Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Objective:To investigate the feasibility of ultra-low dose (ULD) CT pulmonary angiography (CTPA) combined with deep learning reconstruction (DLR) in the diagnosis of pulmonary embolism (PE).Methods:This cross-sectional study prospectively enrolled 100 patients with suspected PE who underwent CTPA examination in Zhongshan Hospital Fudan University, and Shanghai Geriatric Medical Center from April to July 2024, and were randomly divided into the routine dose (RD) group and ULD group according to block randomization. Effective dose (ED) were calculated. The noise index of RD group and ULD group was set to 10 and 20, respectively. Other scanning parameters and contrast agent injection protocol were the same. The CT images of RD group were reconstructed using hybrid iterative reconstruction (HIR), while ULD images were reconstructed with HIR and DLR (ULD-HIR subgroup and ULD-DLR subgroup). The image quality of the three groups of images was subjectively evaluated (overall image noise, pulmonary artery display) and objectively evaluated [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of the images] respectively. Finally, the diagnostic results of PE by the expert committee composed of three chief physicians were taken as the gold standard, and one physician with lower qualifications independently evaluated the diagnostic rate of PE in the three groups of images. Objective image quality parameters across the three groups were compared using ANOVA, with LSD post hoc test was used for multiple comparisons. Subjective scores among the three groups were analyzed using the Kruskal-Wallis H test, with Bonferroni corrected pairwise post hoc test was applied for multiple pairwise comparisons. Results:The ED in the RD group and ULD group were (2.7±0.5) mSv and (0.7±0.2) mSv, respectively, and the differences were statistically significant ( t=26.42, P<0.001). The overall differences in CT values of pulmonary arteries at all levels in the images of the RD group, the ULD-HIR subgroup, and the ULD-DLR subgroup were not statistically significant ( P>0.05).The RD group, ULD-HIR subgroup and ULD-DLR subgroup overall differences in SNR and CNR at all levels pulmonary arteries were statistically significant ( P<0.001), in which except for the differences in CNR and SNR values of the left pulmonary arterial trunk in the RD group and the ULD-HIR subgroup, and SNR values of basal segment pulmonary artery of the lower lobe of the left lung, which were not statistically significant ( P>0.05), the differences of the rest of the indexes in the pairwise comparisons between the groups were statistically significant ( P<0.05). The overall differences in the subjective scores of image pulmonary vascular display and image noise in the RD group, ULD-HIR subgroup and ULD-DLR subgroup were statistically significant ( P<0.001), except that the differences in the subjective scores of image pulmonary vascular display in the ULD-DLR subgroup were not statistically significant when compared with that of the RD group ( P>0.05) and that of the rest of the metrics in the between-groups two-by-two comparisons were all statistically significant ( P<0.05). The difference in diagnostic rates of PE in the pulmonary artery trunk, lobe and segmental levels in the images of the RD group, ULD-HIR subgroup and ULD-DLR subgroup was not statistically significant ( P>0.05). Conclusions:DLR can significantly reduce the radiation dose of CTPA examination. Even at ultra-low radiation dose, its image quality is still better than HIR reconstruction at conventional doses and preserve diagnostic accuracy of PE at the lobe level and segment level.

