Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate the predictive value of serum Nesfatin-1 and 25-hydroxyvitamin D3[25(OH)D3]levels for the short-term prognosis of status epilepticus(SE)in children.Methods A total of 104 children with SE admitted to the hospital from March 2020 to March 2023 were enrolled in the study,and the clinical data of the children were collected.According to the Glasgow outcome Scale(GOS)score at dis-charge,the children were divided into a good prognosis group(equal to 5 points)and a poor prognosis group(＜5 points).Univariate analysis and multivariate Logistic regression were used to analyze whether serum Nesfatin-1 and 25(OH)D3 levels were risk factors for poor short-term prognosis in children with SE.The re-ceiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum Nesfatin-1 and 25(OH)D3 levels for the short-term poor prognosis in children with SE.Results At discharge,85 children[81.73％(85/104)]with a GOS score of 5 were included in the good prognosis group,and 19 children[8.27％(19/104)]with a GOS score of＜5 were included in the poor prognosis group.There was no significant differ-ence in gender,age,previous history of epilepsy,and seizure types between the two groups(P＞0.05).There were significant differences in the duration of SE,the time from medication to seizure cessation,electroenceph-alogram(EEG)results,head CT results,and serum Nesfatin-1 and 25(OH)D3 levels between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that SE duration＞60 min,abnormal head CT results,serum Nesfatin-1 and 25(OH)D3 levels were independent risk factors for the short-term poor progno-sis of children with SE(OR=1.945,2.343,1.731,1.505;P＜0.05).The area under the ROC curve of serum Nesfatin-1 and 25(OH)D3 levels combined to predict poor short-term prognosis of children with SE was 0.840(95％CI:0.732-0.949),which was better than that of serum Nesfatin-1 and 25(OH)D3 levels alone[0.607(95％CI:0.453-0.761),0.742(95％CI:0.604-0.880)],respectively.Conclusion Serum Nesfatin-1 and 25(OH)D3 levels are risk factors for poor prognosis in children with SE,and the combination of them has high predictive value for poor prognosis in children with SE.

BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.

This study intends to establish a colorectal cancer(CRC)organoid model,expand and isolate CRC-reactive tumor-infiltrating lymphocytes(TILs),screen tumor-specific T cell receptors(TCRs)and perform functional verification,in order to provide a technological platform and research foundation for the clinical transformation of individualized adoptive T-cell immunotherapy for colorectal cancer.An organoid model derived from colon cancer patient tissues was constructed using in vitro 3D culture techniques,which then subjected to HE staining and immunohistochemistry for detecting morphological characteristics and representative molecular expression.Subsequently,CRC organoids were co-cultured with TILs for sorting reactive TILs using flow cytometry,and the characteristics of reactive TCR clones was analyzed through single T cell receptor gene cloning technology.Furthermore,the function of TCRs was verified through cytotoxicity experiments.Morphological analysis and representative molecules(CK20 and CDX2)expression indicated that there is high similarity between colorectal cancer organoids and patient tumors.In the in vitro expanded and cultured TILs,colorectal cancer-reactive T cells with upregulated CD137 expression and increased IFN-γ secretion were screened out successfully,among which TCR2-T cells demonstrated superior tumor reactivity and in vitro tumor killing function.In conclusion,a platform for screening and function validation of reactive TCRs based on CRC-Org has been established,providing a technological platform for the translational application of individualized T-cell therapy for colorectal cancer.

Objective:To investigate the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) gene on the proliferation and apoptosis of colorectal adenocarcinoma cells in vitro, and the role of Nrf2 gene in regulation of epithelial-mesenchymal transition (EMT) pathway.Methods:Three Nrf2 small interfering RNA (siRNA) sequences were designed and synthesized, namely siRNA-223, siRNA-538 and siRNA-756, and the unrelated sequences were designed and synthesized. The plasmids carrying various siRNA sequences of Nrf2 were constructed, and the plasmids carrying siRNA sequences and the plasmids carrying unrelated sequences were transfected into human colorectal adenocarcinoma Caco-2 cells, namely interference group and empty vector group, respectively. Additionally, Caco-2 cells without any treatment were used as the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) methods were used to detect the relative expression of Nrf2 gene in transcription and translation levels in each group of cells, in order to verify the interference effect of Nrf2; the siRNA with the best interference effect was selected for subsequent experiments. CCK-8 method was used to detect the proliferation ability of each group of cells (expressed as absorbance value); RT-qPCR was used to detect the relative expression of EMT pathway-related factors [vimentin (Vim), N-cadherin (N-cad) and E-cadherin (E-cad)] in transcription level in each group of cells; WB method was used to detect the expression of pro-apoptotic protein Bax in each group of cells.Results:The results of RT-qPCR and WB methods showed that compared with the control group and the empty group, the relative expression of Nrf2 gene in transcription and translation levels in Caco-2 cells of the siRNA-756 interference group were the lowest, and the differences were statistically significant (all P < 0.05). The CCK-8 results showed that the absorbance values of Caco-2 cells in the control group, empty group and siRNA-756 interference group after 48 hours of culture were (100±5)%, (94±4)% and (82±5)%, respectively; compared with the control group and the empty group, the siRNA-756 interference group had lower absorbance value, and the differences were statistically significant (all P < 0.05). The results of RT-qPCR method showed that the relative expression of Vim and N-cad in transcription level in the siRNA-756 interference group were higher than those in the control group and the empty vector group, and the differences were statistically significant (all P < 0.05); the relative expression of E-cad in transcription level was lower than those in the control group and the empty vector group, and the differences were statistically significant (both P < 0.05). The results of WB method showed that the relative expression of Bax protein in the siRNA-756 interference group was higher than that in the control group, and the difference was statistically significant ( P < 0.05). Conclusions:Interference with Nrf2 expression in vitro can weaken the proliferation and anti-apoptotic abilities of human colorectal adenocarcinoma Caco-2 cells. The mechanism may be that Nrf2 regulates the expression of Vim, N-cad and E-Cad in the EMT pathway to enhance the EMT ability of tumor cells.

