Drug-induced nephrotoxicity is very common in both new drug development and clinic practice. Various drugs can induce kidney injuries, including tubulointerstitial, glomerular and renal vascular disease. To investigate the mechanism of drug induced nephrotoxicity is important for risk reduction of new drug development, reasonable drug usage, early discovery and effective prevention/treatment of adverse effects in clinics.

ObjectiveTo systematically review the efficacy and safety of endoscopic papillary large balloon dilation (EPLBD) versus endoscopic sphincterotomy combined with large balloon dilation (ESBD) in the treatment of large common bile duct stones (≥10 mm). MethodsPubmed, Embase, Cochrane Library, CNKI, Wanfang Data, and VIP were searched for related articles published up to March 2020. Two reviewers independently performed article screening, data extraction, and quality assessment, and RevMan 5.3 software was used for statistical analysis. ResultsA total of 11 studies (6 randomized controlled trials and 5 non-randomized controlled trials) were included, with 1282 patients in total. The meta-analysis showed that in the 6 randomized controlled trials, there were no significant differences between the EPLBD group and the ESBD group in initial stone clearance rate (odds ratio ［OR］=0.71, 95% confidence interval ［CI］: 0.45-1.12, P=0.14), overall stone clearance rate (OR=1.39, 95%CI: 0.65-2.96, P=0.39), rate of use of mechanical lithotripsy (OR=1.19, 95%CI: 0.75-1.89, P=0.46), and incidence rate of early complications (OR=1.10, 95%CI: 0.60-2.03, P=075); in the 5 non-randomized controlled trials, there were no significant differences between the EPLBD group and the ESBD group in initial stone clearance rate (OR=0.64, 95%CI: 0.35-1.15, P=0.13), overall stone clearance rate (OR=0.46, 95%CI: 0.19-112, P=009), and incidence rate of early complications (OR=1.20, 95%CI: 0.65-2.21, P=0.56), but the EPLBD group had a significantly higher rate of use of mechanical lithotripsy than the ESBD group (OR=1.96, 95%CI: 1.26-3.05, P=0.003). ConclusionEPLBD and ESBD have similar efficacy and safety in the treatment of large common bile duct stones, while EPLBD may increase the risk of the use of mechanical lithotripsy. More high-quality randomized controlled trials are needed to confirm this conclusion.

Objective To investigate the effect of antisense oligonucleotides of miRNA-34a on non-small cell lung cancer (NSCLC) and its molecular mechanism.Methods The expression of miRNA34a in human non-small cell lung cancer cell line HCC827 and human normal lung cell MRC-5 was detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR).HCC827 cells were divided into three groups:blank control group,negative control group,anti-sense oligonucleotide group (liposome 2000 transfected anti-sense oligonucleotide miRNA-34a);cell counting kit-8 (CCK-8) method was used to detect cell proliferation,Jimsa staining was used to detect cell cloning ability,Transwell test was used to detect cell migration and invasion ability;RT-PCR and Western blot were used to detect phosphatase and tensin homolog (PTEN),phosphorylation-protein kinase B (p-Akt),phosphatidylinositol-3-kinase (PI3K)mRNA and protein expression.Results The relative expression of miRNA34a in HCC827 cells was significantly higher than that in human normal lung cells (P ＜ 0.01).The relative expression of miRNA34a in antisense oligonucleotide miRNA-34a group was significantly lower than that of negative control group and blank control group (P ＜ 0.05),and there was no significant difference between negative control group and blank control group (P ＞ 0.05).At 48 h,72 h and 96 h,the proliferation level of HCC827 cells in antisense oligonucleotide miRNA-34a group was significantly lower than that in negative control group and blank control group (P ＜ 0.05).The cell cloning rate of antisense oligonucleotide miRNA-34a group was significantly lower than that of negative control group and blank control group (P ＜ 0.01).The number of migration and invasion of HCC827 cells in antisense oligonucleotide RNA-34a group was significantly lower than that in negative control group and blank control group (P ＜0.01).The relative expression of PTEN mRNA and protein in antisense oligonucleotide miRNA-34a group was significantly higher than that in negative control group and blank control group (P ＜ 0.05);the relative expression of p-Akt,PI3K mRNA and protein in antisense oligonucleotide miRNA-34a group were significantly lower than that in negative control group and blank control group (P ＜ 0.05).Conclusions The expression level of miRNA-34a in human nonsmall cell lung cancer cells is significantly higher than that in human normal lung cells.Antisense oligonucleotides of miRNA-34a can inhibit the proliferation,cloning,migration and invasion of human non-small cell lung cancer cells.The mechanism may be related to the negative regulation of PTEN/p-Akt/PI3K signaling pathway.

