Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and tension.These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes,shaping the microenvironment and maintaining cellular physiological balance.Several studies have demonstrated the roles of Yes-associated protein(YAP)and its homolog transcriptional coactivator with PDZ-binding motif(TAZ)as mechanotransducers,exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis.This regulatory function entails the involvement of the cytoskeleton,nucleoskeleton,integrin,focal adhesions(FAs),and the integration of multiple signaling pathways,including extracellular signal-regulated kinase(ERK),wingless/integrated(WNT),and Hippo signaling.Furthermore,emerging evidence substantiates the implication of long non-coding RNAs(lncRNAs)as mechanosensitive molecules in cellular mechanotransduction.In this review,we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical stimuli.Additionally,we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.

Objective To evaluate the relationship between sevoflurane-induced cognitive impairment and α1B adrenoceptors (ADRA1B) and ADRA1D in the cerebral cortex of rats.Methods Forty-eight SPF adult Sprague-Dawley rats (half male,half female),weighing 220-260 g,were divided into control group (C group,n =24) and sevoflurane group (S group,n =24) using a random number table method.Group C and group S inhaled air and 3％ sevoflurane,respectively,for 5 h.Eight rats in each group were sacrificed immediately after anesthesia,and the cerebral cortex was removed.Eight rats in each group were selected on days 1 and 7 after anesthesia and underwent Barnes maze test.The rats were then sacrificed,and the cerebral cortex was removed.The expression of ADRA1B and ADRA1D protein and mRNA in cerebral cortex tissues was detected by Western blot and fluorescent quantitative real-time polymerase chain reaction,respectively.Results Compared with group C,the number of entering incorrect holes was significantly increased at 1 and 7 days after anesthesia,the latency and total distance to enter the target hole were prolonged,and the expression of ADRA1B and ADRA1D protein and mRNA in cerebral cortex was down-regulated immediately after anesthesia and at 1 and 7 days after anesthesia in group S (P＜0.05).Conclusion The mechanism underlying sevoflurane-induced cognitive impairment may be related to the down-regulated expression of ADRA1B and ADRA1D in cerebral cortex of rats.

Objective: To explore the efficacy of valvuloplasty on mitral valve regurgitation (MR) in infants and small children, in order to provide evidence for clinical treatment. Methods: Retrospective analysis was conducted in patients aged less than 3 years old who have undergone mitral repair surgeries at Department of Cardiovascular Surgery, General Hospital of Western Theater Command from January 2015 to December 2017.Cardiopulmonary bypass (CPB) surgery was performed under general anesthesia.The corresponding repair operations were selected for various MR types.All the children were examined by cardiac ultrasound before discharge.Patients were followed up after surgery and mitral regurgitation was recorded. Results: A total of 69 patients were enrolled, including 30 boys and 39 girls, with an average age of (19.3±11.6) months and an average weight of (9.6±2.1) kg.There were 32 cases of Carpentier type Ⅰ, 30 cases of type Ⅱ and 7 cases of type Ⅲ.Twenty-nine patients were diagnosed as simple MR, while the other 40 patients were combined with other cardiac malformations.One patient died at postoperative day 7.One patient still had severe MR after surgery, and then second operation was performed on the 10^th day after first surgery.Sixty-five patients were followed up from 1 month to 3 years[(15.9±10.9) months]. During the follow-up period, no patient died or had reoperation.Aggravated MR was observed in 4 patients. Conclusions Mitral valvuloplasty is a safe and effective surgical method for treating infants and younger children with MR.The key to the success of surgery is to choose the appropriate individualized repair operation.At the same time, the growth potential of mitral valve should be fully considered to avoid restrained development.

In recent years, the perioperative surgical home model has been gradually applied to the posterior spinal fusion for adolescent idiopathic scoliosis. This review summarizes the application of perioperative surgical home model in adolescent idiopathic scoliosis surgery, including the concept, connotation and elements, hoping to provide reference and reference for complex and high-risk surgical procedures.

