Analysis of fertility intention to have a third child among childbearing age women in Wanzhou District of Chongqing Municipality and its influencing factors / 重庆医学

Objective To survey the current situation of fertility intention to have a third child among childbearing age women in Wanzhou District of Chongqing Municipality under the background of the new fer-tility policy,and to analyze its influencing factors.Methods The convenience sampling method was adopted to conduct the survey on the third child fertility intention by the self-designed questionnaire and the Question-naire Star platform among the childbearing women with one child or two children in Wanzhou District of Chongqing Municipality from September to October 2022.The multiple linear regression analysis and two-step cluster analysis were used to explore the influencing factors.Results A total of 632 questionnaires were re-ceived,32 invalid questionnaires were excluded,and the effective recovery rate was 94.9％.The score of fertili-ty intention to have a third child in the respondents was(12.81±2.83)points.The multiple linear regression analysis showed that the age,marital status,place of residence,spouse cultural degree,family rearing child model,whether the family can provide support and previous vaginal delivery history were the influencing fac-tors of fertility intention to have a third child among the childbearing age women in this place(P＜0.05).The two step cluster analysis showed that"obstetrician/midwife's help"was the most important predictive factor for the childbearing age women to choose to have a third child.Conclusion The current situation of childbear-ing age women's fertility intention to have a third child in Wanzhou District of Chongqing Municipality is not optimistic.It is necessary to create the positive factors that encourage childbearing age women to make deci-sion about having a third child.

Construction and validation of a model for predicting the risk of in-hospital cardiac arrest in emergency rooms / 中华急诊医学杂志

Objective:The predictive model of cardiac arrest in the emergency room was constructed and validated based on Logistic regression.Methods:This study was a retrospective cohort study. Patients admitted to the emergency room of the First Affiliated Hospital of Xinjiang Medical University from January 2020 to July 2021 were included. The general information, vital signs, clinical symptoms, and laboratory examination results of the patients were collected, and the outcome was cardiac arrest within 24 hours. The patients were randomly divided into modeling and validation group at a ratio of 7:3. LASSO regression and multivariable logistic regression were used to select predictive factors and construct a prediction model for cardiac arrest in the emergency room. The value of the prediction model was evaluated using the area under the receiver operator characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).Results:A total of 784 emergency room patients were included in the study, 384 patients occurred cardiac arrest. The 10 variables were ultimately selected to construct a risk prediction model for cardiac arrest: Logit( P)= -4.503+2.159×modified early warning score (MEWS score)+2.095×chest pain+1.670×abdominal pain+ 2.021×hematemesis+2.015×cold extremities+5.521×endotracheal intubation+0.388×venous blood lactate-0.100×albumin+0.768×K ++0.001×D-dimer. The AUC of the model group was 0.984 (95% CI: 0.976-0.993) and that of the validation group was 0.972 (95% CI: 0.951-0.993). This prediction model demonstrates good calibration, discrimination, and clinical applicability. Conclusions:Based on the MEWS score, chest pain, abdominal pain, hematemesis, cold extremities, tracheal intubation, venous blood lactate, albumin, K +, and D-dimer, a predictive model for cardiac arrest in the in-hospital emergency room was constructed to predict the probability of cardiac arrest in emergency room patients and adjust the treatment strategy in time.

Association between the ratio of dietary vitamin A to body weight and hypertension in children / 中国学校卫生

Objective@#To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention.@*Methods@#Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension.@*Results@#The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01].@*Conclusions@#The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Genetic and phenotypic analysis of MYO15A rare variants associated with autosomal recessive hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.

Application and reflection on smart Party building management platform under the new situations / 现代医院

To date,the information technology develops rapidly and the dawn of digital era comes just around the cor-ner.Under these new situations,smart Party building management platforms stand as a new impetus,energizing the Party build-ing efforts with robust capabilities for data storage,analysis,automatic computation,and administration.These platforms provide comprehensive data support that enhances the precision and efficiency of Party building.This leads to an invigorated process of continuous innovation and high-quality development within the Party building.This article delves into the practical application of the current unit's smart party building management platform,examining the challenges encountered during its operation.It also posits several reflections and strategic responses aimed at elevating the scientific management standards of party building.

