The use of tyrosine kinase inhibitors （TKI） has been an important advance in the systemic treatment of hepatocellular carcinoma， but their sustained anti-angiogenic therapy leads to increased tumor hypoxia， accelerates the development of a hypoxic microenvironment and promotes the expressions of hypoxia-inducible factors （HIF）， thereby inducing drug resistance of tumor patients to TKI. This paper summarizes the mechanism of action of HIF mediating TKI resistance in hepatocellular carcinoma in aspects of metabolic reprogramming， abnormal expressions of cancer and cancer-associated genes， and ferroptosis， and sorts resistance response strategies to provide reference for clinical solutions to TKI resistance issues. As results show， HIF/ glycolysis axis inhibitors （isoflavonoid genistein， simvastatin， etc.） can improve TKI resistance based on metabolic reprogramming mechanism； oncogene-targeted inhibitors combined with TKI （the combination of capsaicin and sorafenib） can improve TKI resistance based on abnormal expression of cancer and cancer-related genes； fatty acid synthase inhibitor （orlistat） can improve TKI resistance based on ferroptosis mechanism.

Objective To explore the clinical characteristics of patients with drug-induced liver injury(DILI),so as to provide references for its diagnosis and treatment.Methods The clinical data of inpatients diagnosed as DILI in The Third Affiliated Hospital of Naval Medical University(Second Military Medical University),from Jan.2017 to Dec.2021 were retrospectively analyzed,including basic information,underlying diseases,drug use history,clinical manifestations,laboratory indexes,severity and prognosis of DILI.Results Among 145 patients with DILI,112 cases(77.24％)were hepatocellular type,25 cases(17.24％)were cholestatic type,and 8 cases(5.52％)were mixed type.The types of drugs causing DILI mainly included traditional Chinese medicine,proprietary Chinese medicine and anti-infective drugs,and the proportions were 48.72％(76/156),16.03％(25/156),and 10.26％(16/156),respectively.The common clinical manifestations of DILI patients were jaundice(76.55％),poor appetite(52.41％),and fatigue(49.66％).The levels of alanine transaminase(ALT),aspartate transaminase,alkaline phosphatase(ALP),total bilirubin(TBil),γ-glutamyl transferase and albumin(ALB),as well as the length of hospital stay and severity distribution were significantly different among different types of liver injury(all P＜0.05).The levels of ALT and ALB in the good prognosis group were significantly higher than those in the poor prognosis group,while the levels of TBil and international normalized ratio in the good prognosis group were significantly lower than those in the poor prognosis group(all P＜0.05).Multivariate analysis showed that INR was an independent predictor of the prognosis of DILI(P＜0.05).Conclusion Serum biochemistry indicators can help to identify the clinical classification and prognosis of DILI.Traditional Chinese medicine,proprietary Chinese medicine and other drugs can cause DILI.Medical staff should pay attention to it and strengthen public health education.

OBJECTIVE To establish methods to identify the chemical components of Gantaishu capsule， and determine the contents of 6 index components including glycyrrhizic acid. METHODS The chemical components of Gantaishu capsule were determined by HPLC-TOF/MS； the contents of 6 index components including glycyrrhizic acid were determined by UPLC-MS/MS. RESULTS A total of 41 chemical components were identified in Gantaishu capsules. The linear ranges of glycyrrhizic acid， mangiferin， luteolin， costunolide， oleanolic acid and berberine were 200-10 000 ng/mL（r were all greater than 0.999）. The limits of quantification were 200， 20， 10， 1， 10， 0.5 ng/mL， and the limits of detection were 100， 10， 5， 0.5， 5， 0.25 ng/mL， respectively； RSDs of precision， stability （24 h） and reproducibility tests were all less than 5.0% （n＝6 or n＝3）； the recoveries were 99.05%-101.08% （RSD were all less than 2.0%， n＝6）. The contents of them were 2.42-2.66， 0.85-1.16， 0.35-0.46， 6.18- 6.46， 0.99-1.29， 5.22-5.56 mg/g. CONCLUSIONS The established methods for identification and content determination are rapid and simple， and can be used for the identification of chemical components and the content determination of index components in Gantaishu capsule.

