In recent years, liver cancer stem cells (LCSC) have been considered one of the main causes of treatment failure and recurrence of hepatocellular carcinoma (HCC). Many studies have shown that LCSC are a small fraction of cells with the abilities of self-renewal, differentiation, and tumorigenesis in HCC tumor, which can initiate the onset of HCC and affect its proliferation, invasion, metastasis, recurrence, and drug resistance. Therapies based on tumor microenvironment (TME) have been developed recently, and a number of studies have found that targeting the relevant elements of TME has a higher therapeutic value than targeting tumor cells themselves. TME is the microenvironment for the growth of LCSC and HCC cells, and it interacts with LCSC and has a synergistic effect, thereby playing a positive role in the development and progression of HCC. This article introduces how various cellular components and non-cellular components in TME interact with LCSC to regulate the development and progression of the HCC. In addition, this article also describes the molecular targets, therapies, and drugs associated with the main components of TME and LCSCs, in order to seek safer and more effective targeted therapies for HCC.

AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P＜0.05 or P＜0.01),significantly increased mean alveolar number and PEF(P＜0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P＜0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P＜0.05 or P＜0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P＜0.05 or P＜0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.

Objective:To analyze the relationship between blood electrolytes and the prognosis of patients with severe coronavirus disease 2019 (COVID-19) and to provide assistance for clinical decision-making.Methods:The clinical data of patients with severe COVID-19 admitted to intensive care unit (ICU) of the Wuhan Third Hospital by the Shanghai aid-Hubei medical team from January 21 to March 4, 2020 were collected. Excluding ineligible patients, 110 patients were finally enrolled. The patients' gender, age, temperature, heart rate, systolic and diastolic blood pressure, clinical symptoms at admission, time of symptom onset, duration of fever, and relevant indicators at admission to ICU (including blood potassium, chloride, sodium, calcium, phosphorus, and magnesium, etc.) and prognosis were analyzed. The patients were grouped by blood potassium or calcium levels or blood potassium/calcium ratio. The Kaplan-Meier survival curves were used to analyze the survival of patients in each group. The relationship between the potassium/calcium ratio and the prognosis was analyzed using restricted cubic spline plots. The relationship between each index in the different models and the prognosis was analyzed using Cox regression models.Results:Among 110 severe COVID-19 patients, 78 cases survived, and 32 cases died. Compared with the surviving group, patients in the death group had higher blood potassium levels [mmol/L: 4.25 (3.80, 4.65) vs. 3.90 (3.60, 4.20), P < 0.05] and lower blood calcium levels (mmol/L: 2.00±0.14 vs. 2.19±0.18, P < 0.05). The Kaplan-Meier survival curves showed that patients in the potassium > 4.2 mmol/L group had a worse prognosis than the potassium < 3.8 mmol/L group and the potassium 3.8-4.2 mmol/L group ( P = 0.011), patients in the calcium > 2.23 mmol/L group had a better prognosis than the calcium < 2.03 mmol/L group and the calcium 2.03-2.23 mmol/L group, and the lower calcium group had a worse prognosis ( P = 0.000 15). Cox regression analysis showed that the hazard ratio ( HR) of blood potassium and calcium were 2.08 and 0.01, respectively, in model 1 (single blood potassium or calcium) and in model 2 (model 1 plus age and gender), the HR of blood potassium and calcium were 1.98 and 0.01 respectively, which were significantly associated with patient prognosis (all P < 0.05). Patients in the group with the potassium/calcium ratio > 1.9 had higher blood potassium levels and a higher proportion of mechanical ventilation, lower calcium levels and lower proportion of survival, and longer time of ICU admission compared with the groups with the potassium/calcium ratio < 1.7 and 1.7-1.9. The Kaplan-Meier survival curves showed that the survival rate of the potassium/calcium ratio > 1.9 group was the lowest ( P < 0.000 1), and there was no statistically significant difference in survival between the potassium/calcium ratio < 1.7 group and the potassium/calcium ratio 1.7-1.9 group. A restricted cubic spline plot corrected for age and gender showed that patients in the potassium/calcium ratio > 1.8 group had HR values > 1. Cox regression analysis corrected for other indicators showed that the potassium/calcium ratio was still associated with patient prognosis ( HR = 4.85, P = 0.033). Conclusions:Blood potassium, calcium, and the potassium/calcium ratio at ICU admission are related to the prognosis of patients with severe COVID-19, and the potassium/calcium ratio is an independent risk factor for the death of patients. The higher the potassium/calcium ratio, the worse the prognosis of patients.

