜ 0.05).Conclusions Peritumoral edema ＞ 2 cm and low tumor pathological grade are the factors that lead to epileptic seizures and postoperation epilepsy recurrence in glioma patients.It's expected to take some positive treatment to reduce epileptic seizures,we should pay special attention to glioma patients with epilepsy.

Therapeutic effect of endoscopic retrograde biliary drainage and nasal biliary drainage for hilar cholangiocarcinoma / 中华消化内镜杂志

Objective To evaluate the clinical effect of endoscopic retrograde biliary drainage (ERBD) and endoscopic naso-biliary drainage (ENBD) on hilar cholangiocarcinoma (HACC).Methods The clinical data of 87 patients with HACC,who underwent ERBD and ENBD form January 2010 to January 2016,were retrospectively analyzed.The incidence of postoperative severe cholangitis,biliary obstruction again within 4 weeks,reduction of total bilirubin and survival time were studied.Results There were significant differences between ERBD group and ENBD group on the incidence of severe cholangitis[29.2％ (14/48) VS 10.3％ (4/39),x2 =4.689,P=0.030] and bile duct obstruction in 4 weeks after operation [47.9％ (23/48) VS 23.1％ (9/39),x2=5.710,P =0.017].The total bilirubin within 2 weeks and 4 weeks postoperatively was significantly reduced compared with that before operation (P＜0.05).There was no statistical difference in descend range of total bilirubin between the two groups.There was significant difference between ERBD group and ENBD group in the median survival time [14 weeks (range,0-60 weeks) VS 34 weeks (range,2-96 weeks),x2 =10.101,P=0.010].Conclusion Compared to ERBD,ENBD has certain advantages on palliative care for HACC.

Microdissection testicular sperm extraction for patients with nonmosaic Klinefelter syndrome: A report of 143 cases / 中华男科学杂志

Objective@#To investigate the clinical application and outcomes of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS).@*METHODS@#A total of 143 nonmosaic KS patients underwent micro-TESE in the Center of Reproductive Medicine of Peking University Third Hospital between July 2012 and August 2016. We analyzed their clinical and follow-up data and evaluated the outcomes.@*RESULTS@#Spermatozoa were successfully retrieved from the testicular tissue in 44.76% (64/143) of the patients, 84.4% (54/64) by unilateral and 15.6% (10/64) by bilateral micro-TESE. Seventy-five of the KS patients were followed up in the years of 2014 and 2015. Of the 34 patients with successful sperm retrieval, 73.52% (25/34) achieved clinical pregnancy and 8 boys and 8 girls were already born in 14 of the 25 cases.@*CONCLUSIONS@#The micro-TESE is a useful method for sperm retrieval in nonmosaic KS patients, with high rates of sperm retrieval, clinical pregnancy, and birth of biological offspring.

Impact of the CFTR chloride channel on the cytoskeleton of mouse Sertoli cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.</p><p><b>METHODS</b>TM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.</p><p><b>RESULTS</b>CFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.</p><p><b>CONCLUSION</b>The CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.</p>