Objective To investigate the impact of serine/threonine-protein kinase 1(AKT1)-mediated autophagy in hepatocellular carcinoma(HCC)cells on their sensitivity to 125I seed irradiation.Methods ① iProX database and STRING12.0 website were utilized to analyze the proteomic data of HCC before and after 125I seed irradiation to explore the differentially expressed proteins and associated functional connections.Meanwhile,The Cancer Genomics Atlas(TCGA)database was employed to analyze the relationship between AKT1 expression level and the survival of HCC patients.② Human HCC cell lines HUH7 and Hep3B were exposed to continuous irradiation from 125I radioactive seeds with an initial apparent activity of 0.8 mCi per seed for approximately 120 h,accumulating a total dose of 8 Gy,while the control cells were cultured under normal condition for 120 h.③ Autophagy inhibitor,chloroquine(CQ)and inducer,rapamycin(RAPA)were used to treat the HCC cells respectively to establish the CQ group and the RAPA group.The lentiviral transfection technique was employed to construct the HCC cells with overexpressed AKT1,namely the AKT1 group.The HCC cells treated in the same way were continuously irradiated with 125I seeds for 120 h to construct the CQ+125I group,the RAPA+125I group,and the AKT1+125I group.④The changes in microtubule-associated protein light chain 3(LC3),p62,AKT1 and p-AKT1 were detected by Western blotting.Cell immunofluorescence assay was employed to observe the expression of autophagy related proteins,such as LC3.The colony forming ability and apoptotic rate were detected with plate cloning assay and flow cytometry.Results ① Continuous irradiation with 125I seeds resulted in decreased expression of p62 and increased ratio of LC3Ⅱ/LC3Ⅰ(P＜0.05)when compared with the negative control(NC)group.Immunofluorescence assay revealed more green fluorescence spots of LC3.When compared with the 125I group,the CQ+125I group had significantly increased expression of p62(P＜0.01),decreased ratio of LC3Ⅱ/LC3Ⅰ(P＜0.01),lower apoptotic rate(P＜0.01),and more colony formations(P＜0.01).In contrast,the results in the RAPA+125I group were opposite to those of the CQ+125I group.② Analysis on the iProX database showed that the expression of AKT1 was decreased in the irradiated group,and analysis on the TCGA database indicated that high expression of AKT1 predicted a poor prognosis for HCC patients(P＜0.01).③After irradiation with 125I seeds,the expression of AKT1 at both the RNA and protein levels was decreased in the 125I group(P＜0.01).After overexpression of AKT1,the level of autophagy was decreased(P＜0.05).Irradiation of HCC cells with overexpressed AKT1 using 125I seeds could partially restore the level of autophagy.In the AKT1+125I group,the expression of AKT1,pAKT1 and p62 were all decreased,and the ratio of LC3Ⅱ/LC3Ⅰwas increased than the AKT1 group(P＜0.05).④ The apoptotic rate of the AKT1+125I group was lower than that of the 125I group(P＜0.05)and higher than that in the AKT1 group(P＜0.05).In HUH7 cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group(P＜0.05).In Hep3B cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group,and the clonogenic ability of the AKT1 group was higher than that of the NC group(P＜0.05).Conclusion 125I seed irradiation induce lethal autophagy in HCC cells by reducing the expression of AKT1,providing a new theoretical basis for the implantation of 125I radioactive seeds in the treatment of HCC.

