Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE To explore the effects and potential mechanism of plumbagin on the inflammatory response and oxidative stress in rats with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） based on Notch1/GATA3 signaling pathway. METHODS Ten rats were randomly selected as the control group； another 65 rats were used to establish the AECOPD model by inhaling cigarette smoke， intratracheal administration of endotoxin， and nasal inoculation of bacteria. The 50 successfully modeled rats were randomly divided into the AECOPD group， plumbagin low-dose group （10 mg/kg）， plumbagin high-dose group （50 mg/kg）， positive control group （dexamethasone 0.09 mg/kg）， and high-dose plumbagin+Jagged1 （Notch1 activator） group （50 mg/kg+25 mg/kg）， with 10 rats in each group. Each group was administrated intragastrically or intraperitoneally with the corresponding drug solution or normal saline， once a day for 28 consecutive days. After the last administration， the lung function indicators （peak expiratory flow， the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity）， the number of inflammatory cells （white blood cells， lymphocytes， neutrophils， macrophages） in bronchoalveolar lavage fluid， the levels of inflammatory factors [interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）] in lung tissue， and the contents of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in lung tissue were all determined in each group； the pathological changes of lung tissue and the pathological scores， as well as protein expressions of mucin 5ac （Muc5ac）， Notch1 and GATA3 in lung tissue were also detected. RESULTS Compared with the control group， the lung tissue of the AECOPD group rats showed severe damage to the alveolar wall structure， with a large number of inflammatory cells infiltration and accompanied by pathological changes such as thickening of the airway wall； their lung function indicators， IL-10 level， and SOD content were significantly decreased； while the number of various inflammatory cells， IL-6 and TNF-α levels， MDA content， pathological score， as well as protein expressions of Muc5ac， Notch1 and GATA3 were significantly increased or upregulated （P＜0.05）. Compared with the AECOPD group， the pathological changes in the lung tissue of the rats in each plumbagin dose group were significantly alleviated， and the above quantitative indicators were significantly improved， and the improvement was more obvious in the plumbagin high- dose group （P＜0.05）. Jagged1 significantly reversed the protective effect of high-dose plumbagin on lung injury and related indicators in AECOPD rats （P＜0.05）. CONCLUSIONS Plumbagin can inhibit the inflammatory response and oxidative stress in the lungs of AECOPD rats， alleviate lung damage， and improve lung function. The above effects may be related to the inhibition of the Notch1/GATA3 signaling pathway.

Purpose To investigate the effect of MYD88 gene overexpression on the proliferation and apoptosis of human diffuse large B cell lymphoma(DLBCL)cells,and to prelimi-narily explore the mechanism of MYD88 gene action.Methods PEGFP-C2-MYD88 overexpressing MYD88 L265P gene was transfected into DLBCL cells by plasmid transfection.The exper-iment was divided into blank control group,negative control group and MYD88 L265P overexpression group.The fluores-cence expression of MYD88 L265P after overexpression was ob-served under inverted fluorescence microscope.RT-PCR and Western blot were used to detect the mRNA and protein expres-sion of MYD88 L265P,IRAK4,NF-κB and BCL2 in DLBCL cells before and after overexpression of MYD88 L265.CCK8 method was used to detect DLBCL cells proliferation and Ho-echst staining was used to detect DLBCL cells apoptosis.Re-sults After overexpression of MYD88 L265P,compared with the blank control group(0.670 4±0.017 5)and the negative control group(0.715 3±0.019 6),the MYD88L265P overex-pression group(1.157 2±0.010 2)increased significantly,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(0.69 ±0.04)and the negative control group(0.81±0.07),the MYD88L265P overexpression group(0.48±0.05)was signifi-cantly decreased,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(mRNA:1.0158±0.0115,0.987 3±0.010 2,1.007 6±0.015 3,protein:0.183 4±0.058 9,0.096 8± 0.015 7,0.147 5±0.0418)and negative control group(mR-NA:0.9132±0.0098,1.0032±0.0156,0.9327± 0.011 2,protein:0.187 9±0.042 3,0.088 9±0.0513,0.134 8±0.050 1),the mRNA(3.243 2±0.013 6,2.976 6 ±0.0213,1.585 9±0.019 8)and protein expressions(0.452 7±0.052 4,0.218 9±0.047 5,0.301 4±0.059 8)of IRAK4,NF-κB and anti-apoptosis protein BCL2 in MYD88L265P overexpression group were significantly increased,which was statistically significant(all P＜0.05).Conclusion After overexpression of MYD88 L265P,the apoptosis rate of DLBCL cells decreased and the cell proliferation rate increased.The mechanism may be related to the mutation of MYD88 L265P gene,activation and amplification of NF-κB pathway,and pro-motion of the overexpression of antiapoptotic protein BCL2.

