The medicinal use of Malvae Semen has a long history. In this paper， by consulting the ancient materia medica， prescription， agronomy， literature and other aspects of the classics， the name， origin， evolution of scientific name， quality， harvesting and processing， functions and indications and others of Malvae Semen were systematically sorted out and verified， so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research， Shennong Bencaojing began to use Dongkuizi as the correct name， which was used in the past dynasties， and there were also aliases such as Kuicaizi， Huacai， and Kuizi. Through the original research， it can be seen that Kuicai is the mainstream original plant of Malvae Semen， that is， Malva verticillata var. crispa， the Alcea rosea and M. cathayensis are also used. In modern times， the seeds of Abutilon theophrasti have been passed off as Malvae Semen， while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties， the cultivation of Kuicai has been decreasing， while A. theophrasti is more common and easy to obtain， and Abutili Semen and Malvae Semen are similar in morphology and confused， which should be corrected. In addition， Malvae Fructus is a Mongolian customary medicinal herb， which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai， as an important vegetable in history， was widely cultivated and gradually shrunk after the Song dynasty， it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies， full grain， grayish brown color， no mud， and no impurities. The harvesting is generally in the autumn and winter. After drying， it is seeded， sieved peel and impurities， mashed， or slightly stir-fried to yellow-white color with gentle fire. It is sweet， cold and slippery in nature and taste， with the main effects of laxation， diuresis， lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity， promoting diuresis and removing nebula， the efficacy is quite different from that of Malvae Semen. Based on the results of textual research， it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas， the corresponding processing methods should be selected according to the requirements of drug processing in the formulas， while the raw products are recommended to be used if the processing is not specified.

The medicinal use of Malvae Semen has a long history. In this paper， by consulting the ancient materia medica， prescription， agronomy， literature and other aspects of the classics， the name， origin， evolution of scientific name， quality， harvesting and processing， functions and indications and others of Malvae Semen were systematically sorted out and verified， so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research， Shennong Bencaojing began to use Dongkuizi as the correct name， which was used in the past dynasties， and there were also aliases such as Kuicaizi， Huacai， and Kuizi. Through the original research， it can be seen that Kuicai is the mainstream original plant of Malvae Semen， that is， Malva verticillata var. crispa， the Alcea rosea and M. cathayensis are also used. In modern times， the seeds of Abutilon theophrasti have been passed off as Malvae Semen， while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties， the cultivation of Kuicai has been decreasing， while A. theophrasti is more common and easy to obtain， and Abutili Semen and Malvae Semen are similar in morphology and confused， which should be corrected. In addition， Malvae Fructus is a Mongolian customary medicinal herb， which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai， as an important vegetable in history， was widely cultivated and gradually shrunk after the Song dynasty， it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies， full grain， grayish brown color， no mud， and no impurities. The harvesting is generally in the autumn and winter. After drying， it is seeded， sieved peel and impurities， mashed， or slightly stir-fried to yellow-white color with gentle fire. It is sweet， cold and slippery in nature and taste， with the main effects of laxation， diuresis， lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity， promoting diuresis and removing nebula， the efficacy is quite different from that of Malvae Semen. Based on the results of textual research， it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas， the corresponding processing methods should be selected according to the requirements of drug processing in the formulas， while the raw products are recommended to be used if the processing is not specified.

