Systematic evaluation of the efficacy and safety of intravenous human immunoglobulin combined with cyclophosphamide in the treatment of systemic lupus erythematosus / 中国药房

OBJECTIVE To systematically evaluate the safety and effectiveness of intravenous human immunoglobulin （IVIG） combined with cyclophosphamide in the treatment of systemic lupus erythematosus （SLE）， and to provide an evidence-based basis for clinical medication. METHODS Retrieved from PubMed， Embase， Cochrane Library， CBM， CNKI and Wanfang database， randomized controlled trials （RCTs） about IVIG combined with cyclophosphamide versus cyclophosphamide alone based on glucocorticoids were collected. The quality of the included literature was evaluated with Cochrane 5.1.0 risk of bias assessment tool after literature screening and data extraction， and meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 13 RCTs were included， involving 842 patients. Meta-analysis showed that compared with cyclophosphamide alone， IVIG combined with cyclophosphamide improved the overall response rate of systemic lupus erythematosus [RR＝1.23， 95%CI（1.15， 1.32）， P＜0.000 01]， lowered the systemic lupus erythematosus disease activity index [MD＝－2.05， 95%CI（－2.51， －1.60）， P＜0.000 01]， relieved 24 h proteinuria [MD＝－1.29， 95%CI（－1.57， －1.01）， P＜0.000 01]， reduced the inflammatory factor MCP-4 [MD＝－28.04， 95%CI（－32.72， －23.37， P＜0.000 01）]， IL-4 [MD＝－1.66， 95%CI（－1.96， －1.36）， P＜0.000 01]， and boosted immune complement C3 [SMD＝0.74，95%CI（0.34，1.14）， P＝0.000 3] and complement C4 [SMD＝0.99，95%CI （0.31，1.67）， P＝0.004]； it had similar incidence of adverse drug reactions to cyclophosphamide therapy alone [RR＝0.81， 95%CI （0.57， 1.17）， P＝0.26]. CONCLUSIONS Compared with cyclophosphamide alone， IVIG combined with cyclophosphamide has a positive role in improving the overall response rate of treating SLE， improving clinical symptoms， reducing inflammatory factors， improving immune function， but the results should be interpreted with caution.

Clinical observation of 9 cases of rituximab followed by belimumab in the treatment of severe systemic lupus erythematosus / 中国药房

OBJECTIVE To investigate the clinical efficacy and safety of rituximab （RTX） followed by belimumab （BLM） in patients with severe systemic lupus erythematosus（SSLE）. METHODS Nine SSLE patients， who were treated with RTX followed by BLM for more than 6 months in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Zhengzhou University from October 2020 to June 2021， were enrolled. Baseline clinical data of patients， laboratory examination results and basic treatment status at weeks 0， 4， 12， and 24 of medication were collected retrospectively. The patients’ systemic lupus erythematosus disease activity index （SLEDAI） score， glucocorticoid dosage and serological indicators （complement C3， complement C4， serum albumin， and 24-hour urine protein quantification） level were analyzed. At the same time， the occurrence of adverse drug reaction was collected. RESULTS All 9 patients completed more than 24 weeks of RTX followed by BLM therapy. All patients suffered from renal impairment， of which 7 （77.8%） had renal pathology support， 3（33.3%） had blood system damage and 2 （22.2%） had nervous system damage. During treatment， with the prolongation of treatment time， the SLEDAI score， 24- hour urinary protein quantification， and glucocorticoid dosage of patients showed a significant downward trend， and ultimately decreased to the normal index level （P＜0.05）； serum albumin， complement C3 and complement C4 all showed a significant upward trend， eventually rose to the normal index level （P＜0.05）. During treatment and follow-up， 1 patient developed herpes zoster， 1 patient developed upper respiratory tract virus infection， and 1 patient developed urinary system bacterial infection. All patients recovered after symptomatic treatment. CONCLUSIONS In sequential use of RTX followed by BLM for SSLE， early administration of RTX can quickly stabilizethe condition， significantly alleviate clinical symptoms， and gradually normalize specific serological indicators； subsequent administration of BLM can reduce the type and dosage of basic treatment drugs； there is no increase in the incidence of adverse drug reactions.

