OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Gastrointestinal (GI) cancers are prevalent globally, with leading incidence and mortality rates among malignant tumors. Despite notable advancements in surgical resection, radiotherapy, and chemotherapy, the overall survival rates remain low. Hence, it is imperative to explore alternative approaches that enhance patient outcomes. Cluster of differentiation 47 (CD47), serving as an early diagnostic marker, is predominantly overexpressed in GI cancers and associated with poor prognosis. Targeting the CD47-signal regulatory protein alpha (SIRPα) signaling pathway may provide a novel strategy for GI cancers treatment. This study summarizes current knowledge of the structure and function of CD47 and SIRPα, their roles in signaling pathways, the prognostic significance of CD47, therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer, and highlights key issues for future investigations.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective To investigate the effects and mechanisms of high-fat diet(HFD)-induced obesity on male ze-brafish reproductive function.Methods Adult male zebrafish were divided into normal diet(ND)group and HFD group.Growth and metabolic conditions were evaluated by measuring body weight,body length,BMI,organ index,and glucose/lipid lev-els.Reproductive capacity was assessed via sperm concentration,motility,fertilization rate,and testosterone levels.Testicular tissues from both of groups were subjected to transeriptomic sequencing(RNA-seq).And qRT-PCR was used to validate the expression of genes.Results Compared to male zebrafish in ND group,the ones in HFD group exhibited hepatic steatosis and glucose/lipid meta-bolic disorders(P＜0.05).Testicular structural disorganization,along with reduced testosterone levels,decreased gonadosomatic in-dex,and impaired sperm concentration and motility occurred in HFD group(P＜0.05).GO analysis revealed that differentially ex-pressed genes were enriched in spermatogenesis and ciliary system,while KEGG analysis highlighted metabolic related pathways(pu-rine metabolism,thyroid hormone synthesis,mTOR signaling)and cell adhesion molecules.Twenty key differentially expressed genes were validated by qRT-PCR,which confirmed the reliability of RNA-Seq results.Conclusion Impairment of reproductive function induced by HFD in zebrafish may be associated with three regulatory mechanisms including ciliary system,metabolic dysregulation,and aberrant cell adhesion molecule signaling.This study provides mechanistic insights and identifies potential therapeutic targets for clinical management of diet-associated infertility.

Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPα)signaling pathway may provide a novel strategy for GI cancers treatment This study summarizes current knowledge of the structure and function of CD47 and SIRPα,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective:To compare the medical costs of using standard fortified donor human milk (DHM) or preterm formula (PF) to supply very low birth weight [VLBW, defined as birth weight (BW) ≥1 000 g but <1 500 g] and extremely low birth weight (ELBW, defined as BW <1 000 g) premature infants with insufficient maternal breast milk.Methods:VLBW and ELBW preterm infants hospitalized in Peking Union Medical College Hospital from September 2017 to October 2020 were retrospectively enrolled and assigned into DHM group and PF group based on complementary feeding methods. The cost of parenteral nutrition (PN), cost of antibiotics, and total medical expenses during hospitalization were compared between the two groups.Results:A total of 89 infants were enrolled in this study, out of whom 50 was in the DHM group and 39 the PF group. The gestational age in DHM group and PF group were both (29±2) weeks. The BW of DHM group was 1 170 (919, 1 380)?g and that of PF group was 1 170 (1 010, 1 360) g. There were no significant differences in gestational age, BW, maternal age at delivery, delivery mode, gender ratio, proportion of small-for-gestational-age infants and length of hospital stay between the two groups (all P>0.05). The cost of parenteral nutrition in DHM group was significantly lower than that in PF group [3 500 (1 922, 5 704) Chinese yuan vs 7 995 (5 579, 10 788) Chinese Yuan, P<0.01]. The cost of antibiotics in DHM group was significantly lower than that in PF group [6 529 (2 265, 10 860) Chinese Yuan vs 13 676 (10 480, 18 506) Chinese Yuan, P<0.01]. The difference in total medical expense during hospitalization showed no statistical significance between two groups ( P>0.05). Amorg VLBW preterm infants, the cost of PN, cost of antibiotics, total cost of hospitalization, and daily cost of hospitalization in HDM group was significantly lower than that in PF group (all P<0.05). In ELBW preterm infants, the cost of PN and the cost of antibiotics in HDM group were significantly lower than that in PF group (both P<0.05), but the total cost of hospitalization and the daily cost of hospitalization between two groups showed no significant difference (all P>0.05). Conclusions:When mother's own milk is insufficient, using donor human milk reduces the costs of PN and antibiotics in VLBW and ELBW preterm infants compared with using PF. In VLBW preterm infants, using DHM can also reduce the total and daily cost of hospitalization.