Objective To investigate the value of flexible subtraction CE-Boost technique combined with low dosage contrast agents for CT pulmonary angiography(CTPA).Methods A total of 68 patients who would undergo CTPA examination due to suspected pulmonary embolism(PE)were prospectively enrolled and randomly divided into study group(n=34)and control group(n=34)using block randomization method.After injecting 25 ml contrast agents at a flow rate of 2.5 ml/s in study group or 50 ml contrast agents at a flow rate of 3.5 ml/s in control group,CTPA scanning were performed with identical parameters.For images in study group,hybrid iterative reconstruction was performed,followed by flexible subtraction CE-Boost post-processing to obtain CE-Boost CTPA.For images in control group,conventional CTPA was obtained with hybrid iterative reconstruction.Subjective and objective evaluations of image quality were compared between groups.Taken the final clinical diagnosis as standard,the accuracy rate of diagnosing PE were compared between groups.Results There were 7 cases of pulmonary artery main trunk PE and 15 cases of pulmonary lobe-level PE in study group,while in control group there were 8 cases and 17 cases.No statistical difference of subjective scores of CTPA was found between groups(P＞0.05).CT values of the main pulmonary artery,bilateral pulmonary artery trunks and lower lobes of both lungs,signal-to-noise ratio or contrast-to-noise ratio in CTPA were not significantly different between groups(all P＞0.05),while no significant difference of the accuracy rate of CTPA for diagnosing PE of pulmonary artery main trunk(100％[7/7]vs.100％[8/8])nor pulmonary lobe-level PE(86.67％[13/15]vs.88.24％[15/17])was detected between groups(all P＞0.05).Conclusion Flexible subtraction CE-Boost technique combined with low dosage contrast agents for CTPA could reduce contrast agent dosage without affecting image quality.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Objective:To investigate the feasibility of ultra-low dose (ULD) CT pulmonary angiography (CTPA) combined with deep learning reconstruction (DLR) in the diagnosis of pulmonary embolism (PE).Methods:This cross-sectional study prospectively enrolled 100 patients with suspected PE who underwent CTPA examination in Zhongshan Hospital Fudan University, and Shanghai Geriatric Medical Center from April to July 2024, and were randomly divided into the routine dose (RD) group and ULD group according to block randomization. Effective dose (ED) were calculated. The noise index of RD group and ULD group was set to 10 and 20, respectively. Other scanning parameters and contrast agent injection protocol were the same. The CT images of RD group were reconstructed using hybrid iterative reconstruction (HIR), while ULD images were reconstructed with HIR and DLR (ULD-HIR subgroup and ULD-DLR subgroup). The image quality of the three groups of images was subjectively evaluated (overall image noise, pulmonary artery display) and objectively evaluated [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of the images] respectively. Finally, the diagnostic results of PE by the expert committee composed of three chief physicians were taken as the gold standard, and one physician with lower qualifications independently evaluated the diagnostic rate of PE in the three groups of images. Objective image quality parameters across the three groups were compared using ANOVA, with LSD post hoc test was used for multiple comparisons. Subjective scores among the three groups were analyzed using the Kruskal-Wallis H test, with Bonferroni corrected pairwise post hoc test was applied for multiple pairwise comparisons. Results:The ED in the RD group and ULD group were (2.7±0.5) mSv and (0.7±0.2) mSv, respectively, and the differences were statistically significant ( t=26.42, P<0.001). The overall differences in CT values of pulmonary arteries at all levels in the images of the RD group, the ULD-HIR subgroup, and the ULD-DLR subgroup were not statistically significant ( P>0.05).The RD group, ULD-HIR subgroup and ULD-DLR subgroup overall differences in SNR and CNR at all levels pulmonary arteries were statistically significant ( P<0.001), in which except for the differences in CNR and SNR values of the left pulmonary arterial trunk in the RD group and the ULD-HIR subgroup, and SNR values of basal segment pulmonary artery of the lower lobe of the left lung, which were not statistically significant ( P>0.05), the differences of the rest of the indexes in the pairwise comparisons between the groups were statistically significant ( P<0.05). The overall differences in the subjective scores of image pulmonary vascular display and image noise in the RD group, ULD-HIR subgroup and ULD-DLR subgroup were statistically significant ( P<0.001), except that the differences in the subjective scores of image pulmonary vascular display in the ULD-DLR subgroup were not statistically significant when compared with that of the RD group ( P>0.05) and that of the rest of the metrics in the between-groups two-by-two comparisons were all statistically significant ( P<0.05). The difference in diagnostic rates of PE in the pulmonary artery trunk, lobe and segmental levels in the images of the RD group, ULD-HIR subgroup and ULD-DLR subgroup was not statistically significant ( P>0.05). Conclusions:DLR can significantly reduce the radiation dose of CTPA examination. Even at ultra-low radiation dose, its image quality is still better than HIR reconstruction at conventional doses and preserve diagnostic accuracy of PE at the lobe level and segment level.