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

In recent years, increasing evidence has shown that hyperthermia is safe, effective and causes low toxicity. Hyperthermia can exert synergistic effect with other treatments, such as radiotherapy and chemotherapy. It has become an important adjuvant anti-tumor treatment secondary to surgery, chemotherapy, radiotherapy and biological treatment. Hyperthermia can improve the efficacy of radiotherapy and chemotherapy by directly inhibiting tumor cells and heat-induced radiosensitizing effect. Hence, hyperthermia is gradually applied in the multimodality treatment of tumors. In this article, we intend to review the research progress on the application of tumor hyperthermia in conventional radiotherapy, chemotherapy, immunotherapy and new biomaterials.

Objective: To synthesize and analyze ¹⁸F-prostate specific membrane antigen (PSMA)-1007, followed by its imaging in prostate cancer. Methods: Based on one-step method, ¹⁸F-PSMA-1007 was produced by the CFN-MPS-200 automatic synthesis module and its quality analysis was conducted. ¹⁸F-PSMA-1007 PET/CT imaging was performed in a prostate cancer patient (66 years old). Results: The synthesis time of ¹⁸F-PSMA-1007 was about 50 min, and the radiochemical yield was (25.0±5.0) % (attenuation correction, n=3). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (410.0±11.0) MBq/ml and the radioactive nuclear purity was above 99.0%. PET/CT imaging in the patient showed that ¹⁸F-PSMA-1007 was highly concentrated in prostate cancer with maximum standardized uptake value (SUV_max) of 40.9. Conclusion Based on CFN-MPS-200 multifunction synthesis module, ¹⁸F-PSMA-1007 can be stably synthesized with high radiochemical yield and can be concentrated in prostate cancer.

Radiotherapy is a critical approach for the comprehensive treatment of non-small cell lung cancer.Deep understanding of the individualized radiosensitivity of lung cancer patients plays a pivotal role in the selection of radiotherapy dosage and regime and establishment of comprehensive therapeutic strategies.Currently,multiple researchers have identified a variety of biomarkers in predicting the radiosensitivity of lung cancer patients.In this article,research progress on the biomarkers in predicting radiosensitivity of non-small cell lung cancer was reviewed.

Objective To investigate the clinical efficacy of atorvastatin combined with trimetazidine in the treatment of coronary heart disease .Methods 80 patients with coronary heart disease were selected as the research subjects.80 patients were randomly divided into two groups .The observation group was given atorvastatin combined with trimetazidine .The control group was treated with trimetazidine .The clinical efficacy ,serum lipids levels ,hemody-namic changes and adverse reaction were observed and evaluated .Results The observation group had markedly effective in 31 cases,effective in 7 cases,ineffective in all cases ,the total effective rate was 95.0％,which was signifi-cantly higher than 77.5％of the control group(effective in 10 cases,ineffective in 9 cases,χ2 =6.818,P<0.05). The levels of TG,TC,LDL-C,HDL-C in the observation group were (1.2 ±0.2) mmol/L,(2.4 ±1.0) mmol/L, (1.5 ±0.0) mmol/L,(0.7 ±0.1) mmol/L,which in the control group were (1.6 ±0.1) mmol/L,(3.59 ± 1.2)mmol/L,(2.2 ±0.1)mmol/L,(0.9 ±0.2)mmol/L,the serum lipids levels between the two groups had statisti-cally significant differences (t =5.41,3.47,4.87,2.05,P<0.05).The whole blood viscosity (low cut),blood viscosity(high cut),plasma viscosity of the observation group were (6.98 ±0.23)mPa· s,(5.07 ±0.13)mPa· s, (1.21 ±0.12) mPa· s,which were significantly lower than those of the control group [(9.01 ±0.21) mPa· s, (6.01 ±0.01)mPa· s,(1.54 ±0.21)mPa· s,t=5.24,4.47,5.44,all P<0.05].In the observation group,0 case of dizziness,1 case of skin rash,nausea and vomiting in 1 case,the incidence rate of adverse reactions was 5.0％.In the control group,2 cases of dizziness,3 cases of skin rash,nausea and vomiting in 4 cases,the incidence rate of adverse reaction was 22.5％,there was no statistically significant difference between the two groups (χ2 =0.867,P>0.05).Conclusion The clinical curative effect of atorvastatin combined with trimetazidine in the treatment of coro -nary heart disease is accurate ,it can reduce blood fat,improve the abnormal blood rheology ,and it is safe,with less adverse reactions ,which is worthy of application and promotion .