Urinary system tumors include malignancies of the bladder, kidney, and prostate, and present considerable challenges in diagnosis and treatment. The conventional therapeutic approaches against urinary tumors are limited by the lack of targeted drug delivery and significant adverse effects, thereby necessitating novel solutions. Intelligent nanomedicine has emerged as a promising therapeutic alternative for cancer in recent years, and uses nanoscale materials to overcome the inherent biological barriers of tumors, and enhance diagnostic and therapeutic accuracy. In this review, we have explored the recent advances and applications of intelligent nanomedicine for the diagnosis, imaging, and treatment of urinary tumors. The principles of nanomedicine design pertaining to drug encapsulation, targeting and controlled release have been discussed, with emphasis on the strategies for overcoming renal clearance and tumor heterogeneity. Furthermore, the therapeutic applications of intelligent nanomedicine, its advantages over traditional chemotherapy, and the challenges currently facing clinical translation of nanomedicine, such as safety, regulation and scalability, have also been reviewed. Finally, we have assessed the potential of intelligent nanomedicine in the management of urinary system tumors, emphasizing emerging trends such as personalized nanomedicine and combination therapies. This comprehensive review underscores the substantial contributions of nanomedicine to the field of oncology and offers a promising outlook for more effective and precise treatment strategies for urinary system tumors.

Objective:To investigate the application effect of Press-Z-track-Turn (PZT) intramuscular injection on the extravasation, local reaction, local pain after injection and patient satisfaction after Fulvestrant injection.Methods:Used a self-controlled study, 63 patients who underwent bilateral intramuscular injection of Fluvastatin in the outpatient injection room of Tianjin Medical University Cancer Hospital from August to October 2022 were conveniently selected. The observation time was two treatment cycles after inclusion in this study. Before the injection of the first treatment cycle, a coin toss was used to randomly decide to use traditional intramuscular injection and PZT intramuscular injection method for injection and record. After 28 days, another injection method was used, with a total of 126 injections per injection method. Observed the extravasation of drug solution and local reactions at the injection site within 7 days after injection using two injection methods, as well as the pain and satisfaction of patients within 7 days after injection.Results:The extravasation rate of drug solution for the PZT intramuscular injection was 1.59% (2/126), which was lower than 7.14% (9/126) for the traditional intramuscular injection, and the difference was statistically significant ( χ2=4.66, P<0.05); the incidence of mild and moderate local reactions for the PZT intramuscular injection was 3.97% (5/126) and 1.59% (2/126), respectively, lower than that for the traditional intramuscular injection 11.11% (14/126) and 5.56% (7/126), and the difference was statistically significant ( χ2=8.26, P<0.05); the pain score of the PZT intramuscular injection was (2.08 ± 0.85) points, lower than that of the traditional intramuscular injection (5.03 ± 1.06) points, and the satisfaction score of the PZT intramuscular injection was (23.68 ± 1.64) points, higher than that of the traditional intramuscular injection (20.10 ± 2.58) points. The difference was statistically significant ( t=-17.24, 9.16, both P<0.01). Conclusions:PZT intramuscular injection can effectively reduce the overflow rate, the incidence of grade 1 and 2 local reactions and the degree of pain of patients, and improve patient satisfaction, which is worthy of clinical application.

