Leptomeningeal metastasis(LM)is a serious late complication in patients with solid tumors,which is common in patients with lung cancer,breast cancer and melanoma.In recent years,due to the progress of diagnosis,the diagnosis rate of LM has gradually increased.The main goal of the therapy is to maintain neurological function,improve the quality of life and the overall survival rate,and prolong the progression-free survival time of patients.Intrathecal therapy is one of the main treatments for LM,which can deliver drugs directly to the subarachnoid space.The traditional intrathecal drugs are methotrexate,cytarabine and thiotepa.With the development of new research,a variety of chemotherapeutic drugs,targeted drugs and immune checkpoint inhibitors have also been used in intrathecal therapy.In addition,different ways of intrathecal administration also bring new hope to patients.This article reviewed the clinical research progress of intrathecal therapy in the treatment of LM.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To revise the 2017 classification of irreducible intertrochanteric fractures and summarize reduction techniques of 2021 classification.Methods:A retrospective analysis was conducted of the 17 patients with irreducible intertrochanteric fracture who had been treated at Department of Orthopaedic Surgery, The Ninth People's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine from January 2015 to December 2019. They were 7 males and 10 females, with an age of (73.2 ± 16.1) years. On the basis of 2017 classification, the irreducible intertrochanteric fractures were classified into 2 types in the present 2021 classification. Type Ⅰ were interlocking fractures which were further classified into 3 subtypes: type ⅠA were sagittal interlocking ones (7 cases), type ⅠB greater trochanter interlocking ones (one case) and type ⅠC lesser trochanter interlocking ones (one case). Type Ⅱ were separating fractures which were further classified into 4 subtypes: type ⅡA were sagittal separating ones (4 cases), type ⅡB coronal separating ones (one case), type ⅡC rotational separating ones(one case) and type ⅡD complete separating ones (2 cases). All patients were treated by closed reduction and intramedullary nailing with different reduction strategies corresponding to their fracture types (application of ejector rods, clamps or prying techniques, etc.). A total of 132 patients with reducible femoral intertrochanteric fracture who had been admitted during the same period were selected as the control group. The fracture reduction time, intraoperative blood loss and Harris hip score at the last follow-up were compared between the 2 groups.Results:The 2 groups were comparable because there was no significant difference in their preoperative general data ( P>0.05). Type ⅠA accounted for the highest proportion of irreducible intertrochanteric fractures [41.3% (7/17)], followed by type ⅡA [23.6% (4/17)]. The fracture reduction time [(44.6 ± 6.7) min] in the irreducible group was significantly longer than that in the control group [(39.2 ± 9.6) min] ( P<0.05). There was no significant difference in intraoperative blood loss or Harris hip score at the last follow-up between the 2 groups ( P>0.05). Conclusions:Compared with the "2017 classification" , the "2021 classification" is more concise and easy to remember, and can directly prompt the corresponding proper fracture reduction techniques. The patients with irreducible intertrochanteric fracture using proper reduction techniques can obtain functional recovery similar to that in the patients with reducible intertrochanteric fracture after reduction and fixation.

Objective    To evaluate the changes of ascending aortic (AA) diameter after transcatheter aortic valve replacement (TAVR), and evaluate the safety and efficacy of TAVR in patients with AA dilation. Methods    We retrospectively included 87 patients who underwent TAVR at our center from 2016 to 2019. These patients were divided into 2 groups based on the preoperative AA diameter. There were 17 patients in the AA diameter≥45 mm group (including 10 males, aged 74.4±5.6 years), and 70 patients in the AA diameter<45 mm group (including 39 males, aged 75.9±7.0 years). Results     The baseline variables were similar between two groups (P>0.05). The overall device success rate was 97.7% (85/87). The median computed tomography (CT) follow-up time was 24.2±11.8 months in patients with AA diameter≥45 mm and 23.0±10.7 months in patients with AA diameter<45 mm, and the median annual dilation rate of AA were 0.36 mm/year and 0.00 mm/year, respectively. No statistical significance was observed between two groups (P>0.05). No adverse aortic events occurred during the follow-up period. Conclusion    TAVR is safe and effective in patients with preoperative AA diameter≥45 mm, and the AA diameter remains stable after the procedure. Patients with preoperative AA diameter≥45 mm and AA diameter<45 mm have similar annual dilation rates.

