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    Volume 25 Issue 8
    26 August 2020
    Effects of knocking down long intergenic non-coding RNA 00467 on the prognosis of patients with lung adenocarcinoma and its mechanism
    WANG Xianghai, XING Min, LYU Tangfeng, LIU Hongbing, SONG Yong
    2020, 25(8):  841-849.  doi:10.12092/j.issn.1009-2501.2020.08.001
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    AIM: To explore the effect of knocking down long intergenic non-coding RNA 00467 on the prognosis of patients with lung adenocarcinoma and its mechanism.  METHODS: Quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression level of linc00467 in the plasma of LAD patients and healthy volunteers. The overall survival (OS) was analyzed by Kaplan-Meier survival analysis and log-rank tests. Cell proliferation assays and Xenograft mouse model were used to confirm the effect of linc00467 expression on tumorigenesis in vitro and in vivo.RESULTS: linc00467 expression was up-regulated in the plasma of LAD patients compared with healthy volunteers. In addition, high levels of linc00467 expression were correlated with larger tumour sizes, lymph node metastasis and advanced TNM stages. High levels of linc00467 indicated a poor prognosis in LAD patients, multivariate analyses indicated that linc00467 expression could serve as an independent prognostic factor for overall survival of LAD. Functional experiments showed that knockdown of linc00467 could inhibit LAD cell proliferation in vitro and in vivo. CONCLUSION: linc00467 is involved in the progression of LAD and that linc00467 may be a novel diagnosis biomarker and a potential therapeutic target for LAD.

    Esveratrol inhibits NLRP3 inflammasome activation in rabbits with spinal cord injury
    JIANG Weiyu, HU Xudong, CHEN Yunlin, RUAN Chaoyue, XU Nanjian, WANG Yang, XU Dingli, ZHANG Jiaming, LI Haojie, MA Weihu
    2020, 25(8):  850-856.  doi:10.12092/j.issn.1009-2501.2020.08.002
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    AIM: To study the mechanism of resveratrol inhibiting NLRP3 inflammasome activation in rabbits with spinal cord injury.  METHODS: Fifty male Japanese big ear rabbits were randomly divided into 5 groups: blank control group (CON group), spinal cord injury model group (SCI group), low-dose resveratrol group (RSV(L) group), and resveratrol high-dose group (RSV(H) group), methylprednisolone group (MP group), 10 rabbits in each group. Spinal cord injury models were prepared in all four groups except the CON group. All groups received iv administration daily, and the same amount of normal saline was given to the CON group and the SCI group for 14 consecutive days. The Tarlov method was used to evaluate the neurobehavioral score in rabbits. The chromogenic substrate method was used to determine the MDA content and the activity of SOD and GSH-Px in spinal cord tissues. Western blot was used to determine the proteins expression of NLRP3, Caspase1 p20, IL-1β, Sirt1, NF-κB p65 in spinal cord neural tissues, HE staining to observe the pathological changes of spinal cord tissue. RESULTS: Resveratrol increased the behavioral score of spinal cord injury rabbits, promoted the repair of injured tissues, reduced the MDA content, increased the activity of SOD and GSH-Px in spinal cord tissues, down-regulated the expression of NF-κB p65, up-regulated the expression of Sirt1 in spinal cord tissues, and inhibited expression of NLRP3 in inflammasome (reduction in expression of NLRP3, Caspase1 p20, and IL-1β in spinal cord tissues). CONCLUSION: Resveratrol can promote the recovery of spinal cord injury rabbits, and its mechanism may play a role by activating Sirt1, regulating NF-κB pathway and antioxidant level in vivo, and further inhibiting the activation of NLRP3 inflammasome.