Analysis of retinal and choroidal blood flow density in the macular areas of both eyes of children with mild monocular myopia / 中国医科大学学报

Objective To assess retinal and choroidal blood flow density in the macular regions of children diagnosed with unilateral low myopia using optical coherence tomography angiography(OCTA).This study aimed to investigate the clinical significance of these mea-surements.Methods A cross-sectional study was conducted on 90 eyes of 45 children with monocular myopia and adolescents aged 8 to 14 years who visited the outpatient department of the Ophthalmology of Dalian Third People's Hospital between June 2022 and February 2023.Optometry was performed after a 1%cyclopentolate cycloplegic muscle paralysis.Eyes with spherical equivalent(SE)-3.00 D to-0.50 D were included in the myopia group,whereas those with SE-0.25 D to＜+2.00 D were placed in the non-myopia group.The Master system was used to measure axial length(AL)and corneal curvature radius(CR),and to calculate AL/CR.Heidelberg spectral-domain optical coherence tomography(SD-OCT)was used to perform horizontal linear scanning of the macular area to obtain subfoveal choroidal thickness(SFCT).The OCTA module was used to obtain 3 mm×3 mm choroidal blood flow images,which were imported into ImageJ graphics processing software to obtain the blood flow densities of the superficial choroidal plexus(SCP),deep choroidal plexus(DCP),choroidal capillary(CC),and foveal avascular zone(FAZ).Pearson's correlation was used to examine the correlations between each blood flow parameter and age,AL,CR,AL/CR,and SFCT.Results The SE and SFCT of the myopia group were smaller(P＜0.05)than those of the non-myopia group,whereas the AL and AL/CR were significantly larger(P＜0.05)than those of the non-myopia group.The DCP blood flow density in the myopia group was significantly lower than that in the non-myopia group(P＜0.01).There was no statistically sig-nificant difference between the residual blood flow parameters of the myopia and non-myopia groups(P＞0.05).The Pearson's correlation analysis indicated that the SCP and DCP blood flow densities in the myopia group were positively correlated with SE(r= 0.611,0.731,P＜0.05),negatively correlated with AL(r=-0.568,-0.712,P＜0.05),and negatively correlated with AL/CR(r=-0.557,-0.564,P＜0.05).The SCP and DCP blood flow densities were negatively correlated with AL/CR in the non-myopia group(r=-0.615,-0.656,P＜0.05).The CC density and FAZ area in the two groups did not correlate with age,SE,AL,CR,AL/CR,or SFCT(P＞0.05).Conclusion Com-pared to non-myopic eyes,the eyes of children with mild monocular myopia had lower DCP blood flow density.Moreover,retinal blood flow density in myopic eyes was correlated with SE,AL,and AL/CR,whereas retinal blood flow density in non-myopic eyes was only correlated with AL/CR.

Research on the value of double closed-loop management mode in maintenance and fault control of hemodialysis machine / 中国医学装备

