OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

OBJECTIVE To analyze the use of children’s drugs in public medical institutions in the Inner Mongolia Autonomous Region， and provide some reference for the rational use of children’s drugs and the improvement of children’s drug list in the whole region. METHODS The generic names， specifications， and dosage forms of children’s drugs were collected from all levels of public medical institutions in the Inner Mongolia Autonomous Region in 2023. The method of defined daily dose （DDD） and ranking ratio （B/A） were used to explore the frequency of drug use， daily average cost and cost-effectiveness of children’s drugs in this region， and the dosage forms， category， and drug use convergence of children’s drugs in medical institutions in the whole region. RESULTS In 2023， 1 751 public medical and health institutions in Inner Mongolia Autonomous Region were equipped with 267 kinds of children’s drugs， including 12 drug categories. The main dosage forms were granules， oral solutions， and syrups. The drugs that were frequently used in medical institutions at all levels were mainly antipyretic， analgesic， anti-inflammatory drugs （mostly Chinese patent medicines）， and respiratory drugs. The daily average cost of children’s drugs with the highest DDDs in tertiary， secondary， and primary public medical institutions was low， and the B/A value of most drugs with higher DDDs was around 1. However， the B/A value of some drugs was high， which may lead to overuse. The drug use convergence between primary public medical institutions and secondary/tertiary public medical institutions was less than 50%. CONCLUSIONS The types of drugs involved in children’s drugs in Inner Mongolia Autonomous Region are comprehensive and the social and economic benefits are in good synchronization， but the dosage form is single and there are few special rules and dosage forms for children. The proportions of Chinese patent medicines in primary and secondary public medical institutions are high， and the risk of drug use should be paid attention. The cohesion between children’s drugs in primary public medical institutions and higher public medical institutions is slightly poor.

Objective To discuss the safety and efficacy of arterial embolization combined with local ablation in the treatment of recurrent and refractory chest wall tumors.Methods The clinical data of 11 patients with chest wall tumor that recurred after surgery and progressed after treatment were retrospectively analyzed.On the basis of the original treatment regimen,DSA-guided arterial embolization and CT-guided local ablation were employed.VAS score of pain relief and postoperative complications were recorded,and the therapeutic efficacy was evaluated Results All the patients were follow up for a median time of 18.5 months.Successful DSA-guided arterial embolization was accomplished in all patients.Seven patients(9 lesions in total)initially received CT-guided radiofrequency ablation(RFA),and tumor reoccurred in 2 patients,who had to receive RFA once more.Four patients(5 lesions in total)initially received CT-guided microwave ablation(MWA),and tumor reoccurred in one patient,who had to receive MWA again.According to mRECIST criteria,the 6-month,12-month and 18-month objective response rates(ORR)were 72.7%(8/11),45.5%(5/11)and 18.2%(2/11)respectively,the 6-month,12-month and 18-month overall survival rates were 81.8%(9/11),63.6%(7/11)and 27.3%(3/11)respectively,with a median survival time of 13.2 months.The postoperative one-month and 3-month VAS scores were(2.42±1.25)points and(1.91±1.24)points respectively,which were strikingly lower than preoperative(6.78±1.13)points,the differences were statistically significant(P＜0.05).After surgery,3 patients developed pleural effusion,which disappeared after puncture and drainage treatment,and 2 patients developed fever,which was improved after symptomatic treatment.One patient died of respiratory failure six months after treatment.Conclusion Arterial embolization combined with local ablation can improve the symptoms of pain and prolong the survival time of patients with chest wall tumors.This combination therapy is less traumatic and clinically safe,and it can be used as an effective treatment for patients with recurrent and refractory chest wall tumors.

This study aims to establish a multiplex TaqMan fluorescence quantitative PCR(qPCR)assay for Pasteurella multocida(P.multocida).Specific primers and fluorescent labeling probes were designed based on the sequences of five podoplanar genes of P.multocida hyaC-hyaD,bcbD,dcbF,ecbJ,and fcbD in the NCBI database.We adjusted the annealing temperature by gradient setting,optimized the primer and probe concentrations by matrix method,constructed standard curves,and performed specificity,sensitivity and reproducibility tests,and finally established mul-tiplexed TaqMan qPCR assays for these five genes.The results showed that the established assay had a good linear relationship between the amplification curves.The sensitivity of this method was high,10-100 times higher than that of ordinary PCR;the specificity was strong,and there was no amplification curve in the DNA detection of eight pathogenic bacteria such as Bacillus,Proteus mirabilis,Staphylococcus aureus,and Rhizoctonia rad iodurans.This assay had a good linear rela-tionship,and the coefficients of variation for Ct values of the inter-and intra-group reproducibility tests were all less than 3％,and the detection rate of this assay was 11.25％higher than the con-ventional PCR assay through the detection of 90 clinical samples.The method established in this study is able to detect P.multocida rapidly and sensitively,which is important for its rapid clinical and laboratory diagnosis.