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Objective:To study the Epstein-Barr virus (EBV) activity and its clinical characteristics in patients with hemorrhagic fever with renal syndrome (HFRS). Methods:From January 2016 to August 2017, patients with HFRS who were hospitalized in the First Affiliated Hospital of Harbin Medical University were routinely tested by EBV serology, and were divided into two groups according to their presence or absence of EBV infection, namely EBV active group and non-EBV active group. The clinical data between the two groups were compared and analyzed by SPSS 18.0.Results:A total of 188 HFRS patients were enrolled, including 73 cases in EBV active group and 115 cases in non-EBV active group. The EBV active rate of HFRS patients was 38.83% (73/188). The incidences of lumbago [57.53% (42/73) vs 42.61% (49/115)], abdominal pain [42.47% (31/73) vs 20.00% (23/115)], skin and mucosa congestion [57.53% (42/73) vs 39.13% (45/115)], and conjunctiva edema [50.68% (37/73) vs 28.70% (33/115)] in EBV active group were significantly higher than those in non-EBV active group (χ 2 = 3.983, 11.008, 6.083, 9.239, P < 0.05). There were 10, 7 and 43 patients with acute kidney injury (AKI) stage 1, 2 and 3 in EBV active group and 5, 13 and 53 patients in non-EBV active group. Degree of AKI in EBV active group was higher than that in non-EBV active group, and the difference was statistically significant (χ 2 = 12.615, P < 0.05). In EBV active group, the proportion of patients whose renal function recovery over 15 days [23.29% (17/73)] and white blood cell count [11.26 (3.39 ~ 54.23) × 10 9/L] were significantly higher than those in non-EBV active group [6.96% (8/115), 10.03 (2.91 ~ 66.99) × 10 9/L], and the differences were statistically significant (χ 2 = 10.330, Z = - 2.003, P < 0.05). Conclusion:HFRS patients may cause latent EBV activity, complicate their clinical features, cause severe renal damage and prolong the recovery time of renal function.

Pain is the most fearful symptom in cancer patients.The cancer patients suffered refractory pain with the progress of cancer.Not all cancer patients could obtain adequate pain relief by the mefhod of three-step pain relief ladder of WHO.With the reseach and recognition of the mechanisms,the pain can be effectively controlled by the right technique at the right time.It is summarized in this artical about the central and peripheral mechanism and the treatment progress of the terminal cancer pain.

Objective To select sonogram features for the differential diagnosis of benign and malignant thyroid small nodules by Logistics regression analysis,and to contribute the binary Logistic regression model of sonogram features as independent variable and evaluate the value of conventional ultrasonography and ultrasound elastography (UE) in the differential diagnosis of benign and malignant thyroid small nodules.Methods 166 thyroid nodules (≤ 10 mm) in 140 patients were reviewed and analyzed by 2D ultrasound,color Doppler flow imaging and UE.A Logistic model was obtained based on pathology as golden diagnosis criteria.The odds ratio of variables in the equation were compared to assess various variables,especially the efficacy of elastography in the diagnosis.Results Four statistically significant features were finally entering the Logistic stepwise regression model,including shape,calcification,the internal component of nodules and elasticity score.And the odds ratio of the elasticity score was higher than other features.Conclusions The analysis of binary Logistic regression can select the valuable variables for the diagnosis of pathological nature of thyroid small nodules.UE has much more dominances than other features.The combinated application of UE and 2D ultrasonic features plays a great clinical role in the final diagnosis of thyroid small nodules.

Objective To investigate the expression of cystein rich 61 (Cyr61) and vascular endothelial growth factor (VEGF) in different stages of multiple myeloma (MM) patients,evaluate their relationship with angiogenesis and prognosis,and to determine the relationship between Cyr61 and VEGF.Methods Expression of Cyr61 and VEGF in BMMNC from 31 patients with different stages of MM and 10 cases of control were detected by RT-PCR.Results Expression of Cyr61 and VEGF in patients with MM (0.3652±1.5423,0.4815±1.3423) were significantly elevated in comparison to control (0.1862±0.7542,0.2012±1.2331) (P ＜ 0.05,P ＜ 0.01).Expression of Cyr61 and VEGF in stage Ⅲ (0.4632±0.1634,0.5356± 0.2342) was significantly higher than those in stage Ⅰ and stage Ⅱ (t =2.423,2.524,P ＜ 0.05),but there was no difference between stage Ⅰ and stage Ⅱ (0.2513±0.1365,0.3064±0.2124; 0.3084±0.2254,0.3653±0.1265) (t =1.782,1.824,P ＞ 0.05).The levels of Cyr61 and VEGF were significantly decreased after chemotherapy compared to before chemotherapy (P ＜ 0.01).Expression of Cyr61 and VEGF were positively correlated (r =0.8941,P ＜ 0.01).Conclusion Cyr61 and VEGF may play roles in the angiogenesis and pathophysiology of MM.It can be used to guide treatment and estimate prognosis by monitoring Cyr61 and VEGF.

Objective To study the significance of discrimination of scarce cardiac masses by echocardiography. Methods Twenty-nine patients with cardiac masses selected randomly were examined by transthoracic echocardiography and transesophageal echocardiography to observe their shape, internal echo, margins, membrane and blood flow. Results Twenty-three patients in twenty-nine cases were confirmed by surgery and pathology including eight benign masses and fifteen malignant masses, but the other six patients with metastasis carcinoma had no pathologic results. Eighteen patients got correct diagnosis, nine patients weren′t diagnosed in character and two patients were made a wrong diagnosis. Conclusions Echocardiography is the only noninvasive method which can provide reliable evidences for clinic before surgery to discriminate scarce cardiac masses.