Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Objective:To investigate the efficacy of posterior cranial fossa in- situ floating bone flap osteotomy in the treatment of syndromic craniosynostosis(SCS). Methods:The clinical data of SCS children who underwent posterior cranial fossa in- situ floating bone flap osteotomy at the Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine from April 2020 to August 2022 were retrospectively analyzed. The surgical procedures were as follows. The occipital bone was cut into several mosaic bone flaps of varying sizes, without peeling it off the dura, which were left as a small free floating bone flap. The anteroposterior cranial diameter, cranial height, intracranial volume, and degree of improvement in tonsillar herniation and hydrocephalus of the children (hydrocephalus quantification was performed using the ratio of the ventricular diameter to the biparietal diameter)were measured preoperatively, 7 days postoperatively, 3 months postoperatively, and at the last follow-up (at least 12 months after the operation) to evaluate the surgical outcomes. The measurement data of normal distribution were expressed as Mean±SD. The paired t-test was used for comparison within the repeated measurement data groups at the two time points. One-way repeated measures analysis of variance (ANOVA) was performed on the repeated measurement data at multiple time points, and pairwise comparisons in post hoc tests were corrected using the Bonferroni method. Results:A total of 17 pediatric patients with SCS were included, comprising 10 males and 7 females, with ages ranging from 4 to 18 months (mean age: 9.5 months). Among them, 12 patients were complicated with Chiari malformation and hydrocephalus (1 severe case, 8 moderate cases, and 3 mild cases). Postoperative follow-up lasted 12 to 35 months, with an average of 17 months. After surgery, the posterior cranial appearance of the children was enlarged, with increased convexity of the occiput and a full contour. At the last follow-up, the middle cranial height [(107.80±10.72) mm vs. (102.82±10.09) mm, P<0.05], the posterior cranial height [(124.91±10.40) mm vs. (107.58±13.46) mm, P<0.01] and anteroposterior diameter [(153.30±11.26) mm vs. (123.64±17.44) mm, P<0.01] as well as the intracranial volume [(1 317.92±225.77) cm 3 vs. (1 014.93±231.81) cm 3,P<0.01] were increased compared with the preoperative period, and the average improvement rate of intracranial volume was 37.0% (18.1%-79.2%). Among the 12 cases of tonsillar herniation, 7 cases had improvement. Moreover, all the 12 cases of hydrocephalus witnessed a mitigation in severity, from (46.33±9.34)% preoperatively to (35.24±9.88)% postoperatively, with a statistically significant difference ( P<0.01). Conclusion:Posterior cranial fossa in- situ floating bone flap osteotomy can effectively improve the appearance of patients with SCS, increase the intracranial volume, relieve the degree of hydrocephalus, and reduce the intracranial pressure.

The mother formula of Ruyizhenbao formula was the 25-flavor Zhumu Fang recorded in the Four Medical Codes,which was called Ruyi 25-flavor Zhumu Fang in the 16th century book Tibetan Medicine Ruyi Daquan.Later,in the book Qianwan Sheli,licorice was added to the formula,forming a 26-flavor basic formula of Ruyizhenbao.With the development of Tibetan medicine history,various doctors added and subtracted medicinal flavors to the basic formula.Finally,it was developed by Qinrenorbu into Ruyizhenbao formula composed of 30 herbs,which was published in the Treasure Source of Tibetan Medicine Secrets and was included in the Drug Standard of the Ministry of Health(Tibetan medicine)in 1995,becoming the formula standard of Ruyizhenbao formula.Through systematically sorting out Tibetan medicine literature from past dynasties,the formula name,medicinal taste composition,and changes of Ruyizhenbao formula recorded in different literature was comprehensively analyzed.Through primary literature research,the various claims about the origin of Ruyizhenbao formula published to date have been verified one by one to clarify its past and present,and to clarify its origin.The mother formula of Ruyizhenbao is the 25-flavor mother powder recorded in the Four Medical Codes.The basic formula is the Ruyizhenbao formula composed of 26 herbs in Qianwan Sheli,and the standard formula is the Ruyizhenbao formula composed of 30 herbs in the Treasure Source of Tibetan Medicine Secrets.