Objective:To construct a double-closed-loop management model for medical equipment and explore its application value in hemodialysis machine maintenance and fault management.Methods:Based on the closed-loop management of clinical operation of medical equipment and the closed-loop management of technical support,a dual closed-loop management model of equipment was constructed.65 hemodialysis machines in clinical use in Huashan Hospital Fudan University from January 2021 to January 2023 were selected and divided into a conventional mode and double-closed-loop mode according to different management modes.The conventional mode adopted conventional equipment management methods,and the double-closed-loop mode adopted a double-closed-loop management model.The cost-effectiveness,social benefit,failure occurrence,effective management quality matters,disinfection status,average patient waiting time and satisfaction were compared between the two groups.Results:The hemodialysis machine operating profit growth rate,diagnosis and treatment cost growth rate,service life index,scientific research service growth rate,diagnosis and treatment service growth rate,startup rate and operation rate of the double-closed-loop mode were(3.95±1.04)%,(3.80±0.58)%,(1.58±0.31)%,(4.30±0.95)%,(7.91±1.58)%,(96.58±2.76)%and(89.90±5.58)%,which were higher than those of the Conventional mode,the difference was statistically significant(t=5.418,10.070,7.490,17.570,11.820,8.849,6.840,P<0.05).The technical support expenses growth rate,bacterial colony count,bacterial endotoxin content and average patient waiting time of patients in the Double-closed-loop mode were(2.60±0.33)%,(0.370±0.008)cfu/ml,(0.0063±0.0011)EU/ml and(0.76±0.13)h,which were less than those of the conventional mode,the difference was statistically significant(t=23.040,82.985,14.482,19.530,P<0.05).The incidence rate of hemodialysis machine failure in the double-closed-loop mode was 9.23%(6/65),which was lower than that in the conventional mode,the difference was statistically significant(x2=6.392,P<0.05);among the 120 items of management data collected,quality control testing,maintenance and repair,clinical operation,information data,and scrap processing effectiveness rates were 95.83%(115/120),89.17%(107/120),96.67%(116/120),95.00%(114/120),and 97.50%(117/120),respectively,which were higher than those of the conventional mode,the difference was statistically significant(x2=15.238,16.596,9.808,15.585,16.119,P<0.05).Conclusion:The application of closed-loop management model to hemodialysis machine maintenance and fault management can effectively improve equipment cost-effectiveness,social benefits,management quality and patient satisfaction,and reduce the incidence of faults.

Application Study of Enzyme Inhibitors and Their Conformational Optimization in The Treatment of Alzheimer’s Disease / 生物化学与生物物理进展

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

The Functional Role of SUMOylation in The Tumor Microenvironment / 生物化学与生物物理进展

Tumors continue to be a major challenge in human survival that we have yet to overcome. Despite the variety of treatment options available, we have not yet found an effective method. As more and more research is conducted, attention has been turned to a new field for tumor treatment—the tumor microenvironment (TME). This is a dynamic and complex environment consisting of various matrix cells surrounding cancer cells, including surrounding immune cells, blood vessels, extracellular matrix, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules, and some specific cell types. Firstly, endothelial cells play a key role in tumor development and the immune system’s protection of tumor cells. Secondly, immune cells, such as macrophages, Treg cells, Th17 cells, are widely involved in various immune responses and activities in the human body, such as inflammation responses promoting survival carefully orchestrated by the tumor. Even though many studies have extensively researched the TME and found many research schemes, so far, no key effective method has been found to treat tumors by affecting the TME. The TME is a key interaction area between the host immune system and the tumor. Cells within the TME influence each other and interact with cancer cells to affect cancer cell invasion, tumor growth, and metastasis. This is a new direction for cancer treatment. In the complex environment of the TME, post-translational modifications (PTMs) of proteins have been proven to play an important role in the TME. PTMs are dynamic, strictly regulated changes to proteins that control their function by regulating their structure, spatial location, and interaction. Among PTMs, a reversible post-translational modification called SUMOylation is a common regulatory mechanism in cellular processes. It is a post-translational modification that targets lysine residues with a small ubiquitin-like modifier (SUMO) in a reversible post-translational modification manner. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis, and apoptosis, playing a pivotal role in the TME, such as DNA damage repair, tumor metastasis, and also participates in immune cell differentiation, activation, and inhibition of immune cells. On the other hand, SUMO or sentrin-specific protease (SENP) inhibitors can interfere with the SUMOylation process, thereby affecting many biological processes, including immune response, carcinogenesis, cell cycle progression, and cell apoptosis, etc. In summary, this review aims to introduce the dynamic modification of protein SUMOylation on various immune cells and the application of various inhibitors, thereby exploring its role in the TME. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs. In conclusion, the TME is a complex and dynamic environment that plays a crucial role in the development and progression of tumors. Understanding the intricate interactions within the TME and the role of PTMs, particularly SUMOylation, could provide valuable insights into the mechanisms of tumor development and potentially lead to the development of novel therapeutic strategies. The study of SUMOylation and its effects on various immune cells in the TME is an exciting and promising area of research that could significantly advance our understanding of tumor biology and potentially lead to the development of more effective treatments for cancer. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs.

