Objective:To explore whether thyroxine (T 4) could promote differentiated thyroid cancer (DTC) progression by binding to integrin α vβ 3in vitro and its downstream mechanism. Methods:Papillary thyroid cancer cell lines TPC-1, K1 and follicular thyroid cancer (FTC) cell line FTC133 were cultured in vitro, and the expressions of integrin α vβ 3 in those 3 DTC cell lines were determined with immunofluorescence and flow cytometry analysis. After the treatment of T 4, tetraiodo thyroacetic acid (Tetrac) and Arg-Gly-Asp (RGD) peptide alone or in combination, the proliferation and metastatic potential of DTC cell lines were detected by cell counting kit-8 (CCK-8), Transwell migration and invasion assays. The small interfering RNA (siRNA) transfection was used to verify whether integrin α v or β 3 subunit knockdown could reverse the effect of T 4 on DTC cells. The expression levels of downstream signaling proteins phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and total extracellular signal-regulated kinase (ERK)1/2 were detected by Western blot. The effects of mitogen-activated protein kinase kinase (MEK)1/2 inhibitor (GSK1120212) on the proliferation, migration and invasion of T 4-treated cells were detected. One-way analysis of variance and Tukey test were used for data analysis. Results:The integrin α vβ 3 expressions in TPC-1, K1 and FTC133 cells were all positive, with the relative mean fluorescence intensity (MFI) of 61.93±18.61, 16.89±2.43 and 32.36±0.83, and the percentages of positive cells of (94.38±1.30)%, (74.11±3.87)% and (50.67±1.78)%, respectively ( F values: 13.36 and 217.30, P=0.006 and P<0.001). Compared with control group, the proliferation, migration and invasion in the three DTC cell lines treated with T 4 were significantly enhanced (96 h, F values: 62.67-297.50, q values: 13.15-20.73, all P<0.001). T 4-induced cell proliferation, migration and invasion were markedly reversed by Tetrac or RGD (96 h, q values: 8.61-17.54, all P<0.001). T 4-induced cell proliferation, migration and invasion were also significantly inhibited by the knockdown of integrin α v or β 3 subunit (72 h, F values: 7.75-70.98, q values: 4.77-15.21, all P<0.05). Western blot results showed that the phosphorylation levels of ERK1/2 in DTC cells were significantly increased by T 4 treatment, and the T 4-induced activation of ERK1/2 signaling pathway could be blocked by Tetrac, RGD, integrin α v or β 3 subunit knockdown. T 4-induced cell proliferation, migration and invasion were significantly reversed by GSK1120212 (96 h, F values: 47.53-151.40, q values: 10.32-16.65, all P<0.001). Conclusion:T 4 can promote cell proliferation and metastasis of DTC cells by binding to integrin α vβ 3 and activating the ERK1/2 pathway.

OBJECTIVE: To develop a self deep breathing training device which can improve lung function compliance and blood oxygen saturation. METHODS: The device consists of four parts:flow tube, measuring cylinder, mobile phone holder and meridian guidance audio-visual synthesis training software. The flow tube measures the flow rate of inhaled gas, the metering cylinder measures the total amount of inhaled gas, and the mobile phone rack is equipped with a mobile phone storing the meridian guidance audio-visual synthesis training software. RESULTS: The device is reasonable in structure and flexible in operation, which can meet the requirements of self deep inspiration training under the guidance of training module. CONCLUSIONS Deep inspiration training under the guidance of guidance training module can form "deep and slow" abdominal breathing, and then improve lung function.
Cell Phone ; Lung ; Meridians ; Software

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective: To observe the survival and side effects of stereotactic body radiotherapy (SBRT) in large hepatocellular carcinoma (HCC) patients. Methods: Twenty-eight large HCC patients undergoing SBRT in 302 Military Hospital from November 1, 2011 to January 31, 2014 were observed. The prescribed dose was 39-61 Gy/3-9f. Among them, 20 patients simultaneously received transcatheter arterial embolization. The overall survival (OS), progression-free survival (PFS) and local control (LC) rates were calculated by using Kaplan-Meier method. The influencing factors of OS were analyzed by Cox regression model. The influencing factors of radiation-induced liver disease (RILD) were identified by using Logistic regression analysis. Results: The 1-, 2-, 3-and 5-year OS rates were 75%, 57%, 54% and 22%, respectively. The 1-, 2-, 3-and 5-year PFS rates were 59%, 47%, 36% and 18%, respectively. The 1-, 2-, 3-and 5-year LC rates were 92%, 86%, 86% and 86%, respectively. Four patients suffered from RILD and none died from RILD. Child-Pugh classification was the influencing factor of OS and RILD. Conclusion It is preliminarily believed that SBRT is an alternative and safe treatment for patients with large HCC.

