AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra -performance liquid chromatography-tandem mass spectrometry (UPLC / MS / MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg / kg sorafenib group, 0.5 mg / kg dapagliflozin group, 1 mg / kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg / kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/ MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the C

Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.

Liver fibrosis is a key step in the progression of chronic liver diseases to liver cirrhosis and even liver cancer. In recent years， a large number of studies have shown the necessity of intervening in the process of liver fibrosis， and various anti-liver fibrosis drugs and active ingredients have been discovered. Non-coding RNAs also play an important role in the process of liver fibrosis， and searching for upstream non-coding RNAs that can regulate signaling pathways can provide new insights for anti-liver fibrosis treatment. This article introduces the process of liver fibrosis mediated by the TGF-β， Wnt/β-catenin， PI3K/Akt/mTOR， NF-κβ， Hippo， and MAPK signaling pathways， lists the latest anti-liver fibrosis drugs or active components in each signaling pathway， and summarizes the research advances in anti-liver fibrosis targets and drugs mediated by related non-coding RNAs， so as to provide new research ideas and treatment methods for anti-liver fibrosis treatment.

Objective:To explore and analyze the selection of surgical methods for supratentorial intracerebral hemorrhage.Methods:A total of 260 patients with spontaneous intracerebral hemorrhage who underwent surgery in Department of Neurosurgery, Suzhou Hospital Affiliated to Nanjing Medical University from January 2017 to December 2021 were included in the study by retrospective case analysis. According to different surgical methods, they were divided into three groups: large bone flap group ( n=116), conventional bone flap group( n=89)and stereotactic group( n=55). The large bone flap group underwent standard supratentorial large bone flap craniotomy, the conventional bone flap group underwent conventional bone flap craniotomy, and the stereotactic group underwent stereotactic hematoma puncture suction + drainage. Clinical indicators such as operation time, intraoperative bleeding, pulmonary infection, length of hospital stay, and Glasgow outcome scale (GOS) at 6 months of postoperative follow-up, and the proportion of good prognosis (GOS 4-5) were calculated. Measurement data with normal distribution were expressed as mean±standard deviation( ± s), count data were expressed as cases and percentages (%). Results:In the large bone flap group, the operation time, intraoperative bleeding, hospital stay, pulmonary infection, postoperative rebleeding were(193±24) min, (625±65) mL, (46±11) d, 102 patients(87%), 9 patients(7.8%), and (124±17) min, (297±35) mL, (32±9) d, 29 patients(33%), 4 patients(4.4%)in the conventional bone flap group, and (73±11) min, (53±15) mL, (21±4) d, 10 patients(18%), 2 patients(3.6%)in stereotactic group. All patients were followed up for 6 months, and 165 patients (63.5%) had good prognosis (GOS 4-5), including 36 patients (31%) in the large bone flap group, 82 patients (93.2%) in the conventional bone flap group, and 47 patients (85.5%) in the stereotactic group.Conclusion:Standard large craniectomy has sufficient effect of decompression, and is suitable for serious life threatening hematoma; Conventional craniotomy has advantages in the treatment of secondary intracerebral hemorrhage. Stereotactic surgery has the characteristics of short operation time, less intraoperative bleeding, short hospital stay and low incidence of pulmonary infection, which is worthy of promotion in the treatment of primary intracerebral hemorrhage.

Drug-drug interactions (DDI) of tyrosine kinase inhibitors (TKIs) mediated by metabolic enzymes and transporters have become an important issue in clinical practice recently. In addition to CYP450 enzymes, uridine diphosphate glucuronidases (UGTs) are another class of metabolic enzymes involved in the metabolism of TKIs, and most TKIs can inhibit the UGTs in vitro. Potential clinically meaningful DDIs may occur with the co-administration of TKIs and substrates or inhibitors of UGTs. This paper will mainly focus on the UGTs-mediated drug-drug and the effect of UGT1A genotype on the drug interactions of TKIs and explores strategies to address, aiming to provide clinicians and pharmacists with references for the safe and rational application of TKIs.

Intracranial aneurysms will lead to subarachnoid hemorrhage, which has a high mortality and morbidity risk. Screening high-risk aneurysms for preventive intervention has a positive effect, considering the widespread presence of unruptured aneurysms in the general population, this article reviews the risk factors of aneurysm rupture from the aspects of epidemiology, pathology, morphology and hemodynamics. In terms of epidemiology, smoking history, hypertension, age, gender and family inheritance are all closely related to the risk of aneurysm rupture. In terms of pathology, inflammation on the wall of intracranial aneurysm may be related to the risk of aneurysm rupture. In imaging, the size of intracranial aneurysms, location, the characteristics of the artery wall and some morphological and hemodynamic parameters can be used as evaluation index of fracture risk factors, at the same time the growth of intracranial aneurysm is one of the high risk indicators, the indicators for us in the future to establish intracranial unruptured aneurysms rupture risk factors evaluation model is of great significance.

