Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

Objective:To evaluate the utility of ultrasonographic monitoring of the rectus femoris muscle—specifically, the rates of change in thickness and cross-sectional area (CSA)—in assessing nutritional status and long-term functional outcomes in patients with sepsis.Methods:In this prospective observational study, sepsis patients admitted to the ICU of the Second Affiliated Hospital of Soochow University between October 2023 and October 2024 were classified by nutritional status at discharge using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Differences in serial ultrasound-measured rectus femoris thickness and CSA on days 1, 3, 5, and 7 were compared between malnourished and non-malnourished groups. The predictive value of these ultrasound parameters for malnutrition was analyzed. Functional prognosis was assessed using the Sarcopenia Assessment Scale, Short Physical Performance Battery, and Manual Muscle Testing, with correlations to muscle changes examined.Results:Of the 71 enrolled patients (median age 73.00 [ IQR: 61.00–80.00]; 47.89% female, 52.11% male), those with malnutrition showed significantly greater variation rates in rectus femoris thickness and CSA on days 3, 5, and 7 compared to the non-malnourished group ( P < 0.05). ROC analysis revealed that the day-7 CSA variation rate had the highest predictive value for malnutrition (AUC = 0.817, 95% CI: 0.713-0.930). These muscle variation rates also correlated strongly with conventional nutritional markers such as BMI, albumin, and urea. Similarly, patients with impaired functional outcomes exhibited higher variation rates in muscle parameters on days 3, 5, and 7 ( P < 0.05), with the day-7 CSA variation rate being most predictive of functional prognosis (AUC = 0.749, 95% CI: 0.632-0.867). Conclusions:Ultrasonographic assessment of rectus femoris thickness and CSA variation rates provides a valuable tool for evaluating nutritional status and predicting functional prognosis in sepsis patients, outperforming traditional biomarkers. This method shows promise for guiding individualized nutrition support and rehabilitation strategies to improve long-term outcomes.

Objective To construct a predictive model for clinical pregnancy outcomes in frozen-thawed embryo transfer(FET)cycles in women with advanced maternal age(age≥35 years)and to analyze its influencing factors.Methods A retrospective analysis was conducted on the clinical data of 2717 older patients who underwent FET treatment at the First Affiliated Hospital of Kunming Medical University from January 2018 to December 2023.These Patients were divided into a clinical pregnancy group(n=851)and a non-clinical pregnancy group(n=1866)based on whether the clinical pregnancy had occurred.The general characteristics and transplantation details of the two groups were compared,and a logistic regression analysis model was constructed.Results The clinical pregnancy rate(CPR)was 31.32%.The CPR for women aged 35-40 years(40.06%)was higher than that for women aged≥40 years(19.35%),with a statistically significant difference(χ2=133.371,P<0.05).The model results showed that the higher anti-Mullerian hormone(AMH)levels(OR=1.053,95%CI:1.012-1.095),the more high-quality blastocysts were transferred(OR=1.704,95%CI:1.143-2.542;OR=2.861,95%CI:1.921-4.262);the more high-quality blastocysts were transferred(OR=2.033,95%CI:1.077-3.836;OR=3.886,95%CI:2.035-7.420),the thicker the endometrial lining on the day of transfer(OR=1.150,95%CI:1.092-1.212)and it could increase the probability of clinical pregnancy.However,for women over 40 years of age(OR=0.551,95%CI:0.437-0.694)and secondary infertility(OR=0.704,95%CI:0.552-0.896),the probability of clinical pregnancy would be reduced;ROC curve analysis results showed that the AUC for predicting clinical pregnancy occurrence in the training set and validation set of the predictive model were 0.723(95%CI:0.699-0.748)and 0.726(95%CI:0.689-0.764),respectively,with cutoff values of 0.262 and 0.260 and the model fit was good(P>0.05).Conclusion Female age,AMH level,type of infertility,number of high-quality embryos(cleavage embryos,blastocysts)transferred,and endometrial thickness on the day of transfer are important factors affecting FET cycles in advanced maternal age women.The constructed prediction model based on these factors has a certain predictive ability for clinical pregnancy.