Objective To investigate the value of flexible subtraction CE-Boost technique combined with low dosage contrast agents for CT pulmonary angiography(CTPA).Methods A total of 68 patients who would undergo CTPA examination due to suspected pulmonary embolism(PE)were prospectively enrolled and randomly divided into study group(n=34)and control group(n=34)using block randomization method.After injecting 25 ml contrast agents at a flow rate of 2.5 ml/s in study group or 50 ml contrast agents at a flow rate of 3.5 ml/s in control group,CTPA scanning were performed with identical parameters.For images in study group,hybrid iterative reconstruction was performed,followed by flexible subtraction CE-Boost post-processing to obtain CE-Boost CTPA.For images in control group,conventional CTPA was obtained with hybrid iterative reconstruction.Subjective and objective evaluations of image quality were compared between groups.Taken the final clinical diagnosis as standard,the accuracy rate of diagnosing PE were compared between groups.Results There were 7 cases of pulmonary artery main trunk PE and 15 cases of pulmonary lobe-level PE in study group,while in control group there were 8 cases and 17 cases.No statistical difference of subjective scores of CTPA was found between groups(P＞0.05).CT values of the main pulmonary artery,bilateral pulmonary artery trunks and lower lobes of both lungs,signal-to-noise ratio or contrast-to-noise ratio in CTPA were not significantly different between groups(all P＞0.05),while no significant difference of the accuracy rate of CTPA for diagnosing PE of pulmonary artery main trunk(100％[7/7]vs.100％[8/8])nor pulmonary lobe-level PE(86.67％[13/15]vs.88.24％[15/17])was detected between groups(all P＞0.05).Conclusion Flexible subtraction CE-Boost technique combined with low dosage contrast agents for CTPA could reduce contrast agent dosage without affecting image quality.

ObjectiveTo systematically compare the chemical compositional differences between Puerariae Thomsonii stem base（PTSB） and Puerariae Thomsonii Radix（PTR）， and to explore the potential hepatoprotective effects of PTSB by liver metabolomics. MethodUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to analyze the chemical compositions of PTSB and PTR. Twenty Kunming mice aged 6-8 weeks， half male and half female， were randomly divided into the blank group（sterile water） and PTSB group（1.95 g·kg^-1）， with 10 mice in each group， and the drug was administered by gavage for 14 d， and the body mass was weighed once a day. After the last administration， mice were anesthetized， organs such as heart， liver， spleen， lungs and kidneys were collected， and the organ index was calculated. Enzyme-linked immunosorbent assay（ELISA） was used to measure the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， total cholesterol（TC） and triglyceride（TG） in the serum of mice from each group， the morphological changes of heart， liver， spleen， lung and kidney tissues were observed by hematoxylin-eosin（HE） staining， and the regulation of PTSB for the hepatic metabolic profiles of mice was analyzed by UPLC-Q-TOF-MS/MS， then the differential metabolites between the blank group and PTSB group were designated， and the metabolic pathways was enriched by Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultA total of 19 common chemical constituents were identified from PTSB and PTR， all of which were the main pharmacodynamic substances of PTR. The pharmacodynamic results showed that PTSB could control the growth of body mass of mice and reduce the contents of TC， TG， ALT and AST in serum of mice. HE staining observations and organ indexes showed that there was no significant effect of PTSB on all major organs at the highest clinically equivalent dose. A total of 38 differential metabolites were identified by metabolomics， of which 35 were up-regulated and 3 were down-regulated. These differential metabolites were mainly compounds such as amino acids， fatty acids， vitamins， steroids， nucleosides， pyrimidines and alkaloids. Three key metabolic pathways， including tyrosine metabolism， vitamin B₆ metabolism and tryptophan metabolism， were screened by metabolic pathway analysis. ConclusionPTSB has a similar chemical composition to that of PTR， and it may regulate the metabolism of amino acids and vitamins through the flavonoids and isoflavonoids， thus exerting a potential hepatoprotective effect. This study provides an experimental reference for the clinical application and product development of PTSB.