OBJECTIVE To study the effect and safety evaluation of percutaneous tracheotomy and traditional open tracheotomy in patients with severe pulmonary infection in ICU environment.METHODS A retrospective analysis was conducted on 80 patients with severe pulmonary infections admitted to the ICU of Shangqiu First People's Hospital from July 2019 to June 2022 as the subjects of the study.According to the tracheotomy approach,they were divided into the Percutaneous tracheotomy group(n=40)and the Conventional tracheotomy group(n=40).The Conventional tracheotomy group underwent traditional routine tracheotomy,while the Percutaneous tracheotomy group underwent percutaneous tracheotomy;all tracheotomies were performed by the same physician.The two groups were compared based on different tracheotomy techniques,and the surgical incision time,intraoperative blood loss,complete healing indicators were analyzed to evaluate the surgical outcomes and complication rates in each group.RESULTS Compared with the Conventional tracheotomy group,the Percutaneous tracheotomy group significantly reduced surgical time,intraoperative blood loss,and wound healing time after extubating(P<0.05),and the incidence of complications such as difficult cannulation,pneumothorax and subcutaneous emphysema decreased significantly,and the difference was statistically significant(P<0.05).In the BMI subgroup analysis of complications,it was found that in the BMI≥28.0 kg/m2 subgroup,the incidence of casing difficulty and pneumothorax complications in the Percutaneous tracheotomy group was lower than that in the Conventional tracheotomy group,and the difference was statistically significant(P<0.05).In the 22.0 kg/m2≤BMI<28.0 kg/m2 subgroup and BMI<22.0 kg/m2 subgroup,there was no significant difference in the difficulty of cannulation and pneumothorax complications between the two groups(P>0.05).CONCLUSION In ICU patients with severe pneumonia,early percutaneous tracheotomy can significantly reduce intraoperative bleeding blood volume,shorten the time of tracheotomy,especially in patients with BMI≥28.0 kg/m2,which has a lower incidence of complications.Percutaneous tracheotomy is worth promoting in ICU patients with severe lung infection who need tracheotomy.

Objective To investigate the role of a novel human-specific long noncoding RNA(lncRNA),MEK6-AS1,and its potential molecular mechanism in improving the osteogenic differentiation of senescent mesenchymal stem cells(MSCs).Methods An in vitro human MSCs replicative senescence model was established by sequen-tial passaging,and then senescence was identified by β staining and senescence-related gene expression.RT-qPCR was used to detect the expression of MEK6-AS1 during senescence and osteogenic differentiation of human MSCs(hMSCs);Lentiviral knockdown technology was used to regulate the expression of MEK6-AS1 in the MSCs replicative senescence model.Transcriptome sequencing technology was utilized to analyze the effects of MEK6-AS1 on the transcriptome of hMSCs especially on genes and pathways related to osteogenic differentiation.The effect of MEK6-AS1 as an intervention target at osteogenic differentiation of human senescent hMSCs was evaluated with alkaline phosphatase staining microscopy.PCR technology was used to detect osteogenic gene expression levels in cells.Results With aging process,the osteogenic differentiation ability of hMSCs decreased significantly while the expression level of MEK6-AS1 was enhanced(P＜0.000 1).Knockdown of MEK6-AS1 significantly enhanced the osteogenic differentiation of MSCs by the up-regulating expression of osteogenic markers and increasing minerali-zation capacity(P＜0.001).Conclusions Knockdown of human-specific lncRNA MEK6-AS1 improves osteogenic differentiation of senescent MSCs,providing a new target and theoretical basis for the treatment of senescence-asso-ciated osteoporosis.

Objective To investigate the relationships of the expression of serum long non-cod-ing RNA FGD5-AS1(lncRNA FGD5-AS1)and microRNA-133b(miR-133b)with clinicopathologi-cal features and prognosis in patients with colorectal cancer.Methods A total of 85 patients with colorectal cancer were selected and assigned to colorectal cancer group,and postoperative cancer tis-sues and adjacent tissues were obtained.Another 85 healthy individuals who underwent physical ex-aminations were selected as healthy group.The expression levels of lncRNA FGD5-AS1 and miR-133b in the serum of the two groups were compared,and the expression levels of lncRNA FGD5-AS1 and miR-133b in cancer tissues and adjacent tissues of patients were also compared.The correlation be-tween the expression levels of lncRNA FGD5-AS1 and miR-133b,as well as their relationships with the prognosis of colorectal cancer patients were analyzed.The influencing factors for the 3-year