Objective To analyze the efficacy and safety of catheter-directed thrombolysis (CDT) for acute lower extremity deep venous thrombosis (DVT) in patients aged 70 years and over.Methods Clinical data of 109 cases who had acute lower extremity DVT and had been treated with CDT from March 2011 to September 2014 were retrospectively analyzed.Results Inferior vena cava filters (IVCF) were implanted in 109 patients.A thrombolytic catheter was inserted from the contralateral femoral vein (21 cases),ipsilateral popliteal vein (44 cases),posterior tibial vein (28 cases) or small saphenous vein (16 cases).The duration of thrombolysis was (5.47±2.13) d.The dosage of urokinase was (3.80 ± 0.56) million units.Forty-two cases underwent balloon dilatation alone,and 67 cases combined balloon dilatation with stent implantation.Gingival bleeding occurred in 7 patients and gross hematuria occurred in 4 patients during thrombolysis,which disappeared after medication adjustment.No symptomatic pulmonary embolism (PE) or other serious complications were found in any patients.There were significant differences in the venous patency score and lower limb circumferences at 10 cm above and below the knee one week after treatment (t=3.874,P=0.031).Ninety-seven cases were followed up for a mean period of (20.76.5) months,and the vein patencyrate was (77.9± 10.5) ％ and (73.1±9.4) ％ at 6 and 18 months after treatment,respectively.Recurrence of deep vein thrombosis was found in 6 cases,of which 2 cases had recurrent stent thrombosis,and treatment with CDT again was successful.No severe deep venous thrombosis syndrome (PTS) was found during the follow-up.Conclusions CDT is a minimally invasive procedure and can rapidly resolve limb venous drainage disorders.CDT is safe,has few complications and usually generates satisfactory outcomes.For very-old elderly patients who have no anticoagulation and thrombolytic contraindications,CDT is a useful option for the treatment of acute lower limb DVT.

Objective To investigate the role of neuroglobin ( NGB) in oxygen-glucose deprivation and reoxygenation ( OGD/R ) induced mitochondrial depolarization and reactive oxygen species ( ROS ) production in a human neuroblastoma cell line (SH-SY5Y).Methods SH-SY5Y cells were transfected with lentivirus to establish a stable cell line of NGB knockdown ( KD).After treated with OGD/R, cells were collected at different time points to analyze NGB mRNA and protein levels.Furthermore, cells were stained with JC-1 and DCFH-DA to evaluate mitochondrial depolarization and ROS production by inverted fluorescence microscope.Also, to determine the neurotoxicity , we measured the lactate dehydrogenase ( LDH) level in the cell culture medium.Results After the treatment of OGD/R, the NGB mRNA and protein started to elevate and peak at 4 h and 8 h (2.04 ±0.35 fold,1.69 ±0.18 fold).Compared with the vector group , NGB KD group had much more mitochondrial depolarization [ JC-1 red/green ( 1.10 ±0.10 ) vs (1.46 ±0.11),P<0.05] and ROS production [DCFH-DA fluorescence (36.30 ±5.32) vs (16.26 ± 2.97),P<0.05].Furthermore, NGB KD groups had a higher level of LDH release [(63.42 ±6.14)%vs (49.65 ±5.09 )%, P <0.05 ].Conclusions NGB plays an important role in the homeostasis of mitochondria.Knockdown of NGB results in increased mitochondrial depolarization , ROS production and neurotoxicity under hypoxia circumstances.

Objective:To observe the effect of early mechanical ventilation on the expression of inflammatory factors and prognosis of patients with severe traumatic brain injury (sTBI).Methods:From January 2017 to December 2020, 138 patients with sTBI admitted to the department of the emergency of Xinhua Hospital Chongming Branch were enrolled. Although some patients were admitted to hospital without acute respiratory failure, their Glasgow coma score (GCS) were less than 8, they bad risk of hypoxia, so early mechanical ventilation was required. According to the patient's condition and the willingness of family members, patients were divided into mechanical ventilation group (tracheal intubation mechanical ventilation) and conventional oxygen inhalation group (nasal catheter or mask oxygen inhalation) in the end. The arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), tumor necrosis factor-α (TNF-α), and interleukin (IL-6, IL-10) levels at admission, preoperation and 72 hours postoperation, as well as GCS before operation and 1 week after operation, the duration and number of patients successfully evacuated from the ventilator within 1 week after surgery were observed and analyzed. Results:A total of 138 sTBI patients were enrolled in the study, including 72 cases in the mechanical ventilation group and 66 cases in the routine oxygen inhalation group. In the two groups, PaO 2, PaO 2/FiO 2 and IL-10 were higher, and PaCO 2, TNF-αand IL-6 were lower at 72 hours post operation than that before operation. Moreover, the changes in the mechanical ventilation group were more significant than those in the conventional oxygen inhalation group [PaO 2 (1 mmHg = 0.133 kPa): 94.6±7.7 vs. 92.5±6.8, PaO 2/FiO 2 (mmHg): 351±94 vs. 319±89, IL-10 (ng/L): 8.2±2.7 vs. 7.4±1.8, PaCO 2 (mmHg): 35.6±1.8 vs. 37.5±2.7, TNF-α(ng/L): 71.5±6.3 vs. 96.8±15.5, IL-6 (ng/L): 10.8±3.9 vs. 14.4±6.5, all P < 0.05]. There were 17 patients with severe respiratory insufficiency or failure in the conventional oxygen inhalation group before operation. Compared with the conventional oxygen inhalation group, the GCS score (11.7±3.1 vs. 9.1±4.6) and the proportion of successful weaning [62.5% (45/72) vs. 44.0% (29/66)] were significantly higher, and the duration of successful weaning (hours: 63.5±28.6 vs. 88.1±33.9) was significantly shorter in the mechanical ventilation group 1 week after operation. Conclusion:Early mechanical ventilation in sTBI patients can significantly improve oxygen supply, inhibit the release of pro-inflammatory factors, reduce secondary brain damage, and effectively improve the prognosis.