    Effects of dexmedetomidine on renal function and serum inflammatory factors in sepsis rats
    YANG Huifang, LUO Ying, ZHAO Li
    2020, 25(8):  857-861.  doi:10.12092/j.issn.1009-2501.2020.08.003
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    AIM: To investigate the effects of dexmedetomidine (Dex) on renal function and serum inflammatory factors in sepsis rats.  METHODS: Sixty male SD rats were divided into three groups: blank group, model group and DEX group (n=20). The blank group did not take any measures. The model group and DEX group were injected with lipopolysaccharide intravenously to construct sepsis rat model. Then the Dex group was injected with dextromethomidine injection for 7 μg·kg-1·h-1, and the dose was reduced to 5 μg·kg-1·h-1 after 15 minutes. The model group was continuously pumped for 30 minutes with equal volume of normal saline. At 12 h, 24 h and 48 h after operation, six rats in each group were taken from the abdominal vein blood. The serum creatine (Scr) and blood urea nitrogen (BUN) levels were measured by colorimetry, and the serum tumor necrosis factor-α (TNF-α) was measured by ELISA. The levels of TNF-α, IL-6 and IL-1β were measured. The rats were killed and the right kidney was taken, the pathological changes of renal tissue were observed by HE staining. RESULTS: At 12 h, 24 h and 48 h after operation, the levels of Scr and BUN in the model group and Dex group were higher than those in the blank group (P<0.05), while those in Dex group were lower than those in the model group (P<0.05). At 12 h, 24 h and 48 h after operation, there was no significant difference in the levels of Scr and BUN in the blank group (P>0.05), and the levels of Scr and BUN in the model group and Dex group increased in turn (P<0.05). The levels of TNF-α, IL-6 and IL-1β in the model group and Dex group were higher than those in the blank group (P<0.05) and lower than those in Dex group (P<0.05) at 12 h, 24 h and 48 h postoperatively. There was no significant difference in the levels of TNF-α, IL-6 and IL-1β in the blank group (P>0.05). The levels of TNF-α, IL-6 and IL-1β in the model group and DEX group increased in turn (P<0.05). At 12 h, 24 h and 48 h after operation, HE staining showed that there was no abnormal change of renal tissue in the blank group, and pathological changes were seen in the model group and DEX group, and gradually increased with the increase of time. Pathological changes in DEX group at all-time points were less than those in the model group. CONCLUSION: Dexmedetomidine can protect renal function and inhibit the expression of serum inflammatory factors in sepsis rats.
    Experimental study on the effect of curcumin on endometriosis in rats
    SHEN Longde, LI Ailu, LI Lichun, WU Yinyin, SHEN Longyuan, JIANG Qiuxia, HE Jinxi, WU Zhifen, YU Liji, ZHANG Xiaohong
    2020, 25(8):  862-868.  doi:10.12092/j.issn.1009-2501.2020.08.004
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    AIM: To analyze the effect of curcumin on the expression of transcription factors Twist1, Twist2, E-cadherin and Syndecan-1 in rats with endometriosis.  METHODS: Thirty SD rats were randomly divided into five groups: model group, low dose curcumin group (25 mg·kg-1·d-1), medium dose curcumin group (50 mg·kg-1·d-1), high dose curcumin group (100 mg·kg-1·d-1) and gestrinone group (0.5 mg·kg-1·d-1). There were 6 rats in each group, and 5 rats in sham operation group were set up as blank control group. The expression of Twist1, Twist2, E-cadherin and Syndecan-1 was detected by immunohistochemistry. RESULTS: Compared with the model group, the ectopic tissue volume of curcumin group and gestrinone group was significantly lower, the difference was statistically significant (P<0.05). Positive Twist1 was mainly located in the nucleus, positive Twist2 was mainly located in the cytoplasm, positive E-cadherin and Syndecan-1 staining was mainly located in the epithelial cell membrane, rarely in individual cytoplasm. Compared with the model group, the scores of Twist1, Twist2 and Syndecan-1 in each dose group of curcumin and gestrinone group were significantly lower, and the scores of Twist1, Twist2 and Syndecan-1 in low and middle dose curcumin group were significantly higher than those in gestrinone group, and the scores of E-cadherin were lower than those in gestrinone group (P<0.05). The scores of Twist1, Twist2, E-cadherin and Syndecan-1 in high dose curcumin group were significantly higher. There was no significant difference between the high dose curcumin group and gestrinone group (P>0.05). CONCLUSION: Curcumin can reduce the expression of Twist1, Twist2 and Syndecan-1, increase the expression of E-cadherin, and inhibit the growth of endometrium in the model rats, so as to achieve the purpose of treatment.
