OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

AIM:To investigate the effect of drug-containing serum of oxytropis falcata extract on oxi-dative stress injury of podocyte induced by high glucose through PI3K/AKT/Nrf2 pathway.METH-ODS:The rat renal podocyte was cultured in vitro,and the concentration and time of D-glucose mod-elling and the optimal concentration and time of administration in the drug-containing serum of oxy-tropis falcata extract were screened.The cells were divided into normal group,high glucose group,high glucose+blank serum group,oxytropis falcata group,inhibitor group,oxytropis falcata+inhibitor group.Rhodamine staining and electron microsco-py were used to observe the morphological and pathological changes of podocyte,flow cytometry was used to detect apoptosis rate,and cell migra-tion ability was detected by scratch test.Immuno-fluorescence and fluorescence probe were used to detect the fluorescence expression of p-AKT and ROS level of cells,ELISA was used to detect the con-tent of MDA,NO,SOD and T-AOC in the superna-tant of cells,and Western Blot was used to detect the protein expression of p-PI3K/PI3K,p-AKT/AKT and Nrf2 in cells.The mRNA expressions of Nrf2,HO-1,GCLM and SOD were detected by RT-qPCR.RESULTS:It was selected that 45 mmol/LD-glucose induction for 48 hours was the best modeling con-dition,and the 1-fold dilution of the medicated se-rum of oxytropis falcata extract for 48 hours was the best concentration and intervention time.Com-pared with the normal group,the foot processes of the high glucose group were widely fused and ad-hered to each other,the apoptosis rate,migration ability and intracellular ROS level were significantly increased(P＜0.01),the fluorescence expression of p-AKT was markedly decreased(P＜0.01),the con-tents of MDA and NO were dramatically enhanced,and the contents of SOD and T-AOC were signifi-cantly downregulated(P＜0.01).The protein expres-sion of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly declined(P＜0.01).Compared with high glucose group,foot process fusion and adhesion of podo-cytes in oxytropis falcata group and oxytropis falca-ta+inhibitor group were improved in varying de-grees,apoptosis rate,migration ability and intracel-lular ROS level significantly declined(P＜0.05,P＜0.01),p-AKT fluorescence expression increased(P＜0.01),NO content decreased,T-AOC level elevated(P＜0.01);the content of MDA decreased and the activity of SOD notably rose(P＜0.01),the protein expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly increased in oxytropis falcata group(P＜0.05,P＜0.01);the level of ROS in podocytes im-proved(P＜0.01),the fluorescence expression of p-AKT decreased(P＜0.05),the content of NO upregu-lated,the content of T-AOC downregulated,and the expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 pro-tein and HO-1,GCLM,SOD mRNA decreased in in-hibitor group(P＜0.05,P＜0.01).Compared with oxy-tropis falcata group,the apoptosis rate,migration ability and intracellular ROS level of podocytes in oxytropis falcata+inhibitor group markedly in-creased(P＜0.05,P＜0.01),p-AKT fluorescence ex-pression declined(P＜0.01),MDA and NO content increased,SOD and T-AOC content decreased(P＜0.05,P＜0.01),p-PI3K/PI3K,p-AKT/AKT,Nrf2 protein and Nrf2,HO-1,GCLM,SOD mRNA expression all dramatically downregulated(P＜0.05,P＜0.01).CON-CLUSION:Oxytropis falcata extract may protect podocytes by activating the PI3K/AKT/Nrf2 signal-ing pathway,thereby improving the morphological,structural and functional changes of podocytes in-duced by high glucose and inhibiting oxidative stress response.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