Objective:To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose ( 18F-FDG) positron emission computed tomography/computed tomography(PET/CT) in advanced non-small cell lung cancer(NSCLC) treated with first-line immune checkpoint inhibitor (ICI) combined with chemotherapy. Methods:A retrospective study was conducted to evaluate patients with advanced NSCLC who underwent baseline PET/CT before treatment at the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2021. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-offs for metabolic parameters of PET/CT, including total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUV max). Kaplan-Meier method, Log-rank test, and Cox regression model were used to calculate the overall survival (OS) and the progression-free survival(PFS). Results:A total of 44 patients were enrolled. Univariate analysis showed that the factors influencing PFS were TMTV and the number of metastatic sites ( χ2=4.19, 11.28, P<0.05) and the factors influencing OS were TMTV and TLG ( χ2=14.96, 6.05, P<0.05). Multivariate analysis suggested that number of metastatic sites was an independent prognostic marker for PFS ( P=0.011) and TMTV was an independent prognostic marker for OS ( P=0.038). Conclusions:TMTV is a prognostic indicator of OS while the number of metastatic sites is a prognostic indicator of PFS in advanced NSCLC patients who received first-line ICI combined with chemotherapy, but further prospective studies are needed.

Objective:To evaluate clinical efficacy of first-line immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) in patients with newly diagnosed non-small cell lung cancer (NSCLC) with brain metastasis (BM).Methods:Clinical data of patients with BM of NSCLC diagnosed in Henan Cancer Hospital from December 2017 to June 2021 were retrospectively analyzed. Patients were treated with programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitor combined with or without brain RT. The survival rate was calculated by Kaplan-Meier analysis. Univariate analysis was performed by log-rank test and multivariate analysis was performed by Cox model.Results:The median follow-up time was 13 months (range 4-49 months). The median overall survival (OS) time was 24 months, and the 1-, 2- and 3-year OS rates were 75.8%, 44.7%, and 33.6%, respectively. The 1-year intracerebral progression-free survival (iPFS) was 68.8%. The intracerebral objective response rate (icORR) of the RT-ICI group and ICI group was 71.4% and 52.6%, respectively, and the intracerebral disease control rate (icDCR) was 96.4% and 89.4%, respectively ( P=0.122,0.291). Univariate analysis showed that the 1-, 2- and 3-year OS rates of patients with high graded prognostic assessment (GPA) scores were 100%, 85.7% and 35.7%, respectively. The 1-, 2- and 3-year OS rates of patients with low GPA scores were 68.3%, 33.6% and 33.6%, respectively ( P=0.115). The 1-, 2- and 3-year OS rates of patients in the RT-ICI group were 88.7%, 58.7% and 44.0%, respectively, and 63.6%, 20.9% and 20.9% for their counterparts in the ICI group, respectively ( P=0.022). The 1-, 2- and 3-year OS rates of symptomatic patients with BM were 60.9%, 33.8% and 33.8%, respectively, while 84.6%, 53.1% and 39.8% for asymptomatic counterparts, respectively ( P=0.021). Multivariate analysis showed that no symptoms of BM and brain RT were the independent influencing factors of OS rate ( P=0.038, 0.037). Conclusions:First-line ICI combined with brain RT can improve the survival rate of patients with BM of NSCLC. It is recommended that patients with BM should receive RT as soon as possible, especially those with brain symptoms.

Objective:To investigate the safety and efficacy of C-arm CT laser-guided puncture combined with digital subtraction angiography (DSA)for percutaneous renal pelvic catheter drainage in the treatment of hydronephrosis caused by pelvic malignancy.Methods:A retrospective analysis was performed on the data of 56 patients with ureteral obstruction caused by pelvic malignancy admitted to the Affiliated Cancer Hospital of Zhengzhou University from February 2020 to August 2021, including 10 males and 46 females. The mean age of the patients was (54.0±10.1)years old. The causes were colorectal cancer (7 cases), bladder cancer (3 cases), cervical cancer (36 cases), endometrial cancer (3 cases), ovarian cancer (2 cases), pelvic metastasis of gastric cancer (4 cases) and pelvic sarcoma (1 case). There were 71 sides of renal pelvis dilation in 56 patients, with the degree of dilation ranging from 1.2cm to 5.0cm.The degree of hydronephrosis was mild on 36 sides, moderate on 27 sides, and severe on 8 sides. Preoperative blood urea nitrogen(9.90±6.22)mmol/L and creatinine (155.80±146.83)μmol/L.During the puncture and catheter drainage, the patient was placed in the prone position, the C-arm CT scan was used to plan the puncture path, and the laser positioning of the DSA flat panel detector was used to determine the skin puncture point. With local anesthesia, the puncture direction of the puncture needle was adjusted to make the skin puncture point, the tail of the puncture needle, and the laser fixation point present a state of "three-points in one-line" when the patient stopped breathing temporarily at the end of expiratory breath in a non-fluoroscopic state, so as to achieve the preset puncture angle. Subsequently, pyelocentesis was completed according to the planned puncture depth. After successful pyelocentesis, percutaneous external renal drainage tube insertion or ureteral stents were performed under DSA. The number of renal pelvis puncture, puncture time, radiation dose, deviation of external renal drainage tube insertion angle from puncture angle, as well as postoperative hemoglobin changes, renal function recovery and complications were recorded.Results:In this group, 56 cases of 71 sides of renal pelvis puncture and catheter drainage were successfully completed, and the success rate of the operation was 100.0% (71/71). The success rate of the first needle puncture was 97.2% (69/71). Those who failed the first needle puncture succeeded in the second puncture during the operation. The puncture time of renal pelvis was (1.9±1.8) min.The intraoperative radiation dose was (2.7±1.5) mSV. The external drainage tube of the renal pelvis was placed on 53 sides, and the external drainage tube was placed on 29 sides with the same angle as the preset angle, and 24 sides with a deviation within 3°.On the first day after operation, there was no significant difference in hemoglobin compared with that before operation, urea nitrogen (5.31±1.99) mmol/L and creatinine (62.25±16.72) μmol/L were re-examined after operation, and the differences were statistically significant compared with those before operation ( P=0.008, P=0.002). No serious surgery-related complications occurred in any patient. Conclusion:C-arm CT laser-guided puncture combined with DSA percutaneous renal pelvic catheter drainage could be safe and effective in the treatment of ureteral obstruction caused by pelvic malignancy.