    Drug clinical trial of COVID-19 in China: A brief analysis
    MU Xin, ZHAO Ying, ZHANG Lan, CUI Yimin, ZHANG Yongxiang, DU Guanhua
    2020, 25(8):  869-877.  doi:10.12092/j.issn.1009-2501.2020.08.005
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    AIM: To provide suggestion for research and development of drugs against coronavirus disease 2019 (COVID-19) by analyzing the characteristics of the drug clinical trial registration information of COVID-19 in China. METHODS: The clinical trials of COVID-19 were searched from Chinese Clinical Trial Registry, and the type, purpose, and design of the studies were analyzed. RESULTS: Totally 271 drug clinical trials have been registered till July 1st, 2020. Most of the drugs are marketed ones, including chemical drugs, traditional Chinese medicines, and biologics. Combined applications were adopted in some projects. Randomized or non-randomized parallel control trials were conducted in most projects. Others included single arm, sequential, and factorial design. CONCLUSION: To deal with the epidemic, it is important to conduct emergent drug clinical trials to find out effective drugs as soon as possible. However, some weaknesses and deficiencies on trials design, conduct and supervision were exposed in the drug clinical trials against COVID-19. It is suggested to enhance the scientific evaluation of candidate drugs, standardize the investigator initiated trials, and establish the national multi-subject research and development platform, and the collaborative and innovative key-task tackling mechanism, thus to improve the ability and level of antiviral drug research and development.
    Comparison of policies and guidelines regarding using of real world data/real word evidence
    WANG Minhui, ZHAO Yang, DENG Yazhong, XUE Fubo, XIE Haitang, YAO Chen
    2020, 25(8):  878-889.  doi:10.12092/j.issn.1009-2501.2020.08.006
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    China and foreign regulators have conducted multiple discussions on how to use Real World Data (RWD) and Real World Evidence (RWE), also published relevant guidelines and framework files. The development and promotion of RWD/RWE application in China is relatively late, and there is a gap of systems and conditions between China and developed countries. This article aims to learn from advantage experiences of other countries and provide some referential ideas for exploring a strategy of RWD/RWE applications suitable for China by analyzing and comparing the current RWD/RWE application-related policies and guidelines in different regions.
    Brief analysis on the measures for the management of instruments and equipment in phase Ⅰ drug clinical trials
    ZHANG Yanping, PEI Tong, HU Chaoying, ZHANG Lan
    2020, 25(8):  890-894.  doi:10.12092/j.issn.1009-2501.2020.08.007
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    AIM: To discuss the standardized management methods of drug clinical trial instruments and equipment based on the analysis of current situation of the management in drug clinical trial instruments and equipment in institutions.  METHODS: Through literature searching and our experience, we analyzed the nowadays problems in management of instruments and equipment, established and improved the management system, refined the standard operating procedures, promoted information management, and strengthened the construction of professional team of instrument and equipment management or database. RESULTS: The implementation of dedicated management ensured the whole implementation management, reduced the frequency in management problems, and improved the professional level of instrument and equipment management. CONCLUSION: The construction of standardized instrument and equipment management system is the premise of standardized development of drug clinical trials, which improves the management level of drug clinical trial instruments and equipment, ensures the authenticity and accuracy of trial data, and effectively enhances the quality of following drug clinical trials.