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective·To analyze the expression changes of adhesion G protein-coupled receptor F1(ADGRF1)in the occurrence and development of pancreatic ductal adenocarcinoma(PDAC),and explore the impact of ADGRF1 on the proliferation of PDAC cells and the potential molecular mechanisms that promote PDAC progression.Methods·The expression of ADGRF1 at mRNA level was analyzed based on the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database,respectively.The expression of ADGRF1 in normal pancreatic ductal epithelial cells(hTERT-HPNE)and various PDAC tumor cells was detected by using real-time fluorescence quantitative PCR(qPCR)and Western blotting.Immunohistochemical staining(IHC)was used to detect the differential expression of ADGRF1 in cancer tissues and adjacent tissues of PDAC patients.After knocking down ADGRF1 with small interfering RNA(siRNA)transfection,the changes in the proliferation ability of PDAC AsPC-1 and SW1990 cells were detected through CCK8 assay and plate cloning experiment.Stable overexpression of ADGRF1 was constructed in PDAC Patu8988 cell line,and the proliferation changes induced by overexpression of ADGRF1 were evaluated through CCK8 assay.RNA sequencing(RNA-seq),gene set enrichment analysis(GSEA),and immune infiltration analysis were utilized to predict signaling pathways associated with ADGRF1-mediated promotion of PDAC cancer progression.Results·Analysis of the TCGA database and GEO database revealed higher expression of ADGRF1 mRNA in PDAC tissues compared to normal pancreatic tissues(all P=0.000).qPCR and Western blotting results demonstrated up-regulation of ADGRF1 mRNA and protein levels in various PDAC cells compared to hTERT-HPNE cells(all P<0.05).IHC results confirmed higher ADGRF1 expression in PDAC cancer tissues compared to adjacent tissues.Furthermore,downregulation of ADGRF1 inhibited the proliferation of PDAC AsPC-1 and SW1990 cell lines,while overexpression of ADGRF1 promoted the proliferation of Patu8988 cells(all P<0.05).RNA-seq,GSEA enrichment analysis,and immune infiltration analysis revealed that ADGRF1 expression was related to signaling pathways such as interferon-α(IFN-α),tumor necrosis factor-α(TNF-α),and nuclear factor κB(NF-κB).Conclusion·ADGRF1 is highly expressed in PDAC cells and tissues,and promotes the proliferation of PDAC cells via immune-related signaling pathways.

Objective To quantitatively measure the morphological parameters of type Ⅱ accessory navicular(AN)in CT images and analyze the mechanical changes in the foot caused by painful type Ⅱ AN.Methods The CT images of 51 patients with type Ⅱ AN were analyzed retrospectively;According to whether the medial foot was painful,we divided the data into two groups,including the pain type Ⅱ AN group(case group)and the non-pain type Ⅱ AN group(control group).The measured data included the navicular and medial joint space(MeJS),middle joint space(MiJS),lateral joint space(LJS),talar-accessory navicular distance(TAND),the maximum diameter(MaD)and minimum diameter(MiD)of AN,and the difference of the relevant data using independent sample t-test was measured.Results Compared with the control group,the MeJS,MiJS,and LJS in the case group showed that the joint space of painful type Ⅱ AN was widened,and there was a significant difference(P＜0.05).Compared with the control group,the TAND,MaD,and MiD of the case group had no significant change,and there was no significant difference(P＞0.05).Conclusion In pain-ful type Ⅱ AN foot,the posterior tibial tendon(PTT)is attached to AN,which destroys the balance of force on the foot,resulting in the widening of the distance between the navicular and AN.

Objective To investigate the value of breast MRI-abbreviated protocol(BMRI-AP)compared with full field digital mammography(FFDM)and breast MRI-full diagnostic protocol(BMRI-FDP)in the diagnosis of early breast cancer with non-calcified.Methods A total of 95 cases patients with early breast cancer with non-calcified(the longest diameter of the lesion≤2 cm,regardless of the size of the carcinoma in situ)were retrospectively included.Clinical,pathological and imaging data of all patients were collected.All patients underwent FFDM and MRI scanning,and three examination regimens,including FFDM,BMRI-AP,BMRI-FDP,were further obtained.Classification was performed according to the breast imaging reporting and data system(BI-RADS)classification standard(fifth edition)developed by American College of Radiology(ACR),and pathological results were taken as the standard.The diagnostic efficacy for early breast cancer with non-calcified were compared among the different three imaging methods.Results The diagnostic accuracy of FFDM,BMRI-AP and BMRI-FDP for early breast cancer with non-calcified was 76.84%,93.68%and 95.79%,respectively,with statistically significant difference among three groups(χ2=20.558,P<0.001).The median(quartile distance)of BMRI-AP and BMRI-FDP scanning time were 478(5)s and 926(13)s,respectively,with statistically significant difference between the two groups(Z=-11.912,P<0.001).Conclusion The diagnostic accuracy of BMRI-AP is significantly better than that of FFDM and similar to that of BMRI-FDP for early breast cancer with non-calcified.In addition,BMRI-AP can significantly shorten the scanning time without reducing the diagnostic accuracy,which is expected to become a new breast cancer screening method.