The mother formula of Ruyizhenbao formula was the 25-flavor Zhumu Fang recorded in the Four Medical Codes,which was called Ruyi 25-flavor Zhumu Fang in the 16th century book Tibetan Medicine Ruyi Daquan.Later,in the book Qianwan Sheli,licorice was added to the formula,forming a 26-flavor basic formula of Ruyizhenbao.With the development of Tibetan medicine history,various doctors added and subtracted medicinal flavors to the basic formula.Finally,it was developed by Qinrenorbu into Ruyizhenbao formula composed of 30 herbs,which was published in the Treasure Source of Tibetan Medicine Secrets and was included in the Drug Standard of the Ministry of Health(Tibetan medicine)in 1995,becoming the formula standard of Ruyizhenbao formula.Through systematically sorting out Tibetan medicine literature from past dynasties,the formula name,medicinal taste composition,and changes of Ruyizhenbao formula recorded in different literature was comprehensively analyzed.Through primary literature research,the various claims about the origin of Ruyizhenbao formula published to date have been verified one by one to clarify its past and present,and to clarify its origin.The mother formula of Ruyizhenbao is the 25-flavor mother powder recorded in the Four Medical Codes.The basic formula is the Ruyizhenbao formula composed of 26 herbs in Qianwan Sheli,and the standard formula is the Ruyizhenbao formula composed of 30 herbs in the Treasure Source of Tibetan Medicine Secrets.

Objective:To investigate the efficacy of posterior cranial fossa in- situ floating bone flap osteotomy in the treatment of syndromic craniosynostosis(SCS). Methods:The clinical data of SCS children who underwent posterior cranial fossa in- situ floating bone flap osteotomy at the Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine from April 2020 to August 2022 were retrospectively analyzed. The surgical procedures were as follows. The occipital bone was cut into several mosaic bone flaps of varying sizes, without peeling it off the dura, which were left as a small free floating bone flap. The anteroposterior cranial diameter, cranial height, intracranial volume, and degree of improvement in tonsillar herniation and hydrocephalus of the children (hydrocephalus quantification was performed using the ratio of the ventricular diameter to the biparietal diameter)were measured preoperatively, 7 days postoperatively, 3 months postoperatively, and at the last follow-up (at least 12 months after the operation) to evaluate the surgical outcomes. The measurement data of normal distribution were expressed as Mean±SD. The paired t-test was used for comparison within the repeated measurement data groups at the two time points. One-way repeated measures analysis of variance (ANOVA) was performed on the repeated measurement data at multiple time points, and pairwise comparisons in post hoc tests were corrected using the Bonferroni method. Results:A total of 17 pediatric patients with SCS were included, comprising 10 males and 7 females, with ages ranging from 4 to 18 months (mean age: 9.5 months). Among them, 12 patients were complicated with Chiari malformation and hydrocephalus (1 severe case, 8 moderate cases, and 3 mild cases). Postoperative follow-up lasted 12 to 35 months, with an average of 17 months. After surgery, the posterior cranial appearance of the children was enlarged, with increased convexity of the occiput and a full contour. At the last follow-up, the middle cranial height [(107.80±10.72) mm vs. (102.82±10.09) mm, P<0.05], the posterior cranial height [(124.91±10.40) mm vs. (107.58±13.46) mm, P<0.01] and anteroposterior diameter [(153.30±11.26) mm vs. (123.64±17.44) mm, P<0.01] as well as the intracranial volume [(1 317.92±225.77) cm 3 vs. (1 014.93±231.81) cm 3,P<0.01] were increased compared with the preoperative period, and the average improvement rate of intracranial volume was 37.0% (18.1%-79.2%). Among the 12 cases of tonsillar herniation, 7 cases had improvement. Moreover, all the 12 cases of hydrocephalus witnessed a mitigation in severity, from (46.33±9.34)% preoperatively to (35.24±9.88)% postoperatively, with a statistically significant difference ( P<0.01). Conclusion:Posterior cranial fossa in- situ floating bone flap osteotomy can effectively improve the appearance of patients with SCS, increase the intracranial volume, relieve the degree of hydrocephalus, and reduce the intracranial pressure.