    Tocilizumab related adverse events: A cross-section analysis of FDA Adverse Event Reporting System
    ZHU Zhengyi, NI Yinghua, GAO Peng, WANG Huijuan, HUANG Lingfei, HU Yan, ZHANG Liwen, YANG Jufei, FANG Luo
    2020, 25(8):  895-902.  doi:10.12092/j.issn.1009-2501.2020.08.008
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    AIM: To analyze the adverse events (AE) of tocilizumab by using the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports related to tocilizumab were extracted from the FAERS database. Disproportionality analysis of reporting odds ratio (ROR) and Medicines and Healthcare Products Regulatory Agency (MHRA) methods were performed for safety signal detection. RESULTS: A total of 19 773 reports associated with tocilizumab as the primary or secondary suspected drugs were extracted from the FAERS database between July 2014 to March 2019. AEs of drug ineffective, pain, drug intolerance, fatigue and rash were commonly reported. There were 13 642 serious AE reports, and 602 reports of death outcome. The proportion of serious and death outcome AEs of male patients was significantly higher than female, and these proportions were significantly higher in children and elderly compared with others. Respectively 602 and 490 of tocilizumab signals were detected by ROR method and MHRA method, including common AEs such as infection, drug hypersensitivity, leukopenia, and hepatic enzyme increased, and signals not indicated in label, for instance, pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, were also detected. CONCLUSION: The commonly reported AEs of tocilizumab include drug inefficiency, pain, drug intolerance, fatigue and rash. Pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, which not indicated in label, should be further assessed and be cautious in COVID-19 treatment.
    Pharmacokinetics and pharmacodynamics of (S)-pantoprazole sodium enteric-coated tablets in healthy subjects
    XIANG Rongfeng, SUN Fengjun, XIONG Lirong, YU Mingjie, DAI Qing, CHEN Yongchuan
    2020, 25(8):  903-909.  doi:10.12092/j.issn.1009-2501.2020.08.009
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    AIM: To evaluate the pharmacokinetics and pharmacodynamics of (S)-pantoprazole sodium enteric-coated tablets in healthy subjects by using pantoprazole sodium enteric-coated tablets as a control drug.  METHODS: Thirty healthy Chinese subjects were enrolled in a randomized, open and positive control trial. The subjects were given 20 and 40 mg (S)-pantoprazole sodium enteric-coated tablets and 40 mg pantoprazole sodium enteric-coated tablets, respectively. The concentration of (S)-pantoprazole in the human plasma was determined by LC-MS/MS and the pharmacokinetic parameters were calculated by WinNonlin 6.4 software. The intragastric pH was monitored for 24 hours. The dose-effect relationship of drugs was evaluated. RESULTS: The main pharmacokinetic parameters of (S)-pantoprazole after single administration of 20 and 40 mg (S)-pantoprazole sodium and 40 mg pantoprazole sodium enteric-coated tablets were as follows: The Cmax were (1 635±410), (2 756±1 024) and (1 536±615) ng/mL, the t1/2 were (1.41±0.31), (1.55±0.64) and (1.35±0.22) h, the AUC0-t  were (3 623±1 322), (7 383±3 785) and (3 276±1 302) h·ng·mL-1; The main pharmacokinetic parameters of multiple administration were as follows: The Cmax were (1 704±239), (3 297±743) and (1 832±557) ng/mL, the t1/2 were (1.41±0.40), (1.58±0.64) and (1.45±0.22) h, the AUC0-t  were (3 587±1 040), (8 189±3 399) and (3 878±1 272) h·ng·mL-1. After the treatment, the time of pH>4.0 as a percentage of total time (%) after single administration were (32.98±10.7)%, (45.37±9.61)% and (32.63±14.63)%; and the time of pH>4.0 as a percentage of total time (%) after multiple administration were (45.12±11.97)%, (50.76±10.63)% and (41.67±7.1)%. CONCLUSION: Healthy subjects have linear kinetic characteristics of (S)-pantoprazole after single and multiple administrations, and the 40 mg (S)-pantoprazole sodium group has better efficacy than other dose groups. Healthy subjects were well tolerated.