prog-nosis of patients were screened,and the predictive efficacy of lncRNA FGD5-AS1 and miR-133b for the prognosis of patients with colorectal cancer was evaluated.Results The expression level of ser-um lncRNA FGD5-AS1 in the colorectalcancer group was higher than that in the healthy group,while the expression level of miR-133b was lower than that in the healthy group(P＜0.05).In colorectal cancer tissues,the expression level of lncRNA FGD5-AS1 was higher than that in adjacent tissues,and the expression level of miR-133b was lower than that in adjacent tissues(P＜0.05).A negative correlation was observed between the expression of lncRNA FGD5-AS1 and miR-133b in the serum of patients with colorectal cancer(r=-0.402,P＜0.001).The expression levels of se-rum lncRNA FGD5-AS1 and miR-133b in patients were both associated with TNM stage,lymph node metastasis,and depth of tumor invasion(P＜0.05).The 3-year cumulative survival rate of patients with high expression of lncRNA FGD5-AS1 and low expression of miR-133b was lower than that of patients with low expression of lncRNA FGD5-AS1 and high expression of miR-133b,with a statistically significant difference(P＜0.05).LncRNA FGD5-AS1,miR-133b,TNM stage,and lymph node metastasis were all independent influencing factors for the 3-year prognosis of patients with colorectal cancer(P＜0.05).Receiver operating characteristic curve analysis showed that the area under the curve(AUC)for the combined prediction of the prognosis of patients with colorectal cancer by serum lncRNA FGD5-AS1 and miR-133b was 0.925,which was greater than the AUC for their individual predictions(P＜0.05).Conclusion High expression of serum lncRNA FGD5-AS1 and low expression of miR-133b are observed in patients with colorectal cancer.The expression lev-els of these two molecules are associated with clinicopathological features and poor prognosis,indica-ting their potential predictive value for the prognosis of patients.

Objective To comprehensively analyze the disease burden of respiratory cancers in China from 1990 to 2021, and predict the trend of disease burden changes from 2022 to 2031, in order to improve its prevention and treatment strategies. Methods Data from the Global Burden of Disease (GBD) 2021 database were extracted and analyzed for the disease burden of nasopharyngeal cancer, laryngeal cancer, and tracheal, bronchial and lung cancers (hereinafter referred to as lung cancer) in China from 1990 to 2021. The Joinpoint 4.9.1.0 software was utilized to analyze the corresponding trends. The grey prediction model [GM (1,1)] was employed to forecast the disease burden of respiratory cancers in China from 2022 to 2031. Results The disease burden of respiratory cancers attributed to tobacco and occupational carcinogens in China raised from 1990 to 2021. Among the respiratory cancers, lung cancer led in terms of incidence, mortality, and disability-adjusted life years (DALY) and their respective age-standardized rates from 1990 to 2021, followed by nasopharyngeal cancer, with laryngeal cancer being the lowest. Analysis via the Joinpoint regression model indicated that, overall, the disease burden of nasopharyngeal and laryngeal cancers in China decreased during this time period, while that of lung cancer increased. From a gender perspective, the disease burden of male patients was significantly higher than that of female patients from 1990 to 2021. Compared to the global average, the disease burden of respiratory cancers in China from 1990 to 2021 was still relatively heavy. As of 2021, the middle-aged and elderly population above 50 years old was the primary group suffering from the disease burden of respiratory cancers in China. The prediction model showed that the age-standardized rate of nasopharyngeal cancer in China would decline from 2022 to 2031; the age-standardized incidence rate of laryngeal cancer in China would increase, while its age-standardized mortality rate and DALY rate would both decrease; the age-standardized rates of lung cancer in China would increase. Conclusion In the past 30 years, the disease burden of nasopharyngeal and laryngeal cancers in China has lightened, but the overall disease burden of lung cancer is still on the rise. Compared to the global average, the disease burden of respiratory cancers in China is still relatively heavy. The disease burden in male patients is significantly higher than that in female patients, and the population above 50 years old is the main group suffering from the disease burden. In the next 10 years, the disease burden of respiratory cancers in China will still tend to increase. Therefore, targeted prevention and treatment strategies for men and the middle-aged and elderly populations remain key challenges that urgently need to be addressed in China's response to respiratory cancers.