OBJECTIVE: To observe the difference for vascular dementia among flipping moxibustion of medicine at acupoints in governor vessel combined with acupuncture, simple medicine and simple acupuncture. METHODS: A total of 120 patients with vascular dementia were randomly assigned into a combination group, a flipping moxibustion group and an acupuncture group, 40 cases in each one, with 2 patients dropping respectively. Flipping moxibustion was used at the acupoints of group A on Monday and at the acupoints of group B on Friday in the flipping moxibustion group. The acupoints of group A were Baihui (GV 20), Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Jizhong (GV 6), Mingmen (GV 4), Yaoyangguan (GV 3), and the acupoints of group B were Fengfu (GV 16), Taodao (GV 13), Shendao (GV 11), Jinsuo (GV 8), Xuanshu (GV 5), Changqiang (GV 1). Acupuncture was used in the acupuncture group at the main acupoints of Baihui (GV 20), Sishencong (EX-HN 1), Neiguan (PC 6), Zusanli (ST 36), Taixi (KI 3) and Xuanzhong (GB 39), matched with the acupoints based on syndrome differentiation, 30 min a time, once a day, continuous 5 times a week. The above two methods were applied in the combination group. All the treaments were for 4 weeks. The indexes were observed before and after treatment, including syndrome differentiationof TCM scale for vascular dementia (SDSVD), simple mental state scale (MMSE), self-care ability of daily life scale (ADL). The clinical effects and safety were evaluated. RESULTS: After treatment, the total effective rate in the combination group was 89.5% (34/38); the rate in the flipping moxibustion group was 65.8% (25/38); the rate in the acupuncture group was 63.2% (24/38). The difference among groups was statistically significant (<0.05). The effect in the combination group was better than those in the flipping moxibustion group and in the acupuncture group (both <0.05). There was no statistically significant difference between the flipping moxibustion group and the acupuncture group (>0.05). The SDSVD scores after treatment were lower and the MMSE and ADL scores after treatment were higher than those before treatment in the three groups (all <0.01), with better results on the above three scores in the combination group than those in the other two groups (<0.05, <0.01), and the differences on the three scores between the flipping moxibustion group and the acupuncture group were not statiatically significant (all >0.05). The treatment in the three groups was safe, without stastical significance (>0.05). CONCLUSION The effect of flipping moxibustion combined with acupuncture for vascular dementia is better than those of simple flipping moxibustion and simple acupuncture. The combination treatment achieves better effect on TCM syndrome, cognitive function and daily activity ability than the other two simple treatment.
Activities of Daily Living ; Acupuncture Points ; Dementia, Vascular ; Humans ; Moxibustion

Objective To understand the influence of family integrated care (FICare) model to the human breastfeeding rate of preterm infants in neonatal intensive care units (NICUs).Method It is a multicenter cluster randomized controlled trail for intervention and prognosis.According to inclusion and exclusion criteria,preterm infants with gestation age 28 ～ 35 weeks in 9 NICUs of tertiary hospitals in 8 provinces in China were enrolled and divided into FICare and control group.Mothers of FICare infants were invited to stay in NICU ward at bedside for no less than 3 hours per day.Under the supervision of nurses,FICare infants'mothers complete 13 items of infants'caring skills including Six-step Hand Washing and hand hygiene,positioning the baby,changing diapers and estimating urine output,skin and mouth caring,kangaroo care and so on.The primary outcome is the human breastfeeding rate.Secondary outcomes include feeding parameters and FICare-related parameters.SPSS 20.0 software is used for the data analysis.Result (1) There were 212 infants and 215 infants enrolled in FICare group and control group,respectively.There was no significant difference between 2 groups in gender,gestational age,birth weight (BW),Z-score of BW,singleton percentage,antenatal steroid completion,diagnosis,day of life (DOL) for starting feeds (P ＞ 0.05).(2) There was no significant difference between 2 groups in DOL for full feeding (P ＞ 0.05).The median age of starting breastfed in both groups was DOL 4.There were 202 cases (87.3％) in FICare group and 80 cases (34.9％) in control group be successfully breastfed.The rate of formula feeding,incidence of nosocomial infection,DOL for regaining BW,decrease of BW AZ score in FICare group was significantly lower than the control group,and the weight gain velocity after regaining BW in FICare group was significantly higher than the control group (P ＜ 0.05).(3) The implementation of FICare and completion of antenatal steroid were the independent protective factors for breastfeeding (OR =27.703,95％ CI 14.531 ～ 52.816;OR =9.496,95％ CI 4.768 ～ 18.912),while nosocomial infection and delayed DOL for starting breastfeeding were the independent risk factors for breastfeeding (OR =0.380,95％CI 0.182 ～0.795;OR =0.847,95％ CI 0.734 ～0.977).Conclusion FICare is significantly beneficial to the breastfeeding rate of preterm infants in NICUs.FICare may decrease the severity of extrauterine growth retardation.