    Bioequivalence of fluconazole capsules in healthy Chinese subjects
    LI Zhihui, LIU Jingyan, QIU Wen, CHEN Hong
    2020, 25(8):  910-915.  doi:10.12092/j.issn.1009-2501.2020.08.010
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    AIM: To compare the bioequivalence of two brands of fluconazole capsules (50 mg) made in Chengdu Brilliant Pharmaceutical Co., Ltd and Pfizer Pharmaceuticals Ltd. (held in France) in healthy volunteers under fasted and fed conditions. METHODS: The study was an open-label, randomized, two way-crossover study involving 52 healthy Chinese volunteers. A single oral test and reference fluconazole capsules (50 mg) were given to the volunteers under fasted and fed conditions. The plasma concentration of fluconazole was determined by LC-MS/MS method. The non-compartment model pharmacokinetic parameter calculation method was applied to calculate pharmacokinetic parameters and perform statistical analysis.RESULTS: The main pharmacokinetic parameters after oral administration of test and reference fluconazole capsules under fasted conditions were as follows, Cmax (1.32±0.21) μg/mL and (1.15±0.20) μg/mL; AUC0-t (52.84±7.91) μg·h·mL-1 and (51.49±8.15) μg·h·mL-1;AUC0-∞ (58.07±9.30) μg·h·mL-1 and (56.99±10.13) μg·h·mL-1, respectively. The main pharmacokinetic parameters after oral administration of test and reference fluconazole capsules under fed conditions were as follows, Cmax (1.04±0.14) μg/mL and (1.04±0.15) μg/mL;AUC0-t (50.64±7.08) μg·h·mL-1 and (49.91±9.13) μg·h·mL-1;AUC0-∞(56.79±9.26) μg·h·mL-1 and (56.06±11.58) μg·h·mL-1, respectively. The 90% confidential intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ under fasted and fed conditions were all between 80% and 125%. CONCLUSION: The two brands of fluconazole capsules were bioequivalent under fasted and fed conditions.
    Potential inappropriate medications use in the geriatric condition of frailty based on STOPPFrail criteria: A cross-sectional study 
    JIA Boying, ZHOU Shuang, ZHOU Ying, CUI Yimin
    2020, 25(8):  916-925.  doi:10.12092/j.issn.1009-2501.2020.08.011
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    AIM: To measure medication consumption and the prevalence of potentially inappropriate medications (PIMs) during hospitalization and hospital discharge in the geriatric condition of frailty and to provide bases for rational medications use and further deprescribing. METHODS: A clinical data questionnaire, including the basic situation of patients and medications was designed. Charlesson comorbidity index was used to determine the patient's burden and status and the number of medication consumption in the geriatric condition of frailty. The medication consumption was determined by examining Hospital Medication Administration Records. PIMs were defined using STOPPFrail deprescribing criteria and McLeod criteria, whose sensitivity was compared to determine the PIMs independent related factors. RESULTS: This study included 169 patients. The mean age of participants was 83.49±6.73, 42.6% were female. The median number of days spent in hospital was 19 (interquartile range (IQR)12-33). During the first 24 hours of hospitalization, the mean number of individual medications consumed was 9.01 (standard deviation 4.12). Of hospital discharge, the mean number of individual medications consumed was 11.27 (standard deviation 4.57). Over 60% of patients were prescribed at least one PIM at discharge and 7.69% had ≥3 PIMs. Leukotriene antagonists, proton pump inhibitors (PPIs), lipid-lowering medications and diabetic oral agents accounted for major PIMs. Compared with McLeod's criteria, STOPPfrail criteria was a more sensitive tool for 24-hour hospitalization and hospital discharge PIMs screening (t=6.78, P=0.00<0.01; t=10.10, P=0.00<0.01). Full implementation of STOPPFrail recommendations would have resulted in one-in-seven long-term medications being discontinued. CONCLUSION: High levels of medication consumption in the geriatric condition of frailty will result in high burden experienced by patients in the condition of frailty and continued prescribing of futile medications. It is necessary to improve and pay more attention to the safety of medications. The STOPPFrail criteria is highly sensitive, simple and easy to use. Screening for medication consumption in geriatric condition of frailty with STOPPFrail tool will decrease medication burden.