Obesity is one of the most challenging global public health issues, and more than half of adults in Chia are overweight or obese. Obesity has been shown to be a risk factor for type 2 diabetes, cardiovascular disease, colon cancer and other specific cancers, and has become a serious threat and even a danger to the health and quality of life of the nation. With the mature development of bariatric surgery in the last 20 years, it is now widely recognized for its effectiveness and safety in the treatment of obesity and related metabolic diseases, as well as improving patients′ life expectancy and quality of life. However, previous data from the literatures suggest that some patients require revisional surgery after bariatric surgery, with the incidence of revisional bariatric surgery as 5% to 50%. The main reasons for revisional bariatric surgery are poor post-operative outcomes, including the lack of significant weight loss, weight regain and no significant improvement or even recurrence of associated metabolic disease, and other reasons include the development of anaemia, malnutrition and long-term chronic pain. Currently, there is only the East Asian expert consensus on revised bariatric surgery proposed by Chinese Society for Metabolic & Bariatric Surgery in 2018. However, there are still no uniform standards regarding the indications, contraindications and surgical modalities of revisional bariatric surgery in clinical practice. The authors summarize the latest researches of revisional bariatric surgery, in order to provide the guidance value for clinical practice.

Objective:To explore whether the degree of skeletal muscle atrophy in obese individuals under the influence of colorectal cancer is more severe than that in non-obese individuals.Methods:The clinical data of patients who underwent radical resection of colorectal cancer in our department from Jul 2020 to Dec 2021 was collected. Sixty-four obese patients were included and 64 non-obese patients were matched according to propensity score. At the same time, 51 obese patients were collected from non-tumor patients and matched with 51 non-obese patients. The psoas muscle index (PMI) of included patients was analyzed and compared.Results:The PMI of patients with colorectal cancer was significantly lower than that of corresponding non-tumor patients, regardless of gender and body weight (both P<0.05). The PMI of obese patients with colorectal cancer was significantly lower than that of non-obese patients ( P<0.05). Conclusions:The impact of colorectal cancer on skeletal muscle atrophy in obese individuals is greater than that in normal weight individuals. Therefore, the skeletal muscle status of obese patients with colorectal cancer should be evaluated more comprehensively.

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

OBJECTIVE: To investigate the molecular mechanism underlying the inhibitory effect of aloin on the proliferation and migration of gastric cancer cells. METHODS: Human gastric cancer MGC-803 cells treated with 100, 200 and 300 μg/mL aloin were examined for changes in cell viability, proliferation and migration abilities using CCK-8, EdU and Transwell assays. HMGB1 mRNA level in the cells was detected with RT-qPCR, and the protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 were determined using Western blotting. JASPAR database was used to predict the binding of STAT3 to HMGB1 promoter. In a BALB/c-Nu mouse model bearing subcutaneous MGC-803 cell xenograft, the effect of intraperitoneal injection of aloin (50 mg/kg) on tumor growth was observed. The protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 in the tumor tissue was examined using Western blotting, and tumor metastasis in the liver and lung tissues was detected using HE staining. RESULTS: Treatment with aloin concentration-dependently inhibited the viability of MGC-803 cells (P < 0.05), significantly reduced the number of EdU-positive cells (P < 0.01), and attenuated the migration ability of the cells (P < 0.01). Aloin treatment dose-dependently down-regulated HMGB1 mRNA expression (P < 0.01), lowered the protein expressions of HMGB1, cyclin B1, cyclin E1, MMP-2, MMP-9 and p-STAT3, and up-regulated E-cadherin expression in MGC-803 cells. Prediction based on JASPAR database suggested that STAT3 could bind to the promoter region of HMGB1. In the tumor-bearing mice, aloin treatment significantly reduced the tumor size and weight (P < 0.01), lowered the protein expressions of cyclin B1, cyclin E1, MMP-2, MMP-9, HMGB1 and p-STAT3 and increased the expression of E-cadherin in the tumor tissue (P < 0.01). CONCLUSION Aloin attenuates the proliferation and migration of gastric cancer cells by inhibiting the STAT3/HMGB1 signaling pathway.
Humans ; Animals ; Mice ; Stomach Neoplasms ; Cyclin B1 ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; HMGB1 Protein ; Signal Transduction ; Cell Proliferation ; STAT3 Transcription Factor