Objective:To observe the optimal time interval of multiple short-term hyperthermia in tongue squamous carcinoma Cal-27 cells, and investigate the role of Notch signaling pathway in hyperthermia-induced apoptosis of Cal-27 cells.Methods:Cal-27 cells were placed into a 42℃ incubator for 45 min, and the second hyperthermia was performed at 6 h,12 h, 24 h, 48 h and 72 h later, respectively. Cell proliferation capacity was detected by CCK-8 assay at 0 h, 12 h and 24 h after the end of hyperthermia. After determining the optimal time interval of hyperthermia, multiple cycles of hyperthermia were performed, and the effects of hyperthermia on the proliferation and apoptosis of Cal-27 cells were detected by CCK-8 assay and flow cytometry, respectively. The changes in the expression of Notch1, Jagged1 and hairy and enhancer of split homolog-1 (Hes1) mRNA and proteins were analyzed by real-time reverse transcription PCR (qRT-PCR) and Western blot. All data were expressed as mean±SD. Two-group comparison was performed by one-way ANOVA.Results:Hyperthermia at 42℃ for 45 min every 12 h consistently inhibited the proliferation of Cal-27 cells ( P<0.05). Compared with the control group, hyperthermia in the experiment group significantly inhibited the proliferation and induced the apoptosis of Cal-27 cells after 7 cycles of hyperthermia ( P<0.05), and the expression levels of Notch1, Jagged1 and Hes1 mRNA and proteins in the hyperthermia group were significantly down-regulated (all P<0.05). Conclusions:The optimal time interval of hyperthermia to inhibit the proliferation of tongue squamous cells carcinoma Cal-27 cells is 12 h. Hyperthermia might induce the apoptosis of Cal-27 cells by inhibiting the Notch signaling pathway.

Objective:To explore the observation of the short-term recanalization rate and safety of acute thrombosis of arteriovenous fistula by dual-channel urokinase thrombolysis.Methods:A total of 52 dialysis patients with acute thrombosis of arteriovenous fistula in the Department of Nephrology, Shenzhen Hospital of Southern Medical University from January 2017 to January 2020 were selected. They were divided into control group and observation group by random number table. Twenty-seven cases in the test group used inflow arterial puncture and venous thrombosis, hereinafter referred to as dual channel, and bolus injection of urokinase for thrombolysis. Twenty-five cases in the control group were treated with tradi) ional peripheral intravenous bolus injection of urokinase for thrombolysis, and the recanalization time of internal fistula, adverse reactions and safety of thrombolysis were compared between the two groupsResults::The early (2 hours) reopening rate of the test group was 92.6% (25/27), which was higher than that of the control group by 44.0% (11/25) ( χ2 value was 14.389, P<0.05), which was statistically significant. The embolization site of the two groups of patients ( χ2 value was 2.989, P>0.05), the access situation of the two groups of patients ( χ2 value was 0.277, P>0.05), no statistical significance. There was no statistical significance in subcutaneous ecchymosis ( χ2 value was 0.088, P>0.05), bleeding at the puncture point ( χ2 value was 0.003, P>0.05), and puncture injury ( χ2 value was 0.944, P>0.05) in both groups. Conclusions:The double-channel urokinase thrombolysis method has the characteristics of high (2 hours) early recanalization rate, safe and effective in the treatment of acute arteriovenous fistula thrombosis.