Objective:To study the effectiveness and safety of perioperative lactated Ringer solution (LRS) in prevention and alleviation of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) under different fluid replacement regimens to arrive at the most precise quantitative fluid replacement regimen.Methods:Pubmed, Embase, Cochrane Library Database, Wanfang Database, CNKI, and VIP were searched from inception to February 2020. Randomized controlled trials on LRS in prevention and alleviation of PEP under different fluid replacement regimens were collected. The experiment group was actively rehydrated with LRS during the perioperative period, and the amount of rehydration was significantly higher than that of the control group. The control group was given standard dose of LRS or normal saline. Two researchers independently selected the articles based on predetermined inclusion and exclusion criteria, extracted the data, and evaluated the risk of bias. RevMan 5.3 software was used for statistical analysis.Results:Ten studies with 2 261 patients were included, with 1 140 patients in the experiment group, and 1 121 patients in the control group. Meta-analysis showed that when the experiment group was given LRS at a rate of 5.0 ml·kg -1·h -1 during the perioperative period for about 9 hours and compared with the control group, the incidence of PEP in the experiment group was significantly reduced ( OR=0.32, 95% CI: 0.21-0.48, P<0.05). The incidence of moderate to severe PEP was also significantly reduced ( OR=0.28, 95% CI: 0.09-0.84, P<0.05). There was no increase in the incidence of adverse reactions related to fluid replacement. However, there were no significant differences in the incidence of PEP, and in moderate to severe PEP between the two groups when LRS was given at a rate of 4.0~4.5 ml·kg -1·h -1 within 9 hours, and less than 4.0 ml·kg -1·h -1 within 24 hours of total rehydration time (all P>0.05). Conclusion:During the perioperative period, the current evidence showed that it is most reasonable to give the fluid replacement regimen with aggressive hydration using LRS at a rate of 5.0 ml·kg -1·h -1 in about 9 hours to prevent and alleviate PEP. This is recommended for clinical practice and is worthy of further future studies.

Objective:To study the relationship between pancreaticobiliary maljunction (PBM) with cholangiopancreatic diseases, and to evaluate the efficacy and safety using endoscopic therapy for PBM.Methods:The clinical data of 734 patients treated with ERCP at the Affiliated Hospital of Guizhou Medical University from May 2016 to April 2020 were analyzed retrospectively. Of 31 PBM patients who were finally included in this study, there were 23 patients with benign diseases and 8 patients with malignant diseases. Using the diameter of bile duct, these patients were divided into two groups: dilated bile duct group and the non-dilated bile duct group. The general characteristics of patients, incidences of cholangiopancreatic disease, endoscopic treatment, therapeutic efficacy and follow-up data were analyzed.Results:Of the 31 patients with PBM, 11 were males and 20 were females, aged (56.7±16.2) years. There were 4 patients with choledochal cyst (12.9%) and 6 patients with biliary cancer (19.4%). The incidences were significantly higher than those in non-PBM patients (0.9% and 5.3%, respectively, P<0.05). All 31 patients with PBM underwent endoscopic EST treatment, including 15 patients (48.4%) treated with endoscopic naso-biliary drainage (ENBD), 9 patients (29.0%) with endoscopic retrograde biliary drainage (ERBD), 4 patients (12.9%) with endoscopic papillary balloon dilatation (EPBD)+ ENBD, 1 patient (3.2%) with endoscopic metal biliary endoprothesis (EMBE)+ ENBD, 1 patient with ERBD+ endoscopic retrograde pancreatic drainage (3.2%), and 1 patient with EPBD+ ERBD+ EMBE (3.2%). The operative success rate was 100%. Serum AST, ALT, ALP, GGT, TBil and DBil levels of patients in the benign group and malignant group were significantly decreased postoperatively when compared with the preoperative levels (all P<0.05). One patient (3.2%) developed post ERCP pancreatitis. The preoperative and postoperative NRS scores of the patients in the benign group were 7(6, 8) points compared to 0 (0, 1) points, respectively ( P<0.05). All the 23 patients in the benign group were followed up for (25.13±12.90) months. There were no patients who were loss to follow-up. There was no malignant transformation. Three PMB patients with dilated bile ducts still had attacks of abdominal pain or jaundice. The symptoms of the remaining 20 patients were completely relieved, giving a treatment efficacious rate of 87.0% (20/23). Conclusions:PBM was closely related to choledochal cysts, biliary cancer and other diseases. Endoscopic treatment was efficacious and safe, and provided a safe and feasible treatment in preventing future cholangiopancreatic attacks.