Objective To construct hepatocyte-specific silence information regulator 3(Sirt3)gene knockout(Sirt3 Δhep)mice by Cre-loxP technique,and to provide an important animal model for further studying the biological function of the hepatocyte Sirt3 gene in diseases.Methods LoxP-labeled Sirt3flox/flox mice were mated with Alb-Cre homozygous(Alb-Cre+/+)mice,and the F1 generation Sirt3flox/-/Alb-Cre+/-mice were then mated with Sirt3flox/flox mice,and the F2 genotype of Sirt3flox/flox/Alb-Cre+/-mice were the Sirt3 Δhep mice constructed in this ex-periment.Sirt3flox/flox/Alb-Cre-/-(Sirt3flox/flox)mice were the control mice.Mouse tail genome DNA was extracted and PCR was used to identify the genotypes of the offspring mice.Immunofluorescence was used to detect Sirt3 ex-pression in mouse hepatocytes.Primary hepatocytes and tissue proteins of Sirt3 Δhep mice were extracted,and the ex-pression of Sirt3 in mouse hepatocytes and other tissues was verified by Western blot.HE staining was used to ob-serve mice's liver,heart,spleen,and lung tissue structure.Results Sirt3 Δhep mice were successfully identified.Immunofluorescence and Western blot results demonstrated a significant decrease in the expression of Sirt3 in the hepatocytes of these mice compared to the control group(P<0.01).At the same time,there was no significant difference in the expression of Sirt3 in the heart,spleen,kidney,and lung tissues of Sirt3 Δhep mice compared with the control group(P>0.05).The results of HE staining showed that the histological characteristics of the liver,heart,spleen,lungs,kidneys,and other major organs of Sirt3 Δhep mice were not significantly different from those of the control group mice.Conclusion Hepatocyte-specific Sirt3 gene knockout mice are successfully constructed,which provides an animal model to explore further the role and molecular mechanism of the hepatocyte Sirt3 gene in diseases.

Objective:To investigate the agreement of ultrasound derived fat fraction (UDFF) with magnetic resonance imaging proton density fat fraction (MRI PDFF) on evaluating hepatic steatosis, and the performance of UDFF on diagnosing metabolic dysfunction associated steatotic liver disease (MASLD).Methods:One hundred and twenty-five volunteers and one hundred and seven inpatients who underwent abdominal ultrasound examination in Zhongda Hospital Southeast University from November 2023 to February 2024 were prospectively enrolled.UDFF and MRI PDFF were applied to evaluate hepatic steatosis. Spearman correlation test and Bland-Altman plot were applied to analyze the agreement of UDFF and MRI PDFF. Receiver operating characteristic curve (ROC) was applied to calculate the performance of UDFF on diagnosing MASLD.Results:In our participants, compared to individuals without hepatic steatosis, patients with MASLD had higher body mass index (BMI), waist-to-hip ratio, prevalence of diabetes mellitus, levels of alanine transaminase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), triglyceride, and UDFF (all P<0.05). The percentage of hepatic steatosis measured by UDFF and MRI PDFF was strongly correlated[ρ=0.873(95% CI=0.837-0.901), P<0.001]. UDFF performed excellent for diagnosing MASLD with an area under the curve (AUC) of 0.983(95% CI=0.956-0.995, P<0.001), and was better than semi-quantitative assessment based on two-dimensional ultrasound as well as ultrasound attenuation parameter. The optimal cut off value of UDFF to diagnose MASLD was ≥6%. Conclusions:The percentage of hepatic steatosis measured by UDFF and MRI PDFF agrees with each other, and UDFF obtains an excellent performance on diagnosing MASLD, so that UDFF should be considered a reliable imaging technique for quantitively evaluating hepatic steatosis and diagnosing MASLD.

Objective:To retrieve, evaluate and summarize the best evidence of exercise reversal intervention in the elderly with cognitive frailty, and to provide evidence for guiding exercise in elderly patients.Methods:This study was a summary of evidence-based nursing evidence. Based on the PIPOST (P: Population; I: Intervention; P: Professional; O: Outcome; S: Setting; T: Type of evidence) mode, the evidence of exercise reversal intervention in the elderly with cognitive frailty in 25 relevant guideline network and association websites, Chinese and foreign language comprehensive databases such as PubMed, CINAHL, Web of Science, Embase, Chinese Biomedical Database, China National Knowledge Internet and others were searched, extracted and integrated. The retrieval time was from January 1, 2013 to February 14, 2022.Results:A total of 22 articles were included, including 3 guidelines, 2 expert consensuses, 1 clinical decision-making, 1 evidence summary, 9 Meta analysis, and 6 randomized controlled trials. Finally, 28 pieces of the best evidence including 7 dimensions were namely formulate principles,overall assessment, exercise mode, exercise intensity, exercise time and frequency, exercise management, health guidance.Conclusions:This study summarized the best evidence of exercise intervention in the elderly with cognitive frailty, which are systematic, comprehensive, rigorous, and reliable. It can provide references for healthcare administrators to dynamically evaluate patients′cognitive frailty status, formulate personalized exercise programs, and standardize exercise guidance for patients, so as to delay or even reverse cognitive frailty.