AIM:To investigate the effect of drug-containing serum of oxytropis falcata extract on oxi-dative stress injury of podocyte induced by high glucose through PI3K/AKT/Nrf2 pathway.METH-ODS:The rat renal podocyte was cultured in vitro,and the concentration and time of D-glucose mod-elling and the optimal concentration and time of administration in the drug-containing serum of oxy-tropis falcata extract were screened.The cells were divided into normal group,high glucose group,high glucose+blank serum group,oxytropis falcata group,inhibitor group,oxytropis falcata+inhibitor group.Rhodamine staining and electron microsco-py were used to observe the morphological and pathological changes of podocyte,flow cytometry was used to detect apoptosis rate,and cell migra-tion ability was detected by scratch test.Immuno-fluorescence and fluorescence probe were used to detect the fluorescence expression of p-AKT and ROS level of cells,ELISA was used to detect the con-tent of MDA,NO,SOD and T-AOC in the superna-tant of cells,and Western Blot was used to detect the protein expression of p-PI3K/PI3K,p-AKT/AKT and Nrf2 in cells.The mRNA expressions of Nrf2,HO-1,GCLM and SOD were detected by RT-qPCR.RESULTS:It was selected that 45 mmol/LD-glucose induction for 48 hours was the best modeling con-dition,and the 1-fold dilution of the medicated se-rum of oxytropis falcata extract for 48 hours was the best concentration and intervention time.Com-pared with the normal group,the foot processes of the high glucose group were widely fused and ad-hered to each other,the apoptosis rate,migration ability and intracellular ROS level were significantly increased(P＜0.01),the fluorescence expression of p-AKT was markedly decreased(P＜0.01),the con-tents of MDA and NO were dramatically enhanced,and the contents of SOD and T-AOC were signifi-cantly downregulated(P＜0.01).The protein expres-sion of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly declined(P＜0.01).Compared with high glucose group,foot process fusion and adhesion of podo-cytes in oxytropis falcata group and oxytropis falca-ta+inhibitor group were improved in varying de-grees,apoptosis rate,migration ability and intracel-lular ROS level significantly declined(P＜0.05,P＜0.01),p-AKT fluorescence expression increased(P＜0.01),NO content decreased,T-AOC level elevated(P＜0.01);the content of MDA decreased and the activity of SOD notably rose(P＜0.01),the protein expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly increased in oxytropis falcata group(P＜0.05,P＜0.01);the level of ROS in podocytes im-proved(P＜0.01),the fluorescence expression of p-AKT decreased(P＜0.05),the content of NO upregu-lated,the content of T-AOC downregulated,and the expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 pro-tein and HO-1,GCLM,SOD mRNA decreased in in-hibitor group(P＜0.05,P＜0.01).Compared with oxy-tropis falcata group,the apoptosis rate,migration ability and intracellular ROS level of podocytes in oxytropis falcata+inhibitor group markedly in-creased(P＜0.05,P＜0.01),p-AKT fluorescence ex-pression declined(P＜0.01),MDA and NO content increased,SOD and T-AOC content decreased(P＜0.05,P＜0.01),p-PI3K/PI3K,p-AKT/AKT,Nrf2 protein and Nrf2,HO-1,GCLM,SOD mRNA expression all dramatically downregulated(P＜0.05,P＜0.01).CON-CLUSION:Oxytropis falcata extract may protect podocytes by activating the PI3K/AKT/Nrf2 signal-ing pathway,thereby improving the morphological,structural and functional changes of podocytes in-duced by high glucose and inhibiting oxidative stress response.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.

Humans ; Clinical Relevance ; Leukemia, Myeloid, Acute ; Transcription Factors ; Neoplasm Proteins ; Antigens, CD ; GPI-Linked Proteins

[Abstract] ObjectVisualizing the superficial cerebellar vein and its tributaries on suscepxibility weighted imaging (SWI), and to construct superficial cerebellar vein network. Methods According to the inclusion criteria, 80 healthy volunteers (40 males and 40 females) were selected for 3. 0 T MRI scans to obtain conventional sequence cross-section, sagittal tomographic images, and SWI image data. Post-processing was performed on the Extended MR workspace 2. 6. 3. 4 image workstation to reconstruct minimum intensity projection(mIP) images. SPSS 21. 0 statistical software was used to analyze and process each data, and the diameter measurement result were expressed as mean ± standard deviation. Results Both SWI and mIP could image the structures of the cerebellum and its veins. The cerebellar veins were divided into deep and superficial parts. The superficial cerebellar veins were divided into two groups: the vermis and the cerebellar hemispheres. The superficial vein of the cerebellar vermis consisted of superior vermis vein [diameter: (1. 21±0. 24)mm, occurrence rate: 92. 16%], summit vein [ diameter: (0. 66 ± 0. 05) mm, occurrence rate: 95%], mountain vein [diameter: (0. 76±0. 03)mm, occurrence rate: 100%], inferior vermis vein [diameter: (1. 40±0. 27)mm, occurrence rate: 99. 02%]. The superficial cerebellar hemisphere vein consists of anterior superior cerebellar vein [diameter: (1. 09± 0. 12)mm, occurrence rate: 100%], posterior superior cerebellar vein [diameter: (0. 88±0. 13) mm, occurrence rate: 70%], anterior inferior cerebellar vein [ diameter: (1. 34 ± 0. 15) mm, occurrence rate: 100%], posterior inferior cerebellar vein [ diameter: (1. 11 ± 0. 09) mm, occurrence rate: 92. 5%]. The deep veins were divided into cerebellomesencephalic fissure group, cerebellopontine fissure group, and cerebellomedullary fissure group. Conclusion SWI can display the microstructure and venules of the cerebellum, and can construct a network of superficial cerebellar veins.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Rhizoma phragmitis is a common Chinese herbal medicine whose effects are defined as 'clearing heat and fire, promoting fluid production to quench thirst, eliminating irritability, stopping vomiting, and disinhibiting urine'. During the Novel Coronavirus epidemic in 2020, the Weijing Decoction and Wuye Lugen Decoction, with Rhizoma phragmitis as the main herbal component, were included in The Pneumonia Treatment Protocol for Novel Coronavirus Infection (Trial Version 5) due to remarkable antiviral effects. Modern pharmacological studies have shown that Rhizoma phragmitis has antiviral, antioxidative, anti-inflammatory, analgesic, and hypoglycemic functions, lowers blood lipids and protects the liver and kidney. This review aims to provide a systematic summary of the botany, traditional applications, phytochemistry, pharmacology and toxicology of Rhizoma phragmitis.
Humans ; Plant Extracts/pharmacology* ; Rhizome ; Drugs, Chinese Herbal/therapeutic use* ; Antioxidants/therapeutic use* ; Antiviral Agents/therapeutic use* ; Medicine, Chinese Traditional ; Phytochemicals/therapeutic use* ; Ethnopharmacology ; COVID-19 Drug Treatment