AIM: To observe the changes of corneal densitometry(CD)in patients with keratoconus after corneal cross-linking(CXL).METHODS: Retrospective study. A total of 32 patients(43 eyes)with keratoconus in Ningxia Eye Hospital from April 2020 to April 2022 were selected. Pentacam analysis system divided the cornea into three layers: anterior 120 μm, middle layer and posterior 60 μm, and divides it into five regions with diameters of 0-2, 2-6, 6-10, 10-12 mm and full diameter according to the diameter, and measures the CD in different ranges. The changes of CD were compared before operation and at 1, 3 and 6 mo after operation.RESULTS: There were differences in uncorrected visual acuity, best corrected visual acuity and intraocular pressure before and 6 mo after operation(all P<0.05), and there was no difference in corneal endothelial cells(P=0.477). CD reached its peak at 1 mo after operation, and decreased at 3 mo and 6 mo after operation, but it was still higher than that before operation. There is a significant positive correlation between CD and Kmax in the anterior layer and the whole layer(r=0.164, P=0.016; r=0.152, P=0.023).CONCLUSION: The values of CD peaked at 1 mo after CXL, then it gradually decreased, tending to become stable at 6 mo postoperatively.

Objective:To observe the correlation between blood cell-related inflammatory markers and diabetic retinopathy (DR).Methods:A cross-sectional study. From June 2020 to February 2022, the phase Ⅰ data of Beichen Eye Study in Tianjin Medical University Eye Hospital were included in the study. The research contents included questionnaires, routine systemic and ocular examinations, and laboratory blood cell-related indicators including mean platelet volume (MPV), platelet distribution width (PDW), neutrophils, and lymphocytes were performed. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The diagnosis and classification of DR referred to the international clinical classification standard of DR. Monocular or binocular DR was defined as DR patients. Participants were categorized into different groups based on whether they had diabetes and whether they had DR. The groups included the no-diabetes group, the diabetes without DR group, and the DR group. The Kruskal-Wallis H test was used for the comparison of quantitative data among multiple groups. Wilcoxon test was used for comparison between the two groups. The χ2 test was used to compare the categorical variables between groups. The variables was adjusted step by step, an unadjusted univariate model was built and the different parameters of the model Ⅰ, Ⅱ, Ⅲ were adjusted. The correlation between MPV, PDW, NLR, PLR, and DR in different models was analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different NLR models for DR. Results:A total of 3 328 subjects were recruited. Among them, 1 121 (33.68 %, 1 121/3 328) were males and 2 207 (66.32 %, 2 207/3 328) were females. The median age of the included participants was 61.84 (6.05) years. The no-diabetes group, the diabetes without DR group, and the DR group were 2 679, 476, and 173, respectively. There was no significant difference in MPV and PLR among the three groups ( H=5.98, 1.94; P=0.051, 0.379). However, compared with no-diabetes group and the diabetes without DR group, PDW and NLR in the DR group showed an upward trend. In model Ⅲ with completely adjusted related factors, NLR was an independent risk factor for DR in no-diabetes group and DR group [odds ratio ( OR)=1.440, 95% confidence interval ( CI) 1.087-1.920, P=0.041], diabetes without DR group and DR group [ OR=1.990, 95% CI 1.440-2.749, P<0.001]. The results of ROC curve analysis showed that the diagnostic efficiency of NLR model Ⅲ was the highest, the area under the curve was 0.751 (95% CI 0.706-0.796, P<0.001), the optimal cutoff value was 0.390, and the sensitivity and specificity were 74.3% and 64.8%, respectively. Conclusions:The NLR of the DR group is significantly higher than that of the no-diabetes group and diabetes without DR group. NLR is an independent risk factor for DR.