Binding and carrying role of human serum albumin from various sources to sphingosine-1-phosphate / 中国输血杂志

【Objective】 To investigate the binding and carrying effects of human serum albumin (HSA) from various sources on sphingosine-1-phosphate (S1P). 【Methods】 Utilizing human plasma-derived HSA (pHSA) and recombinant HSA (rHSA) samples as the focal points of our investigation, LC-MS/MS technology was employed to meticulously compare and analyze the disparities in S1P content among the aforementioned samples. Subsequently, under physiological concentration conditions, S1P was directly introduced to HSA samples for loading processing, facilitating a comprehensive comparison of the binding efficacy of HSA from different sources to S1P. Within a serum-free culture setting, HSA samples from various sources were co-cultured with HUVEC cells. The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed, allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was calculated using surface plasmon resonance (SPR) technology. Furthermore, leveraging AutoDock Vina software and the Molprophet platform, the molecular docking analysis of HSA and S1P was conducted, aiming to predict the key binding pocket domain of S1P within HSA. 【Results】 All pHSA samples exhibited detectable levels of S1P (ranging from 3.31±0.03 to 30.35±0.07 μg/L), with significant variations observed among pHSA samples from different manufacturers (P<0.001). Conversely, S1P was undetectable in all rHSA samples. Upon load treatment, the binding affinity of HSA from diverse sources to S1P demonstrated significant discrepancies (P<0.001), with rHSA exhibiting approximately double the average S1P loading compared to pHSA (ΔCrHSA=801.75±142.45 μg/L vs ΔCpHSA=461.94±85.73 μg/L; P<0.001, t=5.006). Co-culture treatment outcomes revealed a significant elevation in S1P concentration within the supernatant after 6 hours of co-culture across all HSA sample processing groups with HUVEC cells, while no changes were observed in the supernatant of the blank control group. Notably, significant differences in supernatant S1P concentration were observed among treatment groups at 6 h, 12 h, and 24 h (P<0.001). SPR analysis unveiled a stronger affinity of pHSA for S1P compared to rHSA (KDpHSA-S1P: 2.38E-06, KDrHSA-S1P: 3.72E-06). Molecular docking analysis and binding pocket prediction suggested that the key binding pocket of HSA and S1P may reside in the IB subdomain of the HSA molecule. 【Conclusion】 HSA from various sources exhibits distinct binding and carrying effects on S1P, which appear to be closely associated with the IB subdomain of the HSA molecule.

Effects of PATL1 on the proliferation and migration of gastric cancer cells and its mechanism of action / 安徽医科大学学报

Objective @#Objective @*Methods @#The expression levels of PATL1 in pancar- cinoma，gastric cancer and normal tissues were analyzed by TCGA database．The expression level of PATL1 in 40 human gastric cancer tissues and paired adjacent tissues was evaluated by quantitative real-time PCR (RT-qPCR) . The Kaplan-Meier Plotter database was used to analyze the prognosis of PATL1 in gastric cancer patients．The gas- tric cancer cell line AGS was transfected with PATL1 interference vector，and the interference effect was evaluated by RT-qPCR. The effects of PATL1 on the proliferation and migration of AGS were detected by cell counting kit-8 ( CCK-8) ，Transwell test and scratch healing test．The effects of interference with PATL1 on the expression of cel- lular-myelocytomatosis viral oncogene ( c-Myc) and autophagy related 7 ( ATG7) proteins in gastric cancer cells were detected by Western blot assay. @*Results @#RT-qPCR showed that the expression of PATL1 in human gastric cancer tissue was higher than that in normal gastric tissue (P＜0. 001) ，and PATL1 was correlated with the progno- sis of patients with enteric gastric cancer (P＜0. 000 1) ．After PATL1 was knocked down，the number of prolifera- ting and migrating gastric cancer cells decreased (P＜0. 05) ．Western blot test results showed that the expression level of ATG7 protein decreased after PATL1 was knocked down (P＜0. 05) ．@*Conclusion @#PATL1 may inhibit the proliferation and migration of gastric cancer cells through crosstalk with c-Myc and ATG7 .