This study was aimed at investigating the presence of Helicobacter hepaticus(Hh)infection in patients with digestive tract diseases and evaluating Helicobacter pylori(Hp)infection status in patients with digestive tract cancers other than gastric cancer.Fecal samples were collected from 197 patients with digestive tract diseases at the Affiliated Cancer Hospital of Guizhou Medical Uni-versity and from 149 healthy volunteers residing in Guiyang.Hp stool antigen(HpSA)was detected with the colloidal gold method.Af-ter the extraction of fecal DNA,the Hp specific ureA gene and the Hh specific 16S rRNA gene were amplified via nested PCR,and the amplified products were subsequently confirmed through sequencing analysis.The study included 197 patients with digestive system diseases,comprising 135 cases of colorectal cancer,32 cases of chronic gastritis,22 cases of gastric cancer,5 cases of liver cancer,and 3 cases of cholangiocarcinoma.The detection rate of HpSA was 31.5%(62/197).HpSA was detected across all five disease catego-ries,and the highest detection rate was observed in patients with gastric cancer,at 50.0%(11/22),or colorectal cancer,at 24.4%(33/135).The positivity rate of Hp ureA gene PCR was 7.6%(15/197),and sequencing confirmed that the amplified products were in-deed Hp ureA gene fragments.Notably,the highest detection rate was observed in patients with colorectal cancer,at 8.9%(12/135).The positivity rate of Hh 16S rRNA gene PCR was 11.2%(22/197),and sequencing confirmed that the amplified products were in-deed Hh 16S rRNA gene fragments.Hh 16S rRNAgene presence was detected in patients with all five diseases,and the highest detec-tion rate was observed in patients with colorectal cancer,at 11.1%(15/135).Among 149 healthy volunteers,the detection rate of HpSA was 11.4%(17/149),only one case tested positive for the Hp ureA gene,and the Hh 16S rRNA gene was undetectable in all samples.In conclusion,Hh infection was detected in patients with digestive tract diseases.Beyond patients with gastric cancer,the prevalence of Hp infection was also notably high among patients with colorectal cancer,liver cancer,and cholangiocarcinoma.Further investigation is warranted to elucidate the roles of the two species of Helicobacter in the occurrence and progression of digestive tract cancers.

Objective:To compare the medical costs of using standard fortified donor human milk (DHM) or preterm formula (PF) to supply very low birth weight [VLBW, defined as birth weight (BW) ≥1 000 g but <1 500 g] and extremely low birth weight (ELBW, defined as BW <1 000 g) premature infants with insufficient maternal breast milk.Methods:VLBW and ELBW preterm infants hospitalized in Peking Union Medical College Hospital from September 2017 to October 2020 were retrospectively enrolled and assigned into DHM group and PF group based on complementary feeding methods. The cost of parenteral nutrition (PN), cost of antibiotics, and total medical expenses during hospitalization were compared between the two groups.Results:A total of 89 infants were enrolled in this study, out of whom 50 was in the DHM group and 39 the PF group. The gestational age in DHM group and PF group were both (29±2) weeks. The BW of DHM group was 1 170 (919, 1 380)?g and that of PF group was 1 170 (1 010, 1 360) g. There were no significant differences in gestational age, BW, maternal age at delivery, delivery mode, gender ratio, proportion of small-for-gestational-age infants and length of hospital stay between the two groups (all P>0.05). The cost of parenteral nutrition in DHM group was significantly lower than that in PF group [3 500 (1 922, 5 704) Chinese yuan vs 7 995 (5 579, 10 788) Chinese Yuan, P<0.01]. The cost of antibiotics in DHM group was significantly lower than that in PF group [6 529 (2 265, 10 860) Chinese Yuan vs 13 676 (10 480, 18 506) Chinese Yuan, P<0.01]. The difference in total medical expense during hospitalization showed no statistical significance between two groups ( P>0.05). Amorg VLBW preterm infants, the cost of PN, cost of antibiotics, total cost of hospitalization, and daily cost of hospitalization in HDM group was significantly lower than that in PF group (all P<0.05). In ELBW preterm infants, the cost of PN and the cost of antibiotics in HDM group were significantly lower than that in PF group (both P<0.05), but the total cost of hospitalization and the daily cost of hospitalization between two groups showed no significant difference (all P>0.05). Conclusions:When mother's own milk is insufficient, using donor human milk reduces the costs of PN and antibiotics in VLBW and ELBW preterm infants compared with using PF. In VLBW preterm infants, using DHM can also reduce the total and daily cost of hospitalization.