Melanoma is the most aggressive skin malignant tumor, which is prone to early metastasis and relapse after treatment. Therapeutic tumor vaccines are new immunotherapies, which have the advantages of low toxicity and inhibiting tumor metastasis. Melanoma has a high mutation load and a large number of specific antigens. Currently, various types of tumor vaccines have been developed for melanoma, especially those based on dendritic cells (DC). Although the efficacy of therapeutic DC vaccines in melanoma has been confirmed by a number of studies, these vaccines still have problems such as insufficient immune effect and poor efficacy when used alone, and there is still a large room for improvement. In this paper, the current research status of therapeutic DC vaccines for melanoma was reviewed, and the research key points and optimization strategy of therapeutic DC tumor were prospected.

Objective To provide the evidence for clinical medication safety by the investigation of the risk factors of linezolid-related thrombocytopenia in cancer patients in the department of hepatobiliary surgery. Methods Patients who received linezolid for anti-infective treatment from January 2017 to December 2021 were selected. The patients were divided into thrombocytopenia group and non-thrombocytopenia group according to whether thrombocytopenia occurred or not after administration of linezolid. The general data and laboratory indicators of the two groups were compared, and the risk factors of linezolid-related thrombocytopenia were screened by multivariate logistic regression analysis. Results A total of 104 patients were included in the study, including 84 patients who underwent surgery and 20 patients who did not. The incidence of linezolid-related thrombocytopenia was 24.0%. There were significant differences in gender, age, duration of linezolid use, platelet count, white blood cell count, alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin, creatinine, estimated glomerular filtration rate between the two groups (P<0.05); logistic regression analysis suggested that age ≥60 years (OR=7.093; P=0.017), duration of linezolid use ≥12 days (OR=4.399; P=0.035), baseline platelet count ≤200×10⁹/L (OR=8.470; P=0.004), baseline AST≥50 U/L (OR=15.465; P<0.001), and baseline white blood cell count ≥11×10⁹/L (OR=11.436; P=0.001) were the risk factors for linezolid-related thrombocytopenia in cancer patients. Conclusion During the treatment of linezolid in cancer patients, attention should be paid to the adverse reactions of thrombocytopenia in the patients, especially those with old age, long-term treatment, low baseline platelets, poor baseline liver function, and high baseline white blood cell counts.

OBJECTIVE To optimize the formulation of Rebamipide sustained -release tablets and investigate its stability . METHODS On the basis of single factor investigation ，the central composite design -response surface method was adopted to optimize and validate the formulation using the dosage of hypromellose K 100M（HPMC K 100M）and poloxamer 188 as factors ， comprehensive scores （Y）of the in vitro cumulative release （Y0.5，Y2，Y6，Y10，Y12）of sustained -release tablets at 0.5，2，6，10 and 12 h ，correlation coefficient of in vitro cumulative release curve （R）and viscosity （N）as evaluation indexes . The stability of the optimized prescription was validated . RESULTS The optimized formulation was as follows ：rebamipide 150.0 mg，L-arginine 75.0 mg，poloxamer 188 65.6 mg（13.12%），HPMC K 100M 114.5 mg（22.90%），microcrystalline cellulose proper amount ，micro- powder silica gel 5 mg（1%），and the total prescription amount was 500 mg. According to 3 validation experiments ，the contents of rebamipide in sustained -release tablets were 100.61%，98.69% and 99.01%，respectively. The obtained sustained -release tablets released for 12 h continuously ，with in vitro cumulative release ≥90%，with good repeatability . The deviation between the real values and the predicted values of the 3 indicators Y，N and R were all less than 10%. In the stability tests ，light would silightly reduce the content after 10 days of storage at 25 ℃andrelativehumidity （90±5）%，the tablets expanded and split from the 5th day，and the release rate slowed down ；in high temperature ，accelerated and long -term stability tests ，the properties of the tablets have no significant changes ，and the content and in vitro cumulative release have no significant differences compared with the 0th day or 0th month . CONCLUSIONS Successfully optimized the formlation of Rebamipide sustained -release tablets . The sustained - release tablets obtained have sustained -release effect and should be stored in a dark place under dry conditions .