Correlations of β-catenin expression with clinical efficacy of tyrosine kinase inhibitors and prognosis of advanced lung adenocarcinoma patients with epidermal growth factor receptor mutations / 肿瘤研究与临床

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

Progress of therapeutic efficacy and predictive indicators of neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 肿瘤研究与临床

The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy(nCRT) followed by surgery. The therapeutic efficacy of patients after nCRT differs greatly. Effective use of nCRT can accurately predict the efficacy and help patients avoid damage caused by excessive treatment. This article describes the main methods of current nCRT and newly proposed concepts, such as totally neoadjuvant therapy, summarzies its impact on the efficacy of locally advanced rectal cancer, introduces the potential predictive biomarkers of efficacy evaluation for nCRT and the latest advances in clinical, histological and molecular predictors, and discusses the potential value of efficacy prediction in nCRT .

Hypercalin B alleviates nonalcoholic steatohepatitis progression via suppressing mTORC1 signaling pathway / 药学学报

The global incidence rate of nonalcoholic steatohepatitis (NASH) continues to rise. The pathogenesis of NASH is complex, and there is no effective clinical treatment. Previous study has shown that DEAD box protein 5 (DDX5) can significantly alleviate the NASH process in mice. This study screened the natural product library of the research group and found that the active compound hypercalin B (HB) in Hypericum beanii N. Robson, a traditional Chinese medicine, can upregulate the expression of DDX5 protein in a dose-dependent manner. In this study, an in vitro model of NASH stimulated by palmitic acid (PA) and an animal model of NASH induced by the methionine- and choline-deficient diet (MCD) were constructed. Different concentrations of HB were used to investigate the effect and mechanism of HB in alleviating NASH progression. All animal experiments in this paper were approved by the Ethics Committee of China Pharmaceutical University (NO: 2021-02-003). In vitro model results showed that HB significantly reduced the intracellular lipid deposition induced by free fatty acid (FFA). Animal experiments showed that HB improved liver injury by significantly reducing lipid accumulation in the liver of NASH mice, and reducing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels. Moreover, HB could inhibit liver inflammation by reducing the mRNA levels of liver pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNFα). Further research showed that HB could reduce the phosphorylation level of the mechanical target of rapamycin (mTOR) and reduce the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), thereby improving lipid metabolism and alleviating NASH progression, and the effects of HB against NASH were dependent on DDX5. In conclusion, HB can improve lipid metabolism and inhibit inflammatory activation by suppressing mTORC1 pathway via upregulating DDX5 protein, and showed promising anti-NASH activity in vitro and in vivo.

Generation of traditional Chinese medicine prescription driven by generative artificial intelligence GPT-4 / 中国药房

OBJECTIVE To evaluate the safety and suitability of traditional Chinese medicine prescriptions generated by generative artificial intelligence （AIGC）， and to provide research ideas for empowering the traditional Chinese medicine industry with AIGC. METHODS Using the 2020 edition of Chinese Pharmacopoeia and the 5th edition of Traditional Chinese Medicine as corpus， GPT-4 and the real-time networking model developed based on GPT-4 （referred to as the “networking model”） were used for deep learning. The clinical cases included in the consensus of traditional Chinese medicine experts in recent years were extracted manually to regenerate prescriptions based on diagnosis using the GPT-4 model and networking model； traditional Chinese medicine experts conducted blind evaluation and scoring of GPT-4 generated prescriptions， networking model generated prescriptions， and expert consensus prescriptions. At the same time， Turing testing was used to evaluate whether the GPT-4 model and networking model had the same ability as human intelligence. RESULTS The average score of traditional Chinese medicine prescriptions generated by the GPT-4 model showed no statistically significant difference compared to manual prescriptions （P＞0.05）， while the average score of prescriptions generated by the networking model showed no statistically significant difference compared to traditional Chinese medicine prescriptions generated by the GPT-4 model （P＞0.05）. The proportion of model-generated prescriptions mistakenly judged as manual prescriptions in the Turing test was 51.11%. CONCLUSIONS The traditional Chinese medicine prescriptions generated by the GPT-4 model have reached a certain level of safety and suitability， and the GPT-4 model has passed the Turing test. The introduction of AIGC in the diagnosis and treatment process may provide technical support for the rational use of clinical traditional Chinese medicine.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary diseases with acute-moderate hypercapnic respiratory failure: a randomized controlled trial of non-inferiority / 中华急诊医学杂志