Objective:To investigate the behavioral, electroencephalographic, and cognitive functional differences in drug-resistant epileptic rat models of cognitive impairment prepared by intraperitoneal injection of lithium chloride-pilocarpine followed by intracranial injection of pilocarpine or carbamylcholine.Methods:One hundred and sixty adult male SD rats were randomly divided into normal control group ( n=10), lithium chloride-pilocarpine group (establishing epileptic rat models by intraperitoneal injection of lithium chloride-pilocarpine, n=50), pilocarpine-pilocarpine group (intracranial injection of pilocarpine after intraperitoneal injection of lithium chloride-pilocarpine, n=50)and pilocarpine-carbamylcholine group (intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine, n=50). Frequency and duration of spontaneously recurrent seizures (SRSs) were observed by video monitoring system, and 2 weeks after that, phenobarbital and phenytoin sodium were injected intraperitoneally to screen drug-resistant models. Frequency and amplitude of the epileptic waves in EEG were recorded by BL-420 Bio-signal Acquisition and Processing System. Novel object recognition experiment was used to detect the novel exploration, Y-maze free exploration experiment and new and different arm experiment were used to detect the spatial recognition and memory ability, and Morris water maze experiment was used to detect the spatial memory ability. Results:(1) Twenty-four rats (48.00%) survived in the lithium chloride-pilocarpine group, 25 (78.00%) in the pilocarpine-pilocarpine group, and 21 (65.62%) in the pilocarpine-carbamylcholine group; and ultimately 7, 9, and 8 drug-resistant epileptic rat models were identified, respectively; frequency and duration of SRSs in the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group were significantly higher/longer than those in the lithium chloride-pilocarpine group ( P<0.05). (2) The pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly higher amplitude of the epileptic waves in EEG compared with the lithium chloride-pilocarpine group ( P<0.05); the frequency of the epileptic waves in EEG increased gradually in the lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group ( P<0.05). (3) Discrimination index, accuracy, ratio of distance traveled in novel arm to total distance, and time of novel arm entries gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). (4) Compared with the normal control group, the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly decreased frequency in crossing the original platform ( P<0.05); compared with the normal control group, lithium-pilocarpine chloride group and pilocarpine-pilocarpine group, the pilocarpine-carbamylcholine group had statistically shorter distance of target quadrant activity ( P<0.05); number of entries in the target quadrant gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). Conclusion:Drug-resistant epileptic rat models established by intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine have high survival rate, high SRSs rate, and severe cognitive impairment, which is suitable for studying drug-resistant epilepsy combined with cognitive impairment.

Objective:To explore the application value of ventricular intracranial pressure monitoring (V-ICPM) in the treatment of unilateral temporal lobe cerebral contusion.Methods:A retrospective cohort study was conducted to analyze the clinical data of 295 patients with unilateral temporal lobe cerebral contusion admitted to 904th Hospital of PLA Joint Support Force from January 2014 to August 2021, including 172 males and 123 females; aged 14-78 years [(46.3±14.7)years]. V-ICPM was used in 136 patients (V-ICPM group), who received surgical or non-surgical treatment according to the monitoring, while not in 159 patients (non-V-ICPM group), who received routine surgery or non-surgical treatment. The two groups were compared in terms of the rates of intracranial hematoma clearance by craniotomy, decompressive craniectomy (DC) and dehydration and osmotic therapy during hospitalization, use time of 20% mass fraction of mannitol and 30 g/L hypertonic salt, displacement rate of brain midline structure of head CT≥10 mm after discharge, rate of intracranial infection, hydrocephalus and epilepsy, and Glasgow Outcome Scale (GOS) at 6 months after discharge.Results:All patients were followed up for 6-12 months [(8.9±2.1)months]. During hospitalization, the rate of intracranial hematoma clearance by craniotomy and the rate of DC in V-ICPM group were 35.3% (48/136) and 8.1% (11/136), lower than 47.2% (75/159) and 22.0% (35/159) in non-V-ICPM group ( P<0.05 or 0.01). There was no significant difference between the two groups in the rate of dehydration and osmotic therapy or the use time of mannitol (all P>0.05). The use time of hypertonic salt in V-ICPM group was (7.2±2.5)days, more than (4.1±1.8)days in non-V-ICPM group ( P<0.05). After discharge, the displacement rate of brain midline structure of head CT in V-ICPM group was 29.4% (40/136), lower than 42.8% (68/159) in non-V-ICPM group ( P<0.05). There was no significant difference between the two groups in the rate of intracranial infection, hydrocephalus and epilepsy (all P>0.05). Six months after discharge, the good rate of GOS in V-ICPM group was 91.2% (124/136), significantly better than 81.8% (130/159) in non-V-ICPM group ( P<0.05). Conclusion:For unilateral temporal lobe cerebral contusion, V-ICPM is associated with reduced rate of craniotomy exploration and DC, decreased incidence of complications and improved prognosis of the patients in spite of longer use time of hypertonic salt.

OBJECTIVE To provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients. METHODS The data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022， such as oncology department， radiotherapy department， gynecology department， and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically， and the irrational use of antiemetic drugs was analyzed. RESULTS A total of 520 patients were included， involving 248 （47.69%） using chemotherapy drugs with a moderate emetogenic risk level and 135 （25.96%） with a high emetogenic risk level. A total of 461 cases （73.06%） of 5-hydroxytryptamine 3-receptor antagonists were used， including palonosetron in 333 cases， ondansetron in 106 cases， tropisetron in 15 cases and granisetron in 7 cases， and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines （32.10%）. Neurokinin-1 receptor antagonists were used in 170 cases （26.94%）， including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients （31.15%）； among the types of irrational drugs， the antiemetic regimen was unreasonable in the largest number of cases （22.40%）， followed by the irrational pharmacoeconomics （19.13%）. CONCLUSIONS The emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high， and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians， nurses， pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs， reasonably select antiemetic drugs based on emetogenicity rating， and improve the compliance of doctors with the guidelines to ensure the safety， effectiveness， and cost-effective of patient medication.