    Efficacy and safety of XELOX therapy in comparison with capecitabine monotherapy in adjuvant chemotherapy for elderly patients with colorectal cancer
    ZHANG Dezhi, LIU Meng, ZHU Shaogong, LIU Guiju, JI Jie
    2020, 25(8):  926-936.  doi:10.12092/j.issn.1009-2501.2020.08.012
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    AIM: To investigate the efficacy and safety of the XELOX therapy (capecitabine plus oxaliplatin) versus capecitabine monotherapy in adjuvant chemotherapy for elderly patients with colorectal cancer.  METHODS: This study included 195 elderly patients with early colorectal cancer (60-82 years old) who underwent R0 surgical resection from January 2010 to December 2017 in Zhengzhou People's Hospital. Patients received either adjuvant chemotherapy with capecitabine monotherapy or XELOX therapy after surgery (selective adjuvant chemotherapy based on patient ECOG score, physical status, physician assessment, patient tolerance, and willingness). The baseline clinical data were collected through the hospital case system and patients were followed up according to the trial protocol. Disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis. Cox risk ratio model was established to evaluate the efficacy of different adjuvant chemotherapy regimens with the same risk factors. Adverse reactions above level 2 (according to CTCAE 4.0) were recorded for safety analysis. RESULTS:The median follow-up of the study was 5.75 years (the follow-up time range: 0.30-7.50 years). The efficacy was evaluated in 195 patients enrolled in the study. The median disease-free survival (mDFS) was 5.0 years in the overall patient population, and the mDFS in the XELOX group was 5.5 years, significantly higher than the mDFS of the capecitabine monotherapy group for 3.6 years (P=0.047, 95%CI: 2.06-5.14). The overall median overall survival (mOS) was 7.1 years, and the mOS of the XELOX group was 7.1 years, significantly higher than the median total of the capecitabine monotherapy group mOS 4.5 years (P=0.021, 95% CI: 3.30-5.70). With the same risk factors, when the patients were younger than 70 years old, both the DFS (HR=0.74, P=0.036) and OS (HR=0.78, P=0.041) patients could benefit from the XELOX regimen; when the patients ≥70 years old, only DFS (HR=0.77, P=0.035) could benefit from the XELOX therapy. Regardless of the patient's comorbidities, the patient's DFS and OS benefit from the XELOX therapy. However, patient's DFS and OS can benefit from XELOX only when the number of lymph nodes examined was less than 12 nodes and the number of cycles of patients receiving adjuvant chemotherapy was ≥6 cycles. In terms of adverse reactions, the incidence of neutropenia (61.54% vs. 39.74%, P=0.003) and neurotoxicity (65.81% vs. 0%) were significantly higher in the XELOX therapy than the capecitabine monotherapy regimen. Other adverse reactions such as diarrhea, stomatitis, thrombocytopenia, hand-foot syndrome, anemia, nausea and vomiting, increased AST/ALT, and hair loss were not significantly different between the two groups (P>0.05). CONCLUSION: The XELOX therapy does not significantly increase adverse events in elderly patients, and elderly patients (age<70 years old) who combine oxaliplatin on the basis of capecitabine can significantly benefit from DFS and OS,but when the patients were≥70 years old, only DFS can benefit, while OS cannot.