Objective:To compare the efficacy of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with moderate typeⅡ respiratory failure, to clarify the feasibility of HFNC in the treatment of AECOPD, and to explore the influencing factors of HFNC failure.Methods:This study was a randomized controlled trial of non-inferiority. Patients with AECOPD with moderate type Ⅱ respiratory failure [arterial blood gas pH 7.25-7.35, partial pressure of arterial blood carbon dioxide (PaCO 2)> 50 mmHg] admitted to the Intensive Care Unit (ICU) from January 2018 to December 2021 were randomly assigned to the HFNC group and NIV group to receive respiratory support. The primary endpoint was the treatment failure rate. The secondary endpoints were blood gas analysis and vital signs at 1 h, 12 h, and 48 h, total duration of respiratory support, 28-day mortality, comfort score, ICU length of stay, and total length of stay. Multivariate logistic regression analysis was used to evaluate the failure factors of HFNC treatment. Results:Totally 228 patients were randomly divided into two groups, 108 patients in the HFNC group and 110 patients in the NIV group. The treatment failure rate was 29.6% in the HFNC group and 25.5% in the NIV group. The risk difference of failure rate between the two groups was 4.18% (95% CI: -8.27%~16.48%, P=0.490), which was lower than the non-inferiority value of 9%. The most common causes of failure in the HFNC group were carbon dioxide retention and aggravation of respiratory distress, and the most common causes of failure in the NIV group were treatment intolerance and aggravation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (-29.02%, 95% CI -49.52%~-7.49%; P=0.004). After 1 h of treatment, the pH in both groups increased significantly, PaCO 2 decreased significantly and the oxygenation index increased significantly compared with baseline (all P < 0.05). PaCO 2 in both groups decreased gradually at 1 h, 12 h and 48 h after treatment, and the pH gradually increased. The average number of daily airway care interventions and the incidence of nasal and facial lesions in the HFNC group were significantly lower than those in the NIV group ( P < 0.05), while the comfort score in the HFNC group was significantly higher than that in the NIV group ( P=0.021). There was no significant difference between the two groups in the total duration of respiratory support, dyspnea score, ICU length of stay, total length of stay and 28-day mortality (all P > 0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health evaluation Ⅱ score (≥15), family NIV, history of cerebrovascular accident, PaCO 2 (≥60 mmHg) and respiratory rate (≥32 times/min) at 1 h were independent predictors of HFNC failure. Conclusions:HFNC is not inferior to NIV in the treatment of AECOPD complicated with moderate type Ⅱ respiratory failure. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

Discussion on hot issues in liver transplantation for hepatocellular carcinoma / 中华消化外科杂志

Liver diseases are common in China and the incidence and mortality of primary liver cancer are among the top in the world. As one of the therapeutic methods for hepatocellular carcinoma (HCC), liver transplantation has become an important technique in hepatic surgery. Most of patients with HCC have progressed to stage B or C of Barcelona Clinic Liver Cancer staging when diagnosed. How to reduce the dropout rate of HCC patients due to the progression of tumor when waiting for liver transplantation, develop individualized immunosuppressant plans for HCC patients after liver transplantation, and accurately manage patients with HCC recurrence after liver transplan-tation are the current hotspots of research. The authors review the relevant literature, summarize the treatment experience, and discuss the hot issues in liver transplantation for HCC, in order to provide reference for related treatment.