Objective:To analyze the failure patterns and influencing factors of stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (ES-NSCLC).Methods:113 cases of ES-NSCLC treated with SABR from 2012 to 2020 in our hospital were retrospectively analyzed. The failure patterns, recurrence time, recurrence site and influencing factors were analyzed. Kaplan-Meier method was used to calculate the local recurrence rate, regional lymph node recurrence rate and distant metastasis rate. Univariate analysis was performed by Log-rank test, and multivariate analysis was performed by Cox model.Results:The median follow-up time was 58 months (range: 6-108 months), and a total of 45 patients (39.8%) recurred. The median recurrence time was 36 months. Distant metastasis (DM) occurred in 31 patients (27.4%) and DM alone in 24 patients (21.2%). Local recurrence (LR) was developed in 12 patients (10.6%) and LR alone in 7(6.2%). Regional lymph node recurrence (RR) occurred in 11 patients (9.7%) and RR alone in 6 patients (5.3%). LR combined with RR was observed in 1 case (0.9%), LR combined with DM in 3(2.7%), LR combined with RR and DM in 1(0.9%), and RR combined with DM in 3(2.7%). The 1-, 2-, 3-, 4-and 5-year recurrence rates were 5.4%, 16.6%, 27.5%, 44% and 51.2%, respectively. Univariate and multivariate analyses suggested that EGFR mutation was an influencing factor of high recurrence rate.Conclusion:ES-NSCLC patients treated with SABR alone have a high recurrence rate, and DM is the most common mode of failure. Follow-up consolidation therapy is recommended, especially for EGFR mutation-positive NSCLC patients.

Objective:To investigate the relationship between lung immune prognostic index (LIPI) and the prognosis of locally advanced non-small cell lung cancer (LA-NSCLC) treated with radiochemotherapy.Methods:A retrospective analysis was conducted for the clinical data of LA-NSCLC patients who received radiochemotherapy in the Affiliated Cancer Hospital of Zhengzhou University from 2013 to 2019. According to the hematologic test result of the derived neutrophil-to-lymphocyte ratio (dNLR) and the lactate dehydrogenase (LDH), the patients were divided into three groups according to their LIPI scores, namely the good-LIPI group with dNLR ≤ 3 and LDH ≤ upper limit of normal (ULN), moderate-LIPI group with dNLR >3 or LDH > ULN, and poor-LIPI group with dNLR >3 and LDH > ULN. Moreover, the overall survival (OS) and the progression-free survival (PFS) were calculated using the Kaplan-Meier method, the Log-rank test, and the Cox regression model.Results:A total of 238 patients were enrolled, and their median follow-up time was 37.1 months, median PFS 16.1 months, and median OS 30.6 months. The OS and PFS of the poor-LIPI group were significantly worse than those of the good- and moderate-LIPI groups ( χ2= 9.04, 2.88, P<0.05). The univariate analysis showed that the factors influencing OS included gender, pathological type, epidermal growth factor receptor (EGFR) mutations, and LIPI ( χ2=6.10, 13.66, 10.58, 9.04, P<0.05), and the PFS was only affected by the LIPI ( χ2=2.88, P = 0.03). Multivariate analysis suggested that EGFR mutations and LIPI were independent prognostic markers for OS ( HR = 1.31, 1.36; 95% CI: 1.03-1.67, 1.05-1.76; P<0.05). Conclusions:The LIPI is a potential prognostic indicator of radiochemotherapy in LA-NSCLC, and this result should be further confirmed by prospective studies.