Analysis on research status and hot spots of gabapentinoid drugs in the treatment of pain / 中国药房

OBJECTIVE To analyze the si tuation and hot spots of gabapentinoid drugs in the treatment of pain. METHODS Related researches about gabapentinoid drugs in the treatment of pain were retrieved from Web of Science core collection database during Jan. 1st，2011-Dec. 31st，2020. VOSviewer 1.6.17，CiteSpace 5.8.R1 and Excel 2018 software were used to statistically analyze the key characteristics of relevant literature ，such as the annual publications ，countries/regions，institutions，authors， journals and research hot spots. RESULTS & CONCLUSIONS A total of 3 519 literatures were retrieved ，and the annual publication outputs showed an upward trend generally. Totally 86 countries/regions had conducted relevant studies ，of which the United States ranked first （up to 1 219），and had close cooperation with the United Kingdom ，Canada，China，Germany，Japan， etc；a total of 3 996 institutions had published relevant literatures ，and the Pfizer Inc. issued the most publications ；the most studies were devoted by Professor Parsons from the University of California San Diego ，and the highest co-citations author was Professor Gilron from the Queen ’s University. Among 1 185 journals，Pain ranked first not only in the high-productive journal ，but also in the co-cited journal. The main hot topics include abuse and misuse of gabapentinoid ，off-label use of gabapentinoid ，clinical application of gabapentinoid as a component of multimodal analgesia ，and the update of guidelines for pain based on systematic evaluation and meta-analysis.

Visualization Analysis of the Literatures on Drug-induced Kidney Injury / 中国药房

OBJECTIVE：To study the research status ，hotspots and frontier cha nges of drug-induced kidney injury （DIKI）， and to provide reference for the research of DIKI in China. METHODS ：Literatures related to DIKI published from 2001 to 2020 were retrieved from Web of Science database. CiteSpace 5.7.R2 software was used to conduct visualization analysis for DIKI related literatures from aspects of the number of publications ，authors and cited authors ，institutions，countries，related disciplines ， co-cited journals ，co-cited literatures and keywords. RESULTS ：A total of 1 320 literatures were included ，and the number of published literatures about DIKI researches showed an upward trend during 2001-2020. The most studies and the highest co-citations were devoted by the Yale University scholar Mark A Perazella （18 literatures，cited for 137 times）. There were 76 countries carrying out research in this field ，among which the United States had the first advantage （445 literatures，accounting for 34.29％ of the total number of literatures ）. A total of 2 175 institutions participated in this field ，of which Yale University contributed the most publications ；pharmacology，nephrology，toxicology and other related disciplines were involved in this field ；Kidney International（652 literatures，USA）published the most research in this field ；the most frequently cited literature was “Drug- induced nephrotoxicity ：clinical impact and preclinical in vitro models ”，published by Tiong et al in 2014. Through the keyword cluster analysis ，the research hotspots in this field mainly focused on the risk factors of DIKI ，the research of DIKI in special groups，the mechanism of DIKI related drugs ，the exploration of DIKI biomarkers ，and the preclinical research of DIKI. CONCLUSIONS：DIKI’s research has been paid more and more attention by scholars ，but the cooperation between China and other countries in this field is limited. In the future ，more attention should be paid to the research hotspot in this field and international exchanges and cooperation should be strengthened.

Establishment of a HEK-293 cell line stably expressing human TLR5and NF-κB responsive reporter / 国际药学研究杂志

Objective To construct the lentivirus plasmids of human Toll like receptor-5(TLR5)and nuclear factor(NF)-κB signaling pathway responsive luciferase and green fluorescent protein(GFP)reporters,and establish a HEK-293 cell line stably expressing human TLR5 and NF-κB responsive reporters. Methods The TLR5 and 5×NF-κB-binding sites genes were cloned to lenti?viral expressing plasmid pWSLV-puro and pWSLV-nanluc-GFP,respectively. The recombinant plasmids,pWSLV-hTLR5-puro and pWSLV-5×NF-κB-nanluc-GFP were respectively transfected with packaging plasmid into HEK293T cells in order to package lentivirus. The lentivirus was used to coinfect HEK-293 cells,and the positive clones stably expressing TLR5 and NF-κB responsive reporter (HEK293-N-T)were generated using colony-purification in present of puromycin and fluorescence activated cell sorting. The cells ex?pressing TLR5 were confirmed by Western blot and immunofluorescence. Additionally,the cells expressing NF-κB responsive reporter were confirmed by fluorescence microscopy and luciferase quantitative assay. Results The results of recombinant plasmids digestion identification and the sequencing of cDNA showed that the sequences inserted into the plasmid and the expected sequences of hTLR 5 and 5×NF-κB-binding sites genes were completely consistent. It was confirmed that the hTLR5 and 5×NF-κB-binding sites genes were correctly inserted into the vectors,and that the recombinant plasmids,pWSLV-hTLR5-puro and pWSLV-5 × NF-κB-nanluc-GFP, were successfully constructed. Additionally,Western blot and immunofluorescence analysis showed that TLR5 were stably expressed in a high level in the HEK293-N-T cells and located in the cell membranes. Moreover,the results of fluorescence microscopy and lucif?erase quantitative assay indicated that the NF-κB responsive reporter could reflect the activation of NF-κB signaling in a dose-depen?dent manner. Conclusion The HEK-293 cell line stably expressing human TLR5 and NF-κB responsive reporter has been successful?ly established and the HEK293-N-T cells can be used for the screening and evaluation of drugs target to TLR5.