Effect of lung protective ventilation on lung ventilation function, serum serum Clara cell protein 16 level and prognosis in patients undergoing gynecological laparoscopic surgery / 中国医师进修杂志

Objective:To analyze the effect of lung protective ventilation on lung ventilation function and serum Clara cell protein 16 (CC16) level in patients undergoing gynecological laparoscopic surgery.Methods:The clinical data of 80 gynecological patients who underwent laparoscopic surgery in Yancheng City Jianhu County People′s Hospital from October 2018 to December 2020 were randomly divided into group A and group B by random number table, each group with 40 cases. The patients in group A were treated with intermittent positive-pressure ventilation, and the patients in group B were ventilated with whole course ventilation mode. The pulmonary ventilation function, CC16 level and postoperative pulmonary complications were observed before anesthesia, 10 min of pneumoperitoneum, 30 min of pneumoperitoneum, 5 min of pneumoperitoneum stop and 2 h after operation. The patients were divided into groups according to whether with pulmonary complications, and their pulmonary ventilation function and serum CC16 level were compared. The predictive value of the above indexes for pulmonary complications was analyzed by receiver operating characteristic (ROC) curve.Results:Repeated measurement analysis of variance showed that alveolar arterial oxygen differential pressure (PA-aDO 2) were significant differences in time point factors, time point interaction factors and group factors ( P<0.05); CC16 index were significant differences in time point factor and group factor ( P<0.05). According to the observation from postoperative to discharge, 4 patients (10.0%) in group A had pulmonary complications, 15 cases (37.5%) had pulmonary complications in group B, the levels of PA-aDO 2 and CC16 in patients with complications were significantly higher than those in patients without complications: group A:(332.9 ± 2.0) mmHg (1 mmHg = 0.133 kPa) vs. (290.4 ± 13.2) mmHg, (53.5 ± 1.5) μg/L vs. (39.5 ± 6.5) μg/L; group B: (339.1 ± 8.8) mmHg vs. (305.7 ± 17.9) mmHg, (41.5 ± 4.2) μg/L vs. (39.7 ± 5.8) μg/L, there were statistical differences ( P<0.05). ROC curve analysis showed that the area under the curve(AUC) of PA-aDO 2 and CC16 in predicting pulmonary complications in group A were 0.882 and 0.833, in group B was 0.885 and 0.731. Conclusions:Lung protective ventilation has little effect on lung ventilation function and serum CC16 in patients with gynecological laparoscopic surgery, and the probability of pulmonary complications is lower. The pulmonary ventilation function and CC16 have certain value in predicting postoperative pulmonary complications.

Status survey and countermeasures for trainees in standardized residency training of ultrasound professional base under the novel coronavirus pneumonia epidemic / 中华医学教育探索杂志

Objective:To investigate the behavior and emotion of trainees (residents) in the standardized residency training under the novel coronavirus pneumonia (NCP) epidemic, and adjust the training plan and mode of standardized residency training during the NCP epidemic according to the survey results.Methods:A real-name closed questionnaire survey was conducted among 40 residents (27 ultrasound majors and 13 other majors) in ultrasound department using the "Questionnaire Star" WeChat applet, including basic personal information, questions related to NCP, behavioral change survey, behavioral attitude survey and emotional status survey. All the collected data were further statistically analyzed by Chi-square test and rank sum test using SPSS 19.0Results:There were forty valid questionnaires and the participation rate was 100.0%. The accuracy of 24 NCP-related questions was not significantly different between residents majoring in ultrasound and other specialties [92.0%(596/648) vs. 93.6%(292/312), P>0.05]. All the residents had a good understanding of NCP. The main behaviors of going out were significantly reduced, while various behaviors of being at home were significantly increased. Their interest in learning declined. When the epidemic happened (or possibly) in the community or village they lived in, their negative emotions, such as nervousness, fear pessimism and depression, were obviously expressed. Network teaching and evaluation through WeChat public number were adopted and we guided residents to adjust their home behaviors and emotions according to the survey results. Conclusion:Under the NCP epidemic, the behaviors and emotions of residents had been extensively changed. The training center should adjust the teaching plan and mode of training in time, and provide more counselling service in psychology and learning for residents during the epidemic.