    Effects of aripiprazole combined with duloxetine on the treatment effect and VEGF level in patients with refractory depression
    YANG Shitao, ZHU Yihong, TANG Wenxin
    2020, 25(8):  937-942.  doi:10.12092/j.issn.1009-2501.2020.08.013
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    AIM: To explore the effects of aripiprazole and duloxetine on refractory depression and the change of VEGF concentration during treatment.  METHODS: Ninety patients with refractory depression who were treated at the Fourth People's Hospital of Jiande from February 2017 to February 2019 were selected, and 40 healthy volunteers were recruited as healthy control groups. Random numbers table was used to divide patients into aripiprazole combined with duloxetine treatment group (combined treatment group) and duloxetine treatment group (monotherapy group). After 4 weeks of treatment, the differences in efficacy and adverse reactions between the two groups were evaluated. The difference of VEGF level between each group was compared. RESULTS: The effective rate was 88.8% in the combined treatment group and 80.0% in the monotherapy group. The effective rate between the two groups was not statistically significant (P<0.05). After 4 weeks of treatment, the HAMD score in the combined treatment group was lower than that in the monotherapy group, the difference was statistically significant (P<0.05). The difference in adverse reactions between the two groups was not statistically significant (R=0.641, P=0.624). The level of VEGF before treatment in the two treatment groups was higher than that in the healthy control group, and the difference was statistically significant (P<0.01). After treatment, the VEGF level of the two groups decreased compared with before treatment, and the difference was statistically significant (P<0.01). The level of VEGF in the combined treatment group was lower than that in the monotherapy group, and the difference was statistically significant (P<0.05). Pearson correlation analysis showed that the level of VEGF before treatment was positively correlated with the HAMD score (R=0.403, P<0.01), and VEGF decline level is positively correlated with HAMD score reduction rate (R=0.330, P<0.01). CONCLUSION: Aripiprazole combined with duloxetine has a better effect on refractory depression than duloxetine alone, and can significantly reduce the level of VEGF in peripheral blood.
    Targeting DNA damage response in tumor therapy
    ZHAO Wenchao, QIU Yanfang, TAN Rong
    2020, 25(8):  943-952.  doi:10.12092/j.issn.1009-2501.2020.08.014
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    Chemotherapy plays an important role in cancer treatment. With deeply understanding the mechanism of tumorigenesis, different chemotherapeutic drugs have been emerged as initial choices for cancer treatment. However, most patients gradually develop to chemotherapeutic resistance, resulting in failure to initial standard therapy. The mechanisms of chemoresistance are extensively explored. Recent studies indicated intrinsic or acquired alteration of DNA damage repair ability is the key determinant of chemoresistance. In this review, we present deregulation of DNA damage repair pathway in cancers and its involvement contributing to chemoresistance. Furthermore, we discuss strategies to sensitize chemotherapy by targeting at a parallel DNA repair pathway, which become promising approaches to overcome chemotherapeutic resistance.
    Exploration and expectation on treatment strategies of central nervous system diseases based on transporters at blood-brain barrier
    ZHONG Kailong, WANG Yongsheng, CHEN Fang, YE Yanrong
    2020, 25(8):  953-960.  doi:10.12092/j.issn.1009-2501.2020.08.015
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    The structural and functional integrity of the blood-brain barrier (BBB) is a prerequisite for the maintenance of the brain homeostasis and function. Because of the structural peculiarities of the BBB, macromolecules and hydrophilic substances can pass through it only by some BBB transporter-mediated mechanisms. At the same time, the BBB is also responsible for deportation of some endogenous or exogenous substances from the brain through the efflux transporters. The current research advances on some important transporters at the BBB closely related to central nervous system (CNS) drugs, have been summarized in this review. These transporters include ABC transporters, glucose transporters, transferring receptor, insulin receptor and so on. This review offers a overview of structures, functions, distributions, relationships with CNS disease and drugs and the factors influencing their expression of some transporters at the BBB. Clarifying these elements could make a big difference to promote the CNS drugs to reach the brain across the BBB. Moreover, it provides new insights for exploring pathogenic mechanisms of some CNS diseases and their treatment.