Objective:To investigate the role and regulatory mechanism of triggering receptor expressed on myeloid cell 2 (TREM2) in mice lung ischemia/reperfusion injury (LIRI).Methods:Thirty-six healthy male C57BL/6 mice were divided into six groups according to the random number method ( n = 6): normal control group, and LIRI 2, 6, 12, 24, 48 hours group. Mice LIRI models were established by clamping the left hilum. The wet/dry weight ratio (W/D) of left lung tissue was measured. Lung injury was observed and evaluated by hematoxylin-eosin (HE) staining and electron microscopy. The levels of interleukins (IL-1β, IL-18) in lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of TREM2 and caspase-1 were determined by polymerase chain reaction (PCR). The protein expressions of TREM2, caspase-1, Gasdermin-D (GSDMD) were determined by Western blotting. Results:At 2 hours after LIRI, lung injury began to appear, the lung ultrastructure changed, and the lung injury score increased; at 6 hours, the degree of lung injury was the most serious; after 12 hours, the lung injury gradually reduced and the lung injury score gradually decreased. Compared with the normal control group, lung W/D ratio and lung injury score of LIRI 2, 6, 12, 24, 48 hours groups were significantly higher, the differences were statistically significant (lung W/D ratio: 7.06±0.52, 8.34±0.17, 6.42±0.35, 5.34±0.25, 5.59±0.45 vs. 4.69±0.23; lung injury score: 5.50±0.54, 9.75±0.89, 5.88±0.84, 3.63±0.74, 4.13±0.64 vs. 1.13±0.35, all P < 0.05). Compared with the normal control group, the levels of IL-1β and IL-18 in lung tissue were significantly increased at 2 hours after LIRI, reached a peak at 6 hours [IL-1β (ng/L): 502.76±12.25 vs. 56.50±8.07, IL-18 (ng/L): 414.02±10.75 vs. 81.63±5.29, both P < 0.05], then decreased gradually, and were still significantly higher than the normal control group at 48 hours. The PCR and Western blotting showed that the expression of TREM2 was significantly lower than that in the normal control group at 2 hours after LIRI, and reached a valley at 6 hours [TREM2 mRNA (2 -ΔΔCt): 0.47±0.05 vs. 1.02±0.05, TREM2/GAPDH: 0.23±0.13 vs. 0.48±0.17, both P < 0.05], then gradually increased, and reached the peak at 24 hours [TREM2 mRNA (2 -ΔΔCt): 3.98±0.15 vs. 1.02±0.05, TREM2/GAPDH: 0.71±0.17 vs. 0.48±0.17, both P < 0.05]. The trend of expression of caspase-1 and GSDMD were opposite to that of TREM2, which increased at first and then decreased, and reached a peak at 6 hours after reperfusion [caspase-1 mRNA (2 -ΔΔCt): 2.20±0.13 vs. 1.01±0.02, caspase-1/GAPDH: 0.64±0.02 vs. 0.20±0.06, GSDMD/GAPDH: 1.23±0.01 vs. 0.87±0.02, all P < 0.05]. Conclusions:TREM2 might be involved in LIRI in mice. The mechanism may be related to the effect of TREM2 on caspase-1-mediated pyroptosis.

OBJECTIVE: To compare the clinical application and health economic values of non-invasive prenatal testing (NIPT) and second trimester serum screening (STSS). METHODS: A retrospective analysis was carried out on 54 026 singleton pregnant women undergoing NIPT and STSS from March 1, 2018 to December 31, 2019 in Changsha Maternal and Child Health Care Hospital. For pregnant women with high-risk results of NIPT, prenatal diagnosis and follow-up of pregnancy outcomes were conducted. The data was grouped to 4 screening models, and their cost-benefit was analyzed. RESULTS: The sensitivity, specificity and positive predictive value of NIPT were all higher than STSS. Screening models 1 to 4 have prevented the birth of 71, 29, 52 and 54 patients with Down syndrome, respectively. The safety index of screening models 1 to 4 were 0.0036, 0.3944, 02215 and 0.1281, respectively. When the price of NIPT was decreased to 600 RMB, the cost-benefit of the screening models 1 to 4 was 0.46, 0.65, 0.44 and 0.40 million RMB, respectively. CONCLUSION NIPT has a better detection performance than STSS. When the price of NIPT is 600 RMB, screening model 1 has the best screening effect and the highest accuracy, safety index and health economical value.
Child ; China ; Cost-Benefit Analysis ; Down Syndrome/diagnosis* ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis/methods* ; Retrospective Studies