Effect of Leuprolide Preoperative Used in Patients with Uterine Fibroids / 中国药师

Objective:To study the effect of leuprolide preoperative used in the patients with uterine fibroids .Methods:Totally 70 patients with uterine fibroids were divided into the observation group and the control group with 35 ones in each.The 35 patients in the control group were with laparoscopic myomectomy , and those in the observation group was given leuprolide , 3.75 mg per time, once in a month for 3 months, and then undergone laparoscopic myomectomy .The serum hormone levels , menstruation situation and fi-broids and uterus volume changes in the observation group were observed and compared before the treatment and after the 3-month leu-prolide treatment .The situation during the operation and after the operation , and the recurrence rate of uterine fibroids between the two groups were compared .Results:After the pretreatment of leuprolide , the levels of luteinizing hormone ( LH) , follicle-stimulating hor-mone (FSH) and serum estradiol (E2) in the observation group were significantly lower than those before the treatment (P<0.05), and the menstrual blood volume , uterine volume and fibroid volume were significantly lower than those before the treatment , and the differences were statistically significant (P<0.05).The blood loss during the operation and pelvic drainage of the observation group were significantly lower than those of the control group , and the ambulation time and length of hospital stay of the observation group were significantly shorter than those of the control group with statistically significant differences (P<0.05).Conclusion:Leuprolide preoperative used in the patients with uterine fibroids can significantly reduce serum hormone levels and fibroid volume , which are ben-eficial to myomectomy with smaller surgery invasion and better prognosis .

The analysis of nystagmus in patients with posterior canal benign paroxysmal positional vertigoin positioning test / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze and summarize nystagmus of patients with posterior canal benign paroxysmal positional vertigo (BPPV) in positioning test,and to improve the diagnosis and treatment of posterior canal BPPV (PSC-BPPV).@*METHOD@#The present study was conducted on 175 patients who had unilateral BPPV of the posterior semicircular canal (PSC). Their positional nystagmus recorded by videnonystagmography in Dix-Hallpike test,roll test and roll over test were analyzed to summarize the characteristics of nystagmus on nystagmograph of PSC-BP-PV.@*RESULT@#Of the 175 patients, lesion was located in the left PSC in 69 (39.4%) patients,the right PSC in 106 (60. 6%)patients. The nystagmus of patients with PSC-canalithiasis showed upward on the vertical phase of nystagmograph and orientated the different side on horizontal phase in the head hangging position. The horizontal phase pointed to the contralateral side in 47(26. 9%) patients, the ipsilateral contralateral side in 100(57. 1%) patients,no significant reverse ingredients in 28(16.0%) patients. When these patients returned to sit,139(79.4%) patients showed down beating positioning nystagmus, whereas 36 (20. 6%) patients with no nystagmus only had a short vertigo or dizziness. The horizontal phase of the 139 patients pointed to the contralateral side in 40(22. 9%) patients,the ipsilateral contralateral side in 68(38. 9%) patients,no significant reverse ingredients in 31(17. 7%) patients. In roll test,12 patients of the right PSC-BPPV presented an up-beating rotatory nystagmus when the head turned to right,and 5 patients of the left PSC-BPPV presented a down-beating rotatory nystagmus when the head turned to left. When the patients changed body from the left lateral position to the right lateral position in the roll over test, 74(42. 3%) patientsshowed vertical positioning nystagmus. In 30 patients who presented an up-beating nystagmus, there were 25(83. 3%) patientscame from the right PSC-BPPV. In 44 patients who presented a down-beating nystagmus, there were 36(81. 8%) patientscame from the left PSC-BPPV. The direction of the vertical nystagmus was highly correlated with the judgment about the side of the PSC-BPPV in roll over test (P<0. 01).@*CONCLUSION@#The patient with PSC-canalithiasis showed an uncertain direction in torsional nystagmus in Dix-Hallpike test,the diagnosis was mainly concern with the vertical nystagmus. When we found a rotatory nystagmus with much more up-beating nystagmus in roll test, it might be PSC-BPPV. We also can use the roll over test to diagnose the location of the otolith in which side of the PSC-BPPV.