Objective To explore the strategies of perioperative antithrombotic therapy in the patient undergoing revision total hip arthroplasty after coronary stent implantation. Methods The antithrombotic therapy in one patient undergoing revision total hip arthroplasty after coronary stent implantation was analyzed with the review of related literatures. Results The patient developed non-ST segment elevated myocardial infarction due to the stop of aspirin three days before operation and no low molecular weight heparin was used. The antithrombotic treatment and prevention of venous thromboembolism were analyzed. Conclusion Antithrombotic therapy should be selected reasonably in patients undergoing revision total hip arthroplasty after coronary stent implantation.

Objective To explore the effect and significance of electronic account books on the management of anesthesia and psychotropic drugs. Methods The data of electronic account books from January 2020 to June 2020 in the inpatient pharmacy of the hospital (observation group), and manual account books from July 2019 to December 2019 (control group) were collected respectively. The data of daily accounting time, monthly settlement accounting time and accounting accuracy between the two groups were compared and analyzed. Results The daily average time for pharmacists to manually accounting was (162.8±22.5) min, and the daily average time for pharmacists to make accounts electronically was (33.2±7.0) min. It took (245.5±7.2) min for manual accounting of monthly settlement and (46.8±2.5) min for electronic accounting of monthly settlement. The accuracy rate of daily counting records, special account books, special register and empty ampoule waste paste recovery records included in electronic accounting is up to 100%. Conclusion The implementation of electronic account books not only significantly improved the work efficiency of pharmacists, but also strengthened drug supervision, formed a comprehensive traceability system, which could ensure the safety of clinical medication, and make the management of narcotic psychotropic drugs more efficient and standardized.

OB JECTIVE To study the anti-inflammatory effect of couplet medicinals of Achyranthes bidentata -Eucommia ulmoides. METHODS Mouse macrophage RAW 264.7 were divided into blank group ，model group ，A. bidentata group（800 μg/mL），E. ulmoides group（800 μg/mL）and low- ，medium- and high- concentration groups of couplet medicinals of A. bidentata - E. ulmoides （400，800，1 600 μg/mL）. Excep for blank group and model group ，the other groups were added with corresponding drugs for 6 hours；then blank group was continued to add into the medium ，while model group was added into 10 μg/mL lipopolysaccharide （to induce the inflammatory model ）；other groups were added into corresponding drugs and 10 μ g/mL lipopolysaccharide. The levels of inflammatory factors [nitric oxide （NO），interleukin-1β（IL-1β），IL-6，tumor necrosis factor-α （TNF-α）] were detected ，and Jin ’s formula was used to evaluate the effects of A. bidentata -E. ulmoides . The expression of inducible nitric oxide synthase （iNOS），cyclooxygenase-2（COX-2），nuclear factor kappa-B （NF-κB）and inhibitor α of NF-κB （IκBα）as well as the phosphorylation of NF-κB p65，IκB kinase（IKK），p38 mitogen-activated protein kinase （p38 MAPK）， extracellular signal-regulated kinase （ERK）and c-Jun N-terminal kinase （JNK）were determined. RESULTS Compared with blank group，the level of inflammatory factors ，protein expression of iNOS and COX- 2 as well as the phosphorylation of NF-κB p65， IKK，p38 MAPK，ERK and JNK were increased significantly （P＜0.01），while the protein expression of IκBα was decreased significantly（P＜0.01）. After intervention of couplet medicinals of A. bidentata -E. ulmoides ，the level of inflammatory factors ，the expression or phosphorylation of above proteins were reversed significantly （P＜0.05 or P＜0.01），and couplet medicinals of A. bidentata-E. ulmoides had a synergistic effect. CONCLUSIONS The couplet medicinals of A. bidentata -E. ulmoides have synergistic anti-inflammatory effect on RAW 264.7 cells. Its mechanism may be related to the inhibition of NF-κB/MAPK signaling pathway related protein expression.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.