Background With the aging of China's population, cognitive impairment in the elderly is receiving increasing public attention. Screening and intervention of people with mild cognitive impairment (MCI) are of great significance to prevent and reduce the occurrence of cognitive impairment. Objective To understand the prevalence and explore potential influencing factors of MCI in the elderly in Songjiang District, Shanghai, and to provide scientific basis for promoting early screening of cognitive impairment and precise intervention of MCI in the elderly in this area. Methods A cross-sectional study design was adopted. From August to October 2022, using multi-stage random sampling, 1800 elderly residents aged 60 years and above were screened for cognitive impairment in 6 neighborhood/village committees in 6 towns in Songjiang District. The survey questionnaires included a sociodemographic questionnaire, a health status and lifestyle questionnaire, the Instrumental Activities of Daily Living (IADL), the Patient Health Questionnaire (PHQ-9), and the Mini-Mental State Examination (MMSE). Prevalence rates of MCI among the elderly by selected social demographic characteristics, health status, and lifestyle were estimated, and potential influencing factors of MCI were evaluated by binary logistic regression. Results A total of 209 elderly residents with MCI and 1591 healthy elderly residents were detected, and the prevalence of MCI in the elderly aged 60 and above was 11.6% in Songjiang District. Being physically active (OR=0.556, 95%CI: 0.399, 0.774) reduced the risk of MCI. Illiteracy (OR=1.810, 95%CI: 1.239, 2.644), primary school education level (OR=3.454, 95%CI: 2.342, 5.092), non-participation in social activities (OR=1.945, 95%CI: 1.360, 2.781), IADL damaged (OR=3.173, 95%CI: 2.137, 4.712), and depression (OR=1.957, 95%CI: 1.112, 3.443) increased the risk of MCI (P＜0.05). Conclusion The prevalence of MCI among the elderly in Songjiang District is lower than the national average. Educational level, physical activity, participation in social activities, IADL, and depression may be the influencing factors of MCI in the elderly. It is recommended to carry out early screening, early detection, and early intervention for cognitive impairment in the elderly. Improving involvement in physical exercise and increasing participation in social activities are encouraged. Special attention should be paid to the needs of vulnerable groups such as low education level and disabled elderly during a community MCI intervention program.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective To evaluate the agreement of four common HEp-2 indirect immunofluorescence assay(IFA)kits in the patients with antinuclear antibody(ANA)-associated rheumatic immune diseases(AARD)and the patients with non-autoimmune diseases(NAD).Methods The experiment in this study included two stages.In stage 1,the serum samples were randomly selected from 134 patients,and ANAs were detected by IFA at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from Janu-ary to June 2023.All of the samples were tested using four kinds of HEp-2 IFA kits,and the consistency of qualitative results was eval-uated by statistical analysis.The kit exhibited highest positive rate was defined as Kit X.In the stageⅡ,a total of 554 serum samples(from 218 AARD and 336 NAD patients)with positive results detected by initial screening of reagent X were selected during the same period,and then the samples were tested by the other three HEp-2 IFA kits.The patterns and titers of ANA were recorded,and a semi-quantitative evaluation system was established.The reproducibility of different patterns of ANA and the consistency of the results among varying clinical characteristics,fluorescence reaction intensities and positive reaction sites in nucleus was statistically analyzed.Results There were no significant differences of qualitative results among the results from four kits(P＞0.05).The highest positive rate ap-peared in the kit m(45.86%)which was deemed as the initial screening kit X.Significant differences in the consistency of ANA pat-terns were observed.The reproducibility scores of centromeric pattern and granular pattern were higher than those of homogeneous pat-tern,dense fine speckled pattern,nuclear cytoplasmic mixed pattern and other mixed pattern with significant difference(P＜0.05).The reproducibility score of simple pattern was higher than that of mixed patterns(P＜0.05).In the nucleoplasmic region,the consistency score of the AARD group was higher than that of NAD group(P＜0.01).The consistency scores of each reaction site increased with the rise of the intensity of reaction.In the three reaction parts(nucleoplasm,nucleolus and equatorial plate),the scores between the weak and strong fluorescence reaction intensity groups showed significant differences(P＜0.001).The lowest consistency score occurred in cytoplasmic region.Conclusion The clinical interpretation for IFA ANA reports should be more cautious for the results showing weak fluorescence intensity,mixed patterns,and staining positive cytoplasmic sites.For the choice for reagents,the clinical laboratories should be also mindful of the impacts of fluorescent secondary antibodies of anti-human immunoglobulin on the test results.The develop-ment of standardized official guidelines for the manufacture of HEp-2 IFA kits should be crucial initiative for enhancing the consistency of ANA detection and promoting mutual recognition for the results between laboratories.

Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.