Objective The aim of this study was to evaluate the efficacy and side effects of sacubitril/valsartan in the treatment of patients with chronic kidney disease(CKD)at stage 5 with resistant hypertension,and to explore the cardiovascular benefits and security of medical in the patients.Methods Patients with CKD5 resistant hypertension diagnosed and treated in the First Affiliated Hospital of Guangxi Medical University from September 2020 to March 2022 were selected and divided into the observation group(treated with routine treatment of kidney disease at end-stage and sacubitril/valsartan)and control group(include droutine treatment of renal disease at end-stage and ACEI or ARB drugs)according to treatment strategy.The patients in both two groups were treated with adequate dialysis treatment and conventional drug treatment of renal disease at end-stage.The patients were followed up for at least 3 months,the clinical efficacy of three months after treated with sacubitril/valsartan was observed,and the efficacy indicators and security indicators and adverse cardiovascular events were observed,the occurrence of adverse effects during the period of drug use were compared with the control group.Results A total of 110 patients were included in this study and there were 55 cases in each group.There were no significant differences in gender,age,age of dialysis,etiology,dialysis mode and blood pressure between the two groups(P>0.05).The Systolic blood pressure(SBP),diastolic blood pressure(DBP),b-type urinary natriuretic peptide precursor(Pro-BNP)and cardiac function grade in the observation group after treatment was significantly decreased compared with before treatment.The left ventricular ejection fraction(LVEF)and the ratio of LVEF<50%in the observation group was significantly reduced after treatment(P<0.05).SBP,DBP and Pro-BNP decreased 3 months after treatment compared with the baseline before treatment,and improved significantly in the first month after treatment(P<0.05).The decrease of DBP and BNP before and after treatment was significantly different between the two groups,and the decrease of DBP and BNP was more significant in the observation group(P<0.05).The difference of LVEF and left ventricular end diastolic diameter(LVEDD)between the two groups before and after treatment was statistically significant,and the improvement was more obvious in the observation group(P<0.05).There were no significant differences in the safety indicators of serum potassium,estimated glomerular filtration rate(eGFR)and liver function between two groups before and after treatment(P>0.05).In terms of adverse reactions,only 1 case in the control group developed hyperkalemia within 3 months of follow-up,and no hypotension or other adverse reactions occurred in the two groups.Conclusions The treatment of patients with CKD stage 5 hypertension with sacubitril/valsartan has obvious cardiovascular benefits.Sacubitril/Valsartan has efficacy in lowering blood pressure,improving cardiac function and reducing volume load,with less adverse events and higher safety than control group.

OBJECTIVE To analyze the compositional differences between Fructus Tritici Levis and Triticum aestivum， and to provide reference for identification and quality control of both. METHODS Twenty batches of Fructus Tritici Levis and three batches of T. aestivum were collected， and their fingerprints were acquired by high-performance liquid chromatography and the similarities were evaluated by the Evaluation System of Similarity of Chromatographic Fingerprints of Traditional Chinese Medicine （2012 version）. Cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed to analyze the difference of Fructus Tritici Levis and T. aestivum from different regions， and the differential components were screened. The contents of the six identified components in Fructus Tritici Levis and T. aestivum were determined. RESULTS The similarities of the fingerprints of Fructus Tritici Levis ranged from 0.928 to 0.996， and the relative similarities of T. aestivum with Fructus Tritici Levis ranged from 0.761 to 0.773. A total of 19 common peaks were calibrated， and six components including linolenic acid， linoleic acid， 5-heptadecylresorcinol， 5-nonadodecylresorcinol， 5- heneicosylresorcinol， and 5-tricosylresorcinol were identified. The results of CA and PCA showed that Fructus Tritici Levis and T. aestivum could be clearly distinguished； the distribution of Fructus Tritici Levis from Anhui province was relatively concentrated. The results of OPLS-DA showed that linolenic acid， linoleic acid， and other six unknown compounds were the differential components between Fructus Tritici Levis and T. aestivum. The average contents of the six identified components in Fructus Tritici Levis were 0.100 9， 1.094 0， 0.005 1， 0.030 9， 0.098 2，and 0.024 8 mg/g， respectively； the contents of linolenic acid and linoleic acid in Fructus Tritici Levis were significantly higher than those in T. aestivum （P＜0.05）.CONCLUSIONS The established qualitative and quantitative methods are simple and reliable， and can be used for the identification and quality evaluation of Fructus Tritici Levis and T. aestivum. The identified differential components， such as linolenic acid and linoleic acid， can also provide clues for the differentiation and pharmacological study of Fructus Tritici Levis and T. aestivum.