Objective To study the cytotoxicity of bi-chimeric antigen receptors modified T lymphocytes (BiCAR-T) on the human acute myeloid leukemia (AML) cell line HL60 in vitro and the anti-tumor effects of BiCAR-T on the NOD SCID mouse model of AML in vivo.Methods The BiCAR-T were prepared and the expression of chimeric antigen receptor (CAR) of prepared BiCAR-T was analyzed by flow cytometry.In vitro study was divided into two groups:the experiment group (BiCAR-T) and the control group (T lymphocyte).The killing rate of BiCAR-T in vitro on HL60 cells was determined by CCK8 assay and the level of interferon-γ (IFN-γ) secreted from BiCAR-T co-culturing with HL60 cells for 48 hours was detected by enzyme linked immunosorbent assay (ELISA) at different effect/target ratios (5∶1,10 ∶ 1,20 ∶ 1).The NOD SCID mice AML model was established by the injection of HL60 cells through tail vein and used to assess the antitumor effects in vivo.The mice were randomly divided into three groups according to the random number table:the blank control group receiving 0.9％ NaCl 0.2 ml through tail vein,the model group and the treatment group receiving 1 × 107 HL60 cells in 0.2 ml phosphate buffer saline (PBS).After 20 days,the treatment group was injected with 2 × 107BiCAR-T in 0.2 ml PBS 3 times a week for 2 weeks,while the other two groups received 0.9％ NaCl 0.2 ml.The pathological changes in the mice livers and spleens were observed after 2 weeks of treatment.Results The CAR expression rates of BiCAR-T were more than 50.00％.In vitro experiments proved that the killing rates of BiCAR-T in the experimental group and T lymphocytes in the control group on HL60 cells were (25.43 ±1.32)％ vs.(16.18 ±0.75)％,(50.33±3.11)％ vs.(25.47±1.27)％,and (85.89 ± 3.96) ％ vs.(49.45 ± 2.77) ％ at different effect/target ratios (5 ∶ 1,10 ∶ 1,20 ∶ 1).The killing efficiency of BiCAR-T and T lymphocytes on HL60 cells was significantly different (F =404.17,P ＜ 0.001);the killing efficiency of BiCAR-T and T lymphocytes on HL60 cells was significantly different at different effect/ target ratios (F =548.09,P ＜ 0.001);and the killing efficiency on HL60 cells in the experimental group (BiCAR-T) was significantly higher than that in the control group (T lymphocytes) at different effect/target ratios (F =45.36,P ＜ 0.001).The IFN-γlevels secreted from BiCAR-T in the experiment group and T lymphocytes in the control group co-culturing with HL60 ceils after 48 h were (435.65 ± 20.44) pg/ml vs.(356.75 ± 19.87) pg/ml,(1 639.98 ± 95.75) pg/ml vs.(1 109.37 ± 80.98) pg/ml,and (3 467.43 ± 187.54)pg/ml vs.(2 245.52 ± 112.66)pg/ml.The IFN-γlevel in the experiment group (BiCAR-T) and the control group (T lymphocytes) was significantly different (F =156.24,P ＜ 0.001);the IFN-γ level was significantly different at different effect/target ratios (F =857.67,P ＜ 0.001);the IFN-γlevel in the experimental group (BiCAR-T) was significantly higher than that in the control group (T lymphocytes) at different effect/ target ratios of 5 ∶ 1,10 ∶ 1,20 ∶ 1,respectively (F =46.31,P ＜ 0.001).The result of hematoxylineosin staining (HE) staining showed that leukocyte infiltration in the treatment group was significantly decreased compared with the model group.Conclusion The experimental results showed that BiCAR-T is a kind of efficient targeted immunocyte modified by gene engineering,and it can significantly inhibit leukocyte infiltration of AML in vivo and in vitro.

Objective Evaluate the interaction between dexmedetomidine and propofol for seda-tion induction.Methods Seventy-five patients who undergoing elective surgery under general anesthe-sia,36 males and 39 females,aged 18-65 years,BMI 20-25 kg/m2,ASA physical status Ⅰ or Ⅱwere randomly divided into three groups (n=25 ):propofol group (group A),dexmedetomidine group (group B),propofol combined dexmedetomidine group(group C),each group was divided into 5 groups according to different drug doses,the dose ratio of the adjacent two groups was 1.25,and the median effective dose (ED50)value was calculated by the point oblique method.Results The hyp-notic dose of propofol ED50in group A was 1.25 mg/kg (0.90-1.45 mg/kg),and the anesthetic induction dose of dexmedetomidine ED50in group B was 1.35 μg/kg (0.95-1.50 μg/kg),and the hypnotic dose of propofol and dexmedetomidine ED50in group C was 0.65 mg/kg (0.50-0.90 mg/kg)and 0.40 μg/kg (0.34-0.65 μg/kg)respectively.Conclusion Dexmedetomidine combined with propofol can produce a sig-nificant hypnotic effect,while reducing the impact on the circulation.

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.