Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

Objective To observe the clinical effect of Tongyuan Acupuncture combined with Modified Linggui Zhugan Decoction in the treatment of polycystic ovary syndrome(PCOS)with spleen deficiency and phlegm-damp syndrome.Methods A total of 86 patients with PCOS of spleen deficiency and phlegm-damp type were randomly divided into observation group and control group,43 cases in each group.The control group was treated with Metformin Hydrochloride Tablets combined with Ethinylestradiol and Cyproterone Acetate Tablets.The observation group was treated with Tongyuan Acupuncture combined with Modified Linggui Zhugan Decoction on the basis of the treatment of the control group.Both groups were treated for three consecutive months.After three months of treatment,the clinical efficacy of the two groups was evaluated.The changes of sex hormone indexes estradiol(E2),testosterone(T),luteinizing hormone(LH),follicle stimulating hormone(FSH)and prolactin(PRL)expression levels were observed before and after treatment in the two groups.The changes of glucose metabolism levels including insulin resistance index(HOMA-IR),fasting insulin(FINS)and fasting blood glucose(FPG)expression levels were compared before and after treatment between the two groups.Results(1)The total effective rate was 90.70%(39/43)in the observation group and 74.42%(32/43)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,HOMA-IR,FINS and FPG in the two groups were significantly improved(P＜0.05),and the improvement of HOMA-IR,FINS and FPG in the observation group was superior to that in the control group,the difference being significant(P＜0.05).(3)After treatment,the levels of E2,T,LH,FSH and PRL in the two groups were significantly improved(P＜0.05),and the levels of E2,T,LH,FSH and PRL in the observation group were significantly superior to those in the control group,the differences were statistically significant(P＜0.05).Conclusion Tongyuan Acupuncture combined with Modified Linggui Zhugan Decoction in the treatment of spleen deficiency and phlegm-damp type of PCOS can effectively improve the sex hormone level of patients and regulate the glucose metabolism of patients.The clinical effect is significant.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Objective:To compare the prognostic value of two predictive models based on C-reactive protein(CRP)and albumin(ALB),namely the CRP to ALB ratio(CAR)and the Glasgow prognostic score(GPS),in newly diagnosed patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed.A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical,laboratory data and follow-up information were included.The receiver operating characteristic(ROC)curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival.Furthermore,the association between CAR and baseline clinical,laboratory characteristics of patients was evaluated,and progression-free survival(PFS)and overall survival(OS)were compared between different CAR and GPS subgroups.Finally,the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.Results:ROC curve showed that the area under the curve(AUC)of CAR predicting PFS and OS in DLBCL patients was 0.687(P=0.002)and 0.695(P=0.005),respectively,with the optimal cut-off value of 0.11 for both predicting PFS and OS.Compared with the lower CAR(＜0.11)group,the higher CAR(≥0.11)group had more clinical risk factors,including age＞60 years(P=0.025),ECOG score ≥2(P=0.004),Lugano stage Ⅲ-Ⅳ(P＜0.001),non-germinal center B-cell-like(non-GCB)subtype(P=0.035),elevated lactate dehydrogenase(LDH)(P＜0.001),extranodal involved site＞1(P=0.004)and IPI score＞2(P＜0.001).The interim response evaluation of patients showed that the overall response rate(ORR)and complete response rate(CRR)in the lower CAR group were both significantly better than those in the higher CAR group(ORR:96.9％vs 80.0％,P=0.035;CRR:63.6％vs 32.5％,P=0.008).With a median follow-up of 24 months,patients with lower CAR had significantly longer median PFS and OS than those with higher CAR(median PFS:not reached vs 67 months,P=0.0026;median OS:not reached vs 67 months,P=0.002),while there was no statistical difference in PFS(P=0.11)and OS(P=0.11)in patients with GPS of 0,1,and 2.Multivariate Cox regression analysis indicated that only sex(male)and IPI score＞2 were independent risk factors for both PFS and OS.Conclusion:CAR is significantly correlated with disease progression and survival in DLBCL patients;And compared with GPS,CAR has more advantages in predicting disease outcomes in DLBCL patients.

Objective:To compare the efficacy and safety of flumatinib (FM)and imatinib (IM)as first-line treatment in newly-diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP ) in real world. Methods:A total of 84 newly-diagnosed CP-CML patients in our center from December 2019 to December 2022 were retrospectively analyzed.Among them,32 cases received FM as first-line treatment,and 52 cases received IM. Molecular response (MR),disease progression,survival and incidence of adverse events (AEs)were compared between the two groups.Results:At 3 months of treatment,the incidences of early molecular response (EMR ),MR2.0 and MR3.0 were 96.7％,70.0％ and 20.0％ in FM group,respectively,which were significantly higher than 77.1％,29. 2％ and 0 in IM group (all P<0.05 ).At 6,9 and 12 months of treatment,the incidences of major molecular response (MMR)in FM group were 68.2％,85.7％ and 90.0％,respectively,which were significantly higher than 22.9％,34.0％ and 51.1％ in IM group (all P<0.01).The median time to achieve MMR in FM group was 6(6-9)months,which was significantly shorter than 18(12-22)months in IM group (P<0.001 ).The 3-year progression-free survival rate and 3-year event-free survival rate in FM group were 100％ and 68.8％,respectively,while in IM group were 98.1％ and 55.8％.There were no significant differences between the two groups (P>0.05). The incidence of grade 3-4 hematologic AEs in FM group was 21 .9％,which was slightly lower than 25.0％ in IM group,but the difference was not significant (P>0.05 ).Conclusion:In real clinical practice,FM as first-line treatment achieves MMR earlier than IM,and exhibits good safety profile in newly-diagnosed CML-CP patients,which potentially leads to improved long-term survival and treatment-free remission.

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.

OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR _PFS=2.047, P =0.039; HR _OS=4.854, P =0.001). CONCLUSION Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.
Humans ; Prognosis ; Fibrinogen ; Disease-Free Survival ; Albumins/therapeutic use* ; Hemostatics/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

This study was aimed at identifying the bioactive components of the crude and stir-baked hawthorn for invigorating spleen and promoting digestion, respectively, to clarify the processing mechanism of hawthorn by applying the partial least squares(PLS) algorithm to build the spectrum-effect relationship model. Firstly, different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions were prepared, respectively. Then, the contents of 24 chemical components were determined by ultra-high performance liquid chromatography-mass spectrometry. The effects of different polar fractions of crude hawthorn and stir-baked hawthorn aqueous extracts and combinations of different fractions were evaluated by measuring the gastric emptying rate and small intestinal propulsion rate. Finally, the PLS algorithm was used to establish the spectrum-effect relationship model. The results showed that there were significant differences in the contents of 24 chemical components for different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions, and the gastric emptying rate and small intestinal propulsion rate of model rats were improved by administration of different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions. The bioactive components of crude hawthorn identified by PLS models were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, neochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, malic acid, quinic acid and fumaric acid, while neochlorogenic acid, cryptochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, quinic acid and fumaric acid were the bioactive components of stir-baked hawthorn. This study provided data support and scientific basis for identifying the bioactive components of crude and stir-baked hawthorn, and clarifying the processing mechanism of hawthorn.
Animals ; Rats ; Spleen ; Crataegus ; Quinic Acid ; Least-Squares Analysis ; Vanillic Acid ; Algorithms ; Digestion