The analysis of masking therapy in the early stage of the patients with noise-induced tinnitus / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the effect of masking therapy for the early stage of the patients with noise-induced tinnitus,and imply the treatment for patients with noise-induced tinnitus.@*METHOD@#Sixty-eight cases with tinnitus were studied. All the patients took the audiological examinations and tinnitus tests firstly, and accepted the masking therapy for 6 months. The therapeutic effiency was evaluated according to tinnitus handicap inventory (THI) and subjective visual-analogue scale (VAS). The minimum masking intensity was also evaluated.@*RESULT@#The majority of the patients with noise-induced tinnitus (59 cases, 86. 8%) had tinnitus frequency of 4 kHz,and most of them (44 cases, 64. 7%) had positive residual inhibition tests. Tinnitus completely disappeared in 3 cases after masking therapy, and the efficiency of this treatment is 83. 8%. There was significant difference in the scores of THI and VAS before and after therapy(P<0. 01), and there was also significant difference in the minimum masking intensity (P<0. 01).@*CONCLUSION@#Masking therapy is the most important treatment for the patients in the early stage of noise-induced tinnitus. The therapeutic effiency is significant and should be promoted.

Pin1 inhibitor juglone induces apoptosis in human cervical cancer SiHa cells / 中国病理生理杂志

AIM:To explore the effect of peptidyl-prolyl cis/trans isomerase (Pin1) inhibitor juglone on apop-tosis of human cervical cancer SiHa cells.METHODS:Cultured SiHa cells were incubated with juglone at concentrations of 10, 20, 50, 80 and 100 μmol/L for 24 h.The SiHa cell activity was detected by methyl thiazolyl tetrazolium ( MTT) assay.The cell apoptosis was analyzed by flow cytometry with Hoechst 33258 staining.The protein levels of cleaved caspase-3,8,9 and PTEN was determined by Western blotting.RESULTS:In different doses of juglone groups, the SiHa cell growth was greatly inhibited ( P<0.05) in a dose-dependent manner as compared with control group.The IC50 of ju-glone was 20.4 μmol/L.After treatment with juglone at concentration of 20 μmol/L for 12 h, the apoptosis of SiHa cells was induced, and the typical morphological changes of cell apoptosis such as karyopyknotic pyknic hyperfluorescence bolus, nuclear fragmentation and apoptotic body were observed by Hoechst 33258 staining.The early apoptotic rate was increased significantly as compared with the control.The protein levels of cleaved caspase-3, 8, 9 and PTEN were also increased sig-nificantly as compared with control group.CONCLUSION:Juglone significantly inhibits the cell activity and induces the apoptosis of SiHa cells in vitro by inhibiting the caspase pathway and increasing the expression of anti-oncogene.

An Analysis of Auditory Brainstem Response in Autistic Children of 6 Years or Younger / 听力学及言语疾病杂志

Objective To investigate the characteristics of auditory brainstem response (ABR) in autistic children of 6 years or younger .Methods A total of 98 children with normal hearing and 22 autistic children were en‐rolled in this study .They were divided into 3 groups :1~2 years age group ,20 .05) .In 80 dB nHL click sound stimulus ,there was also no statistical difference in the values of peak latencies or interpeak intervals of ABR between normal hearing children and autistic children (P> 0 .05) ,whereas ,prolongation of peak latencies or interpeak intervals of ABR occurred in 36 .36%(25 .00% ears) autistic children .The ratio of prolongation of peak latencies of I ,III ,V waves and interpeak inter‐vals of I-III ,III-V ,I-V occurred in 4 .54% ,6 .82% ,13 .64% ,18 .18% ,6 .83% and 15 .91% ,respectively . Conclusion The ABR in some autistic children present abnormality and occur in various forms with the prolongation of interpeak intervals of I -III as the most common .