Objective:To understand the thyroid function of the physical examination population in Tangshan area, and analyze the effects of thyroid function on blood lipids, fasting blood glucose (FPG), and serum 25 hydroxyvitamin D [25(OH)D].Methods:A population from the Tangshan area who underwent physical examinations at the Kailuan General Hospital from June 2020 to June 2021 was selected as the study subjects and the levels of their thyroid serological indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (TT3), and thyroid hormone (TT4)] were tested. According to thyroid function, they were divided into normal group, hyperthyroidism group, hypothyroidism group, subclinical hyperthyroidism group, and subclinical hypothyroidism group. We compared the blood lipid indicators [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], FPG, and 25(OH)D levels in different subgroups, and the Pearson correlation analysis was used to investigate the correlation between TSH levels and blood lipids, FPG, and 25(OH)D levels.Results:In this study, 2 884 subjects were selected from the physical examination population in Tangshan area. The proportion of people with abnormal thyroid function was 12.03%(347/2 884), among which the proportion of subclinical thyroid function abnormal population in the total thyroid function abnormal population was 80.69%(280/347). As men age, the proportion of thyroid dysfunction in the age groups of 21-<30 years old, 30-<40 years old, 40-<50 years old, and ≥50 years old was 5.06%(4/79), 7.52%(33/439), 8.91%(53/595), and 9.95%(66/663), respectively. The proportion of thyroid dysfunction in the above age group of women was 14.02%(15/107), 15.06%(61/405), 15.47%(67/433), and 29.45%(48/163). The serum TG, TC, LDL-C, and 25(OH)D levels in the hyperthyroidism group were lower than those in the normal group, while HDL-C and FPG levels were higher than those in the normal group, with statistically significant differences (all P<0.05). The serum TG and TC in the hypothyroidism group were higher than those in the normal group, while FPG and 25(OH)D were lower than those in the normal group, with statistically significant differences (all P<0.05). TSH levels were positively correlated with TC and LDL-C, while negatively correlated with FPG and 25(OH)D (all P<0.05). Conclusions:Subclinical thyroid dysfunction is the main cause of thyroid dysfunction in the Tangshan area, and TSH levels are correlated with blood lipids, fasting blood glucose, and serum 25(OH)D levels.

Renal interstitial fibrosis （RIF） is the main pathological feature of chronic kidney disease caused by a variety of factors. "Kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" is the main pathogenesis of RIF. The deficiency of healthy Qi will influence the kidney Qi， resulting in kidney deficiency and unsmooth qi transformation. As a result， phlegm， heat， stasis， toxin and other excess pathogens block the kidney collaterals， forming miniature masses. The masses accumulate in the renal collaterals， finally leading to RIF. Autophagy is a key process that keeps your body's cells in proper balance by taking aged or damaged components in a cell and recycling them. It is involved in the occurrence and development of RIF. The metabolism of excess pathogens such as phlegm， heat， stasis， and toxin in vivo is related to the degradation and reabsorption of autophagy. Autophagy is a way to eliminate phlegm， heat， stasis， toxin and other excess pathogens. Autophagy dysfunction will cause the accumulation of phlegm， heat， blood stasis， toxin and other excess pathogens， further the stasis of the kidney collaterals， miniature mass in kidney， and finally RIF. Kidney deficiency and blood stasis in collateral are the root cause of autophagy dysfunction， and the miniature mass of renal collateral is the manifestation of autophagy dysfunction. Autophagy dysfunction and miniature mass of renal collateral have the same pathological evolution. In this paper， based on the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" of RIF and RIF-autophagy relationship， this paper discusses the "kidney deficiency and blood stasis in collateral-autophagy dysfunction-miniature mass of renal collateral" relationship in RIF and comprehensively interprets the scientific connotation of the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral"， which is expected to lay a basis for explaining the role of autophagy in TCM theory and for the treatment of RIF and research on the mechanism.

Chronic renal failure （CRF）， a common outcome of various chronic kidney diseases， is characterized by retention of metabolites and toxins， water-electrolyte imbalance， acid-base disturbance， and various symptoms in diverse systems. The incidence and progression of this disease are influenced by many factors， particularly the change of intestinal flora. Previous research shows that the intestinal flora interacts with CRF. For CRF patients， the metabolic waste fails to be cleared in time due to the gradual decline of renal function and thus accumulates in vivo. Moreover， CRF changes the composition of intestinal flora， damages intestinal barrier， and accelerates the synthesis of intestinal uremic toxins and the accumulation in blood. As a result， the renal injury is aggravated. The imbalance of intestinal flora can induce acute kidney injury， increase cardiovascular complications， stimulate immune inflammatory responses， and thus aggravate the progression of CRF. Microbiota-targeted therapy for CRF has become the research focus. According to traditional Chinese medicine， kidney disease is related to the intestine and kidney disease should be treated from the intestine. Spleen and kidney are in the closest relationship with the pathogenesis of CRF and the intestinal flora. Chinese medicine， which features multiple targets， multiple effects， and multiple components， acts on the "gut-kidney axis". It is thus superior in the clinical treatment of CRF and the regulation of intestinal flora. To be specific， it intervenes in intestinal flora to delay the process of CRF. In this paper， based on the correlation of traditional Chinese medicine theory with intestinal flora and CRF， this paper reviewed the interaction between intestinal flora and CRF and traditional Chinese medicine intervention in the intestinal flora for the treatment of CRF， which is expected to serve as a reference for the clinical treatment of this disease and the drug development.