Objective:To summarize the best evidence for exercise intervention in elderly patients with sarcopenia in intensive care unit (ICU) through literature search, and provide a reference for clinical implementation of early exercise intervention in this population through evidence-based practice.Methods:① Summary of best evidence: relevant literature on exercise intervention for elderly patients with sarcopenia in ICU, including guideline, evidence summary, expert consensus, systematic review, and original study [quasi-experiment and randomized controlled trial (RCT)] from UpToDate Clinical Advisor, Ovid database, National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed/Medline, SinoMed, CNKI, Wanfang Database, VIP, and Yimai Tong Guideline Network were systematically searched. The search period covered from the establishment of these databases up to August 24, 2023. The quality of the literature was evaluated by two researchers with methodological expertise in evidence-based medicine, and the evidences were extracted and summarized. ② Evidence-based practice: the elderly patients with high risk of sarcopenia who had been hospitalized in the ICU for more than 7 days from January to April 2024 were enrolled as the research subjects, and they were divided into a control group and an intervention group using convenience sampling method. The control group received routine intensive care nursing. The intervention group implemented exercise intervention based on the actual situation of the patients, the baseline review was conducted before evidence application, and the effectiveness of evidence application at 7 days and 14 days was evaluated.Results:① A total of 19 pieces of literature were included, including 4 guidelines, 1 summary of evidence, 4 expert consensuses, 4 systematic reviews, and 6 original studies (1 quasi-experiment, 5 RCT). After literature quality evaluation, all 19 articles were enrolled. Finally, 31 pieces of best evidence were extracted from eight aspects, including assessment and diagnosis, multidisciplinary cooperation, indication, preparation before intervention, intervention program, safety monitoring, post-intervention evaluation, and special task. ② Finally, a total of 30 patients were enrolled in the intervention group, of which 17 completed 14 days of rehabilitation exercise, and 13 completed 7 days of rehabilitation exercise. Twenty-seven patients were enrolled in the control group, of which 17 completed 14 days of monitoring, and 10 completed 7 days of monitoring. Clinical evidence application results showed that the patients in the intervention group did not experience adverse events such as increased heart rate, extubation, or physical discomfort. The skeletal muscle mass index (SMI) in both groups was gradually decreased with the prolongation of intervention duration, but the 7-day SMI in the intervention group was significantly higher than that in the control group (kg/m 2: 8.61±2.66 vs. 6.65±1.50, P < 0.01). Conclusion:By summarizing the best evidence and evidence-based practice of exercise intervention for elderly patients with sarcopenia in ICU, this study confirmed the feasibility due to safe and effective of implementing early exercise intervention for elderly sarcopenia patients in ICU.