Acute leukemias caused by mixed lineage leukemia(MLL)gene rearrangements(MLL-r)are characterized by high invasiveness and a poor prognosis,with few specific treatment options available.MLL protein is essential in embryonic development and hematopoiesis.It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains,thus regulating downstream target gene expression through epigenetic modifications.MLL-r leads to the formation of MLL fusion proteins(MLL-FPs),in which the C-terminal is replaced by fusion partner proteins;over 100 such partner proteins have been identified to date.In numerous studies of the molecular mechanism,Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein,resulting in the disregulation of certain targeted genes,which makes the development of Menin-MLL inhibitors theoretically possible.To date,several small molecules have been identified that inhibit Menin-MLL interaction,including thienopyrimidine derivatives,piperidine derivatives,pyrimidine derivatives,and macrocyclic mimic peptides.Based on these prototypes,at least seven drugs are currently undergoing clinical evaluation,with some promising preliminary data regarding safety,tolerability,and efficacy.This review summarizes the structure and function of MLL,the mechanism of the occurrence of MLL-r leukemia,and current Menin-MLL inhibitors tested in MLL-r leukemia.

Objective:To analyze the changing trend of the incidence and mortality rates of liver cancer in the Chinese population from 1990 to 2019, and predict the future development trend of liver cancer.Methods:The descriptive epidemiologic method was conducted. Based on the Global Burden of Disease data from the Institute for Health Metrics and Evaluation at the University of Washington, the crude incidence rate and total number, crude mortality rate and total number, age- and sex-specific incidence rate and number, age- and sex-specific mortality rate and number of liver cancer in the Chinese population from 1990 to 2019 were collected. The age-standardized rate was calculated using the year 2000 China's standard population. Observation indicators: (1) the incidence and mortality of liver cancer in the Chinese population from 1990 to 2019; (2) changing trend of the age-standardized incidence and mortality rates of liver cancer in the Chinese population from 1990 to 2019; (3) prediction of the incidence and mortality of liver cancer in the Chinese population during 2020-2044. Count data were described as absolute numbers, percentages and ratios. The Joinpoint V.4.9.0.0 software was used to calculate the annual percent change (APC), average annual percent change (AAPC) and its 95% confidence interval ( CI) of age-standardized incidence and mortality rates of liver cancer in different time periods. The age-period-cohort model in the Nordpred package of R software (V.4.1.1) was used to predict the incidence and mortality of liver cancer in the Chinese population during 2020-2044. Results:(1) The incidence and mortality of liver cancer in the Chinese population from 1990 to 2019: the crude incidence rate and the age-standardized incidence rate of liver cancer in the Chinese population decreased from 20.01/100,000 and 24.31/100,000 in 1990 to 14.80/100,000 and 9.71/100,000 in 2019, respectively. The crude incidence rate and the age-standardized incidence rate of liver cancer in the Chinese male popula-tion decreased from 27.88/100,000 and 34.76/100,000 in 1990 to 22.05/100,000 and 15.22/100,000 in 2019, respectively. The crude incidence rate and the age-standardized incidence rate of liver cancer in the Chinese female population decreased from 11.63/100,000 and 13.51/100,000 in 1990 to 7.26/100,000 and 4.29/100,000 in 2019, respectively. The crude mortality rate and the age-standardized mortality rate of liver cancer in the Chinese population decreased from 19.64/100,000 and 23.97/100,000 in 