OBJECTIVE To analyze the compositional differences between Fructus Tritici Levis and Triticum aestivum， and to provide reference for identification and quality control of both. METHODS Twenty batches of Fructus Tritici Levis and three batches of T. aestivum were collected， and their fingerprints were acquired by high-performance liquid chromatography and the similarities were evaluated by the Evaluation System of Similarity of Chromatographic Fingerprints of Traditional Chinese Medicine （2012 version）. Cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed to analyze the difference of Fructus Tritici Levis and T. aestivum from different regions， and the differential components were screened. The contents of the six identified components in Fructus Tritici Levis and T. aestivum were determined. RESULTS The similarities of the fingerprints of Fructus Tritici Levis ranged from 0.928 to 0.996， and the relative similarities of T. aestivum with Fructus Tritici Levis ranged from 0.761 to 0.773. A total of 19 common peaks were calibrated， and six components including linolenic acid， linoleic acid， 5-heptadecylresorcinol， 5-nonadodecylresorcinol， 5- heneicosylresorcinol， and 5-tricosylresorcinol were identified. The results of CA and PCA showed that Fructus Tritici Levis and T. aestivum could be clearly distinguished； the distribution of Fructus Tritici Levis from Anhui province was relatively concentrated. The results of OPLS-DA showed that linolenic acid， linoleic acid， and other six unknown compounds were the differential components between Fructus Tritici Levis and T. aestivum. The average contents of the six identified components in Fructus Tritici Levis were 0.100 9， 1.094 0， 0.005 1， 0.030 9， 0.098 2，and 0.024 8 mg/g， respectively； the contents of linolenic acid and linoleic acid in Fructus Tritici Levis were significantly higher than those in T. aestivum （P＜0.05）.CONCLUSIONS The established qualitative and quantitative methods are simple and reliable， and can be used for the identification and quality evaluation of Fructus Tritici Levis and T. aestivum. The identified differential components， such as linolenic acid and linoleic acid， can also provide clues for the differentiation and pharmacological study of Fructus Tritici Levis and T. aestivum.

Objective:To investigate the incidence characteristics and influencing factors of non-alcoholic fatty liver disease (NAFLD) in rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps and to provide scientific evidence for early identification and prevention of NAFLD for residents.Methods:A total of 10 158 participants were included from the Xinjiang Uygur ethnic group population cohort. A prospective cohort study and Cox proportional hazards regression model analysis were used to explore the influencing factors and clustering of NAFLD, and the dose-response relationship between related biochemical indicators and the risk of NAFLD was studied using a restricted cubic spline.Results:The cumulative incidence rate of NAFLD was 6.9%, and the incidence density of NAFLD was 12.06/1 000 person-years. The incidence density of NAFLD in females was higher than in males (14.72/1 000 person-years vs. 9.17/1 000 person-years, P<0.001). The incidence density of NAFLD gradually increased with age in the total population, both men and women (all P<0.001). In the general population, an education level of junior high school or above was a protective factor for NAFLD, while older age, divorce, widowhood, overweight, obesity, hypertension, increased glomerular filtration rate, decreased HDL-C, increased LDL-C, and increased ALT were risk factors for NAFLD. Estimated glomerular filtration rate (eGFR), HDL-C, LDL-C, and ALT were non-linearly correlated with the incidence of NAFLD, and there was a significant dose-response relationship between them. Only 19.1% of residents had no NAFLD risk factors; over 80.9% had ≥1 NAFLD risk factors. The risk of NAFLD increased with the number of risk factors. Conclusions:The incidence of NAFLD in rural Uygur ethnic group residents in Xinjiang Production and Construction Corps was relatively low, but most residents had one or more risk factors for NAFLD. Prevention and control of NAFLD in this population cannot be ignored. In addition, people of older age, divorced or widowed, low education level, overweight or obese, hypertension, and abnormal eGFR, HDL-C, LDL-C, and ALT were the high-risk groups of NAFLD that need to be paid attention to in this population.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.