Objective:To investigate and analysis of the occurrence and influencing factors of sarcopenia in elderly critically ill patients in the intensive care unit (ICU).Methods:A prospective cohort study was conducted. Elderly patients (aged ≥ 60 years) admitted to the ICU of Tianjin Medical University General Hospital from November 2023 to June 2024 were enrolled. Clinical records were collected, and conduct muscle mass and strength measurements, as well as upper arm circumference and calf circumference were measured. Appendicular skeletal muscle index (ASMI) of less than 7.0 kg/m 2 for males and less than 5.7 kg/m 2 for females was defined as reduced muscle mass, grip strength of less than 28 kg for males and less than 18 kg for females was defined as decreased muscle strength, patients meeting both low muscle mass and low muscle strength criteria were diagnosed with sarcopenia. According to the diagnostic criteria for sarcopenia, patients were divided into sarcopenia group and non-sarcopenia group. Multivariate Logistic regression analysis was applied to identify risk factors for sarcopenia in the elderly and to develop a predictive model for the occurrence of sarcopenia. The predictive value of various risk factors for sarcopenia in elderly critically ill patients were evaluated by receiver operator characteristic curve (ROC curve). The Kaplan-Meier curve for the length of ICU stay of two groups patients were drawn. Results:Finally, 540 elderly critically ill patients were included, including 43 patients with sarcopenia, and the incidence of sarcopenia was 8.0%. Univariate analysis showed that there were significantly differences in body mass index (BMI), number of hospitalizations in the past year, the length of ICU stay, ventilation mode, duration of mechanical ventilation, pre-admission exercise habits, nutritional support methods, upper arm circumference, calf circumference, and albumin infusion between the sarcopenia group and the non-sarcopenia group. Multivariate Logistic regression analysis showed that BMI [odds ratio ( OR) = 0.79, 95% confidence interval (95% CI) was 0.67-0.93, P = 0.004], calf circumference ( OR = 0.64, 95% CI was 0.54-0.76, P < 0.001), and duration of mechanical ventilation ( OR = 1.06, 95% CI was 1.01-1.12, P = 0.034) were associated with an increased risk of sarcopenia in elderly critically ill patients. The ROC curve results showed that the area under the curve (AUC) and 95% CI of BMI, calf circumference, and duration of mechanical ventilation for predicting sarcopenia in elderly critically ill patients were 0.828 (0.767-0.888), 0.889 (0.844-0.933), and 0.397 (0.299-0.496), respectively, with cut-off values of 22.95 kg/m 2, 28.25 cm, and 50.50 days, respectively. The Kaplan-Meier curve showed that the cumulative survival rate of patients with sarcopenia was significantly lower than that of the non-sarcopenia group (Log-Rank test: χ 2 = 5.619, P = 0.018). Conclusion:Lower BMI, smaller calf circumference, and longer duration of mechanical ventilation are associated with an increased risk of sarcopenia in critically ill elderly patients.

Objective·To establish a mouse model with dormant cancer and no obvious metastasis by combining the preimmune strategy with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.Methods·The KPC1199 mouse pancreatic cancer cell line was transfected with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system to construct a stable expression cell line,KPC1199-PDL.After being cultured in the serum-free condition,KPC1199-PDL cells were sorted into mVenus(+)cells and mVenus(-)cells by flow cytometry,and the expression of G0 phase-related genes was verified by real-time fluorescence quantitative PCR(qPCR).Sensitivity of KPC1199-PDL cells to diphtheria toxin(DTX)and ganciclovir(GCV)was evaluated by CCK-8 assay.A transsplenic portal vein-hepatic metastasis model was constructed in wild-type C57BL/6 mice to validate the function of KPC1199-PDL cells in vivo by immunofluorescence technology.The KPC1199-PDL cells were injected subcutaneously into C57BL/6 mice,followed by in situ injection of DTX and GCV to ablate subcutaneous tumors 5 d later,to obtain preimmunized mice.The transsplenic portal vein-hepatic metastasis models were constructed in these mice.Bioluminescence imaging was used to evaluate subcutaneous tumor ablation and hepatic metastasis in the mice,and immunofluorescence assay was used to detect the distribution and dormant state of tumor cells in the livers of preimmunize mice.Results·The three tool systems were stably expressed in KPC1199-PDL cells,and their proliferative ability was not affected.In the serum starving condition,some KPC1199-PDL cells expressed the mVenus protein,indicating entry into the G0 phase;the mVenus(+)cells sorted out by flow cytometry exhibited significantly higher expression of G0 phase-related genes(all P<0.05)and significantly lower expression of the proliferation-related gene compared with mVenus(-)cells(P<0.05).The CCK-8 assay demonstrated high sensitivity of KPC1199-PDL cells to DTX and GCV.In vivo experiments confirmed that KPC1199-PDL cells could be effectively traced through tdTomato protein expression,and could indicate entry into the G0 phase through mVenus protein expression.Following subcutaneous tumor implantation and drug ablation,preimmunized mice were successfully obtained.In the subsequent transsplenic portal vein-hepatic metastasis model,no metastatic signals were observed in the liver by bioluminescence imaging,but single or small clusters of G0 phase tumor cells expressing both mVenus and tdTomato,not expressing the proliferation marker Ki67,were detected in liver tissue sections by immunofluorescence analysis.Conclusions·A recognizable and traceable dormant cancer model is constructed with the combination of the preimmune mouse model of pancreatic cancer,the mVeneus-p27K-indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.