Objective    To compare the perioperative results of hybrid coronary revascularization (HCR), off-pump coronary artery bypass (OPCAB) and percutaneous coronary intervention (PCI) in elderly patients with three-vessel coronary artery disease involving left anterior descending (LAD) branch and explores the safety of surgery. Methods    We prospectively enrolled patients with coronary heart disease over 65 years who were admitted to General Hospital of People’s Liberation Army from January 2018 to September 2019. Coronary angiography results were all three-vessel lesions involving the anterior descending artery. After preoperative examination and assessment by the cardiovascular team, all patients were suitable for OPCAB or PCI treatment. According to the patient’s preference, HCR, OPCAB or PCI were performed. The preoperative baseline data and perioperative results were collected, and SPSS 22.0 was used for statistical analysis. Results    A total of 110 patients met the criteria and were included in the study, 28 in the HCR group, 45 in the OPCAB group, and 37 in the PCI group, with an average age of 71.4±5.6 years. There was no statistical difference in the preoperative baseline data of patients among the three groups. The intubation time (P=0.039), perioperative drainage volume (P<0.001), blood transfusion (P=0.021) in the HCR group were lower than those in the OPCAB group. There was no statistical difference in the main organ adverse events (MOAE, P=0.096) and in-hospital mortality (P=0.784) among the three groups of patients. The use of antibiotics in the PCI group was significantly lower than the other two groups (P<0.001). Conclusion    HCR combines the advantage of CABG and PCI including proved long-term patency rate with left internal mammary artery-LAD grafting, less trauma and superior long-term patency with PCI in non-LAD territory. Compared with OPCAB and PCI, there is no increase in perioperative major organ adverse events and in-hospital mortality. It is a safe and reliable minimally invasive myocardial revascularization technique for elderly patients with three-vessel coronary artery disease involving the anterior descending artery.

To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L 
(P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.
Antipsychotic Agents ; adverse effects ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Double-Blind Method ; Dyslipidemias ; chemically induced ; drug therapy ; Humans ; Hypoglycemic Agents ; Metformin ; therapeutic use

Objective: To perform a retrospective analysis of the prognosis and influence factors of radiotherapy concurrent with che-motherapy and adjuvant temozolomide therapy in adult patients with high-grade brainstem glioma. Methods: Twenty-nine patients with pathological diagnosis of high-grade glioma (World Health Organization [WHO] Ⅲ and Ⅳ) from June 2012 to December 2013 were eligible for inclusion in the analysis. Demographic and clinical characteristics including age, gender, the time from morbidity to operation, the size of the lesion, the method of operation, the Karnofsky Performance Status (KPS) score, and the pathological grade were examined. The significance of related prognostic factors was evaluated via univariate and multivariate Logistic regression analy-sis. A P-value of<0.05 was considered to be statistically significant. Results: The median overall survival (OS) was 11.5 months. Univari-ate analysis showed that low WHO grade index was associated with better outcome (P<0.05). Multivariate analysis suggested that high KPS score (>60) and low WHO grade were associated with better survival. Conclusions: In this study, low pathological grade and high KPS score were independently associated with better survival among patients with high-grade brainstem glioma.

Objective To explore clinical classification and strategies for irreducible femur intertrochateric fractures.Methods A retrospective study was conducted of the 96 patients with irreducible intertrochanteric fracture who had been treated from January 2012 through December 2014 at our department.They were 47 men and 49 women,aged from 48 to 97 years (average,78.5 years).We classified the fractures according to location of fracture line and mechanism of fracture displacement into 5 types:13 cases of type Ⅰ (sagittal irreducible fracture),7 cases of type Ⅱ] (coronal irreducible fracture),72 cases of type Ⅲll (sagittal plus coronal irreducible fracture),zero of type Ⅳ (irreducible fracture involving the lesser trochanter),and 4 cases of type Ⅴ (irreducible fracture involving the greater trochanter).All the patients were managed using different techniques for closed reduction and fixation with proximal femoral nails antirotation Ⅱ.Results Of this series,limited open reduction was eventually conducted in 7.The operation time averaged 40 min;the amount of intraoperative blood loss averaged 200 mL.Fracture reduction was rated as grade Ⅰ in 78 cases and as grade Ⅱ in 18.The follow-up time averaged 16.6 months (from 12 to 24 months).All the fractures got united after an average of 5.8 months (from 3 to 9 months).The function of the affected hip was rated at the final follow-up using Harris scoring system as excellent in 79 cases and as good in 17,with an excellent to good rate of 100％.Refracture happened in one patient due to striking injury,urinary infection occurred in 2 patients and no wound infection was observed.Conclusion According to the classification and reduction strategy proposed by us,satisfactory reduction and fracture fixation can be achieved in management of irreducible intertrochanteric fractures.