1990 to 13.20/100,000 and 8.44/100,000 in 2019, respectively. The crude mortality rate and the age-standardized mortality rate of liver cancer in the Chinese male population decreased from 27.03/100,000 and 34.10/100,000 in 1990 to 19.18/100,000 and 13.03/100,000 in 2019, respectively. The crude mortality rate and the age-standardized mortality rate of liver cancer in the Chinese female population decreased from 11.78/100,000 and 13.64/100,000 in 1990 to 6.98/100,000 and 3.97/100,000 in 2019, respectively. (2) Changing trend of the age-standardized incidence and mortality rates of liver cancer in the Chinese population from 1990 to 2019: the trend of age-standardized incidence rate of liver cancer in the Chinese population could be divided into 5 periods, namely year 1990 to 1996, year 1996 to 2001, year 2001 to 2005, year 2005 to 2010 and year 2010 to 2019. In these 5 periods, the APC of age-standardized incidence rate changed from 1.27%(95% CI as 0.81% to 1.73%, P<0.001) to 1.12%(95% CI as 0.91% to 1.33%, P<0.001) of the total Chinese population, from 1.68%(95% CI as 1.19% to 2.17%, P<0.001) to 1.65%(95% CI as 1.42% to 1.87%, P<0.001) of the Chinese male population and from 0.21%(95% CI as -0.32 % to 0.75%, P=0.406) to -0.14%(95% CI as -0.40% to 0.11%, P=0.241) of the Chinese female population, respectively. The trend of age-standardized mortality rate of liver cancer in the Chinese population could be divided into 5 periods, namely year 1990 to 1996, year 1996 to 2000, year 2000 to 2005, year 2005 to 2012 and year 2012 to 2019. In these 5 periods, the APC of age-standardized mortality rate changed from 1.47%(95% CI as 0.74% to 2.20%, P=0.001) to 1.34%(95% CI as 0.78% to 1.90%, P<0.001) of the total Chinese population, from 1.96%(95% CI as 1.18% to 2.75%, P<0.001) to 1.79%(95% CI as 1.18% to 2.41%, P<0.001) of the Chinese male population and from 0.14%(95% CI as -0.54% to 0.82%, P=0.670 ) to 0.48%(95% CI as 0.02% to 0.93%, P=0.041) of the Chinese female population, respectively. From 1990 to 2019, the AAPC of age-standardized incidence and age-standardized mortality rates of liver cancer were -3.22%(95% CI as -3.41% to -3.03%) and -3.51%(95% CI as -3.82% to -3.19%) in the Chinese population, -2.90%(95% CI as -3.10% to -2.71%) and -3.22%(95% CI as -3.57% to -2.88%) in the Chinese male population, -3.96%(95% CI as -4.17% to -3.76%) and -4.13%(95% CI as -4.43% to -3.82%) in the Chinese female population, respectively. (3) Prediction of the incidence and mortality of liver cancer in the Chinese population during 2020-2044: the age-standardized incidence rate of liver cancer would decrease from 9.51/100,000 in 2015-2019 to 5.78/100,000 in 2040-2044 in the Chinese population, from 14.84/100,000 in 2015-2019 to 9.75/100,000 in 2040-2044 in the Chinese male population and from 4.28/100,000 in 2015-2019 to 1.88/100,000 in 2040-2044 in the Chinese female population, respectively. The age-standardized mortality rate of liver cancer would decrease from 8.40/100,000 in 2015-2019 to 4.62/100,000 in 2040-2044 in the Chinese population, from 12.91/100,000 in 2015-2019 to 7.59/100,000 in 2040-2044 in the Chinese male population and from 4.01/100,000 in 2015-2019 to 1.70/100,000 in 2040-2044 in the Chinese female population, respectively. The incidence number and mortality number of liver cancer from 2020 to 2044 would remain stable at around 160,000 per year and 140,000 per year in the Chinese population, 128,500 per year and 109,000 per year in the Chinese male population, 36,000 per year and 34,900 per year in the Chinese female population, respectively. Conclusion:The incidence and mortality rates of liver cancer in the Chinese popula-tion show a significant downward trend from 1990 to 2019, and the incidence number and mortality number of liver cancer in the Chinese population will remain stable above 100,000 during 2020-2044.