Audiological Analysis of Patients with Intact Tympanic Membranes and Conductive or Mixed Hearing Loss / 听力学及言语疾病杂志

Objective To investigate audiological characteristics of patients with intact tympanic membranes and conductive or mixed hearing loss .Methods A retrospective study was carried out among 30 patients (42 ears) with intact tympanic membranes and conductive or mixed hearing loss who underwent exploratory tympanotomy . The preoperative outcomes of pure tone audiometry ,tympanometry ,resonant frequency of middle ear and temporal bone CT scan were analyzed .Results Among 42 ears ,30 ears with otosclerosis and 12 ears with ossicular chain dis-ruption were confirmed in exploratory tympanotomy ,but only 5 ears showed positive findings in CT scan .The mean thresholds of bone conduction ,air conduction and air -bone gap at frequencies of 0 .5 ,1 and 2 kHz were 27 .5 ± 1 .3 dB HL ,67 .0 ± 1 .8 dB HL ,39 .5 ± 1 .1 dB HL ,respectively .An analysis of tympanometric data of all patients re-vealed that 50% of all ears (21/42) were type A tympanograms ,42 .9% (18/42) were type As tympanograms ,and 7 .1% (3/42) were type Ad tympanograms .The mean of the resonant frequency of the middle ear in otosclerositic patients (1 079 .0 ± 67 .4 Hz) was significantly higher than ossicular chain disruption patients (633 .3 ± 43 .6 Hz) . Conclusion Otosclerosis is the most common in the patients with intact tympanic membranes and conductive or mixed hearing loss .The middle ear resonant frequency of otosclerositic patients is significantly higher than that of ossicular chain disruption patients .

Acute toxicity of diphenylchlorarsine in mice and rats / 第三军医大学学报

Objective To assess the toxicity risks of diphenylchlorarsine (DA) to environments, human beings and livestock. Methods Totally 120 mice were randomly divided into 6 groups and given DA by gastric gavage at the doses of 32, 30, 28, 26, 24, 22 mg/kg respectively for LD_(50) of DA in mice. The toxicity of DA in rat skin were evaluated by smearing 50 ?l DA at the concentrations of 140, 70, 35, 17.5, and 8.8 mg/ml to an area of 4 cm2, and that of eyes exposure was carried out by dropping 10 ?l DA of 140.7, 70, 7, 0.7 mg/ml in rat eyes. The counterpart skin area and eyes served as control. Results LD_(50) of DA in mice was 28.07 mg/kg, the estimated doses for no-observed-adverse-effect levels (NOELs) were 8.8 mg/ml (0.44 mg) to the skin and 0.7 mg/ml (0.014 mg) to the eyes respectively. Conclusion DA can induce the injuries on the liver, kidneys, esophagus and stomach. High concentration of DA can cause inflammation of the skin and lens opacification, even blind.

Effects of Perinatal Diphenylchloroarsine Chloride Exposure on Livability and Reproductive Function of F1 Generation Rats / 环境与健康杂志

Objective To study the effects of perinatal exposure of diphenylchloroarsine chloride(DA)on the livability and reproductive function of F1 generation rats.Methods The pregnant rats were treated with DA by gavage at 0(solvent control),0.63(low dose),0.94(medium dose),1.89(high dose)mg/(kg?day)from day 6 of pregnancy to day 15 of lactation.The general condition,the change of body weight and abnormity of main organs of the F0 pregnant rats and F1 young rats were observed,and the livability and abnormity of reproductive function of F1 young rats were examined.Results The results indicated that compared with the negative control,the increasing amounts of the body weights of the F0 maternal rats and the livability of F1 young rats aged 4 day significantly decreased at 0.94 mg/kg and 1.89 mg/kg,the livability in lactation period obviously reduced at 1.89 mg/kg,and the rate of absorbed fetus in F1 pregnant rats increased at 1.89 and 0.94 mg/kg.Conclusion DA exposure may have an adverse effect on livability and reproductive function of the F1 offspring when the dosage is no fewer than 0.94 mg/kg.