Objective To investigate the effect of ursolic acid (UA) on the colorectal tumor and microenvironment in mice,and to provide a theoretical basis for the clinical application of UA.Methods The models of subcutaneous transplanted tumor of mouse CT26 cells was established.The models were divided into four groups:control group,tumor bearing group,tumor beating dimethyl sulfoxide (DMSO) group and tumor beating UA group.Tbe serum levels of interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay (ELISA).The number and percentage of myeloid-derived suppressor cell (MDSC) in the spleen of mice were analyzed by flow cytometry.The mRNA levels of IL-6 and signal transducer and activator of transcription 3 (STAT3) in tumor were examined by real-time quantitative polymerase chain reaction (RT-PCR).The protein levels of STAT3 and p-STAT3 in tumor were detected by Western blotting.Results The results showed that UA could significantly decrease the number of spleen MDSC.The accounts of spleen MDSC of tumor bearing UA group (249.60 ± 17.12) was lower than that of tumor beating DMSO group (366.40 ± 34.08),and the difference was statistically significant (P =0.021).The serum level of IL-6 in tumor bearing UA group [(46.40 ± 17.05) pg/ml] was decreased than that in tumor bearing DMSO group [(94.27 ±21.51) pg/ml],and the difference was statistically significant (P =0.012).The expression levels of IL-6 and STAT3 mRNA in tumor tissues of tumor bearing UA group (0.12 ±0.01,0.21 ±0.08) were lower than those of tumor bearing DMSO group (0.69 ± 0.14,0.79 ± 0.06),and the differences were statistically significant (P =0.008;P =0.003).The protein expression levels of STAT3 and p-STAT3 in tumor tissues of tumor bearing UA group (0.81 ±0.02,0.28 ±0.04) were lower than those of tumor bearing DMS0 group (0.98 ±0.02,0.91 ±0.22),and the differences were statistically significant (P =0.027;P =0.029).Conclusion UA may inhibit the activation of STAT3 signaling pathway and the amplification of MDSC in microenvironment by reducing IL-6,thus to enhance the function of immune-killing tumor cells to regulate tumor immune microenvironment and inhibit the immune escape of mouse colorectal cancer cells.

Objective To investigate the clinical effect of mild hypothermia on neonatal bilirubin encephalopathy, and the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT and amplitude integrated electroencephalogram (aEEG) for diagnosis and evaluation of curative effect. Methods From May, 2013 to December, 2014, 29 newborns with bilirubin encephalopathy were divided into conventional group (n=15) and mild hypothermia group (n=14). The conventional group received conventional therapy, and the other group received mild hypothermia in addition. The aEEG and neuron-specific enolase (NSE) were measured before and after treatment, as well as the glucose metabolism rate with 18F-FDG PET/CT after treatment. Results The NSE was lower after treatment in both groups (t>9.670, P<0.001), and was lower in the mild hypothermia group than in the conventional group (F=46.146, P<0.001). After treatment, sleep-wake cycle (SWC), epileptiform activity and the degree of abnormality were obviously improved (P<0.05), and were better in the mild hypothermia group than in the conventional group (P<0.05). The cerebral glucose metabolism rate was significantly better in the mild hypo-thermia group than in the conventional group (t>2.943, P<0.01). The cerebral glucose metabolism rate was negatively correlated with aEEG and NSE (r>0.640, P<0.05). Conclusion Mild hypothermia therapy could further promote the energy metabolism of brain cells in neonatal bilirubin encephalopathy. 18F-FDG PET/CT and aEEG can be used for early diagnosis and therapeutic evaluation.