Objective To clarify the relationship between intracranial pressure monitoring and prognosis of patients with traumatic brain injury after decompressive craniectomy.Methods From December 2015 to December 2017,48 head-injured patients in Affiliated Suzhou Hospital of Nanjing Medical University were enrolled,who were underwent decompressive craniectomy in this retrospective study.The patients were subdivided into 2 groups based on whether postoperative was monitored (n =19) or not (n =29).The prognosis was evaluated by Glasgow Outcome Scale score,with 1 point of prognosis death,2 to 3 points of poor prognosis,and 4 to 5 points of good prognosis.Count data were expressed as a percentage (％).Count data were expressed as percentage (％).The chi-square test was used to compare the difference in the rate of good prognosis and mortality between the two groups.Results The mortality of monitoring group (10.5％) was significantly lower than that of control group (37.9％) (x2 =4.365 5,P =0.036 7) during hospitalization,The rate of good prognosis in the monitoring group (68.4％) and the control group (44.8％) was not statistically significant (x2 =2.573 8,P =0.108 6).Condusion The study showed that continuous monitoring in patients with severe craniocerebral injury could reduce the mortality of patients during hospitalization,but had no significant effect on the improvement of prognosis.

Objective To observe late effect of 60Co radiation accident on eye lens in the victims.Methods Medical observations of eye lens were performed on ten victims accidentally exposed to 60Co sources in four radiation accidents that have occurred from 1986 to 2000 in Henan Province.Pathological changes of the eye lenses were examined by using slit lamp microscopy after mydriasis with compound tropicamide.Results Of these ten victims, Liang in a radiation accident in Kaifeng (in 1986), Mei in Xinxiang (in 1999) and Xu in Xuchang (in 2000) all had typical radiation-induced cataract 2, 3 and 6 years after irradiation, respectively.Follow-up observation of the lens showed the punctate and/or granular opacities present in the eye posterior subcapsular of Yan in Kaifeng accident, Jie in Zhengzhou (1987), and Tian, Yong and Yi in Xinxiang accident, featuring the early changes of radiation-induced cataract, but the posterior subcapsular opacities were not observed in Wang and Min in Xinxiang accident.Conclusions Focus should be on the eye lens as the target organ of radiation exposure in long-term follow-up of victims accidentally exposed to radiation source.Severity of the lens opacity induced by ionizing radiation is closely associated with radiation doses.

Objective To evaluate the long-term efficacy of recombinant human endostatin (rh-Endo) combined with FOLFOX4 as an adjuvant treatment for patients of stage Ⅱ and Ⅲ colorectal cancer.Methods Eligible patients were randomly assigned to receive FOLFOX4 or FOLFOX4 plus rh-Endo regimen in which patients receiving 7.5 mg/m2 Ⅳ on day 1-7,repeated every 2 weeks,to a total of 12 cycles in 6 months.Results A total of 197 eligible patients were accrued in this research with 105 patients in the control group and 92 patients in the experimental arm.Median follow-up period was 42 months.The baseline characteristics distributed were balanced by treatment.Rh-Endo combined with FOLFOX4 regimen resulted in significant improvement on DFS compared to FOLFOX4 regimen for patients with stage Ⅲ colon cancer (HR =0.19,95％ CI0.05-0.75,P =0.0124),and with a 34％ improvement on 3-year DFS and 81％ reduced recurrence.Although rh-Endo combined with FOLFOX4 regimen failed to make significant difference on DFS in the whole (HR =0.75,95％ CI 0.31-1.83,P =0.5589),it was also observed a 17％ improveiment on 3-year DFS.No statistical significant difference on DFS was observed in patients with stage Ⅱ disease.Conclusions Rh-Endo combined with FOLFOX4 regimen significantly improved the disease-free survival for patients with stage Ⅲ colorectal cancer,indicating that patients with stage Ⅲ disease,but not stage Ⅱ disease,can benefit from FOLFOX4 plus rh-Endo regimen in adjuvant treatment.

Objective To explore the long-term health effects of overexpose to radiation.Methods The 32 -41-year medical followed-up observations were performed for 25 persons exposed to ionizing radiation in the dose range of 0.10 -0.33 Gy. Observations were made of clinical symptom,eye lens,cytogenetics,immune function and endocrine function for these persons. Results The incidence of neurasthenic symptom was higher in exposed group than that in control group.2 cases suffered from liver cancer and esophageal cancer,respectively. Posterior capsule punctate phacoscotasmus of the lens wereobserved in 7 cases.There was I case of cataract in the exposed group. The frequencies of chromosomeaberration and micronucleis in peripheral blood lymphocyte in the exposed group were significantly higherthan those in control group (x2 =8.88,8.71,40.60,45.63,P ＜ 0.05 ).The average value of serum IgG was higher(t =2.16,P ＜0.05 ),while that of IgM was obviously lower in the exposed group (t =2.03,P ＜0.05).The average values of serum triiodothyronine (T3),thyroxine (T4 ) and thyroid-stimulating hormone (TSH) in the exposed group were obviously lower than those in the control group (t =2.40,3.54,2.13,P ＜0.05 ).Conclusions Overexposure has effect on lens,immune function,cytogenetics to some degree.It is important to observe the long-term health effect on overexposed persons.