AIM To investigate the effects of diosgenin on autophagy of human osteosarcoma cells.METHODS Human osteosarcoma MG63 and U2OS cells with or without exposure to diosgenin had their proliferation detected by MTT assay,their ultrastructure observed by transmission electron microscopy,their expression of autophagy protein Beclin1 observed by immunofluorescence staining,and their expressions of autophagy molecular markers LC3,Beclin1 and PI3K/Akt/mTOR signaling pathway related proteins detected by Western blot.The MG63 and U2OS cells cotreated with diosgenin and PI3K pathway inhibitor LY294002 had the expression of Beclin1 mRNA detected by RT-qPCR.The MG63 and U2OS cells cotreated with autophagy inhibitor 3-methyladenine(3-MA)had their inhibition rate of proliferation detected by MTT assay,their expression of cleaved-caspase3 protein detected by Western blot,and their expression of caspase3 mRNA detected by RT-qPCR.RESULTS Upon osteosarcoma MG63 and U2OS cells,diosgenin inhibited their proliferation,promoted the generation of autophagosomes,increased the protein expression of LC3 Ⅱ and Beclin1(P<0.05,P<0.01),reduced the protein expression of LC3 I(P<0.01),and inhibited the protein phosphorylation level of PI3K/Akt/mTOR pathway(P<0.05,P<0.01),whose effects were offset by the intervention with autophagy inhibitors in terms of the reduced proliferation inhibition and down-regulated expressions of caspase3 mRNA and cleaved-caspase3 protein(P<0.01).CONCLUSION Diosgenin can inhibit the proliferation of osteosarcoma cells and induce their autophagy leading to their death and autophagy apoptosis,which may be related to the activation of PI3K/Akt/mTOR signaling pathway and up-regulation of the expression of LC3 Ⅱ and Beclin1 proteins.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Tumor is a kind of disease with high morbidity, high mortality and poor prognosis. Chemotherapy is the main treatment of tumor, but the problem of chemotherapy resistance is becoming increasingly prominent, so finding ways to overcome chemotherapy resistance and improve the therapeutic effect has become an urgent problem to be solved. At present, with the development of research, the anti-tumor effect of some traditional Chinese medicine has attracted extensive attention. Berberine, traditionally used in the treatment of digestive system diseases, has been proved to have the effect of anti-tumor and reversing tumor multi-drug resistance. This review summarizes the recent researches on the reversion multi-drug resistance in tumor by berberine, in order to explore the means to improve the therapeutic effect and prognosis of tumor drug resistance.

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 μm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Quality Control

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
Cross-Sectional Studies ; Diabetes Mellitus/epidemiology* ; Humans ; Hyperlipidemias/epidemiology* ; Hypertension/epidemiology* ; Macular Degeneration/etiology* ; Risk Factors

This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml^-2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml^-2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml^-2 could be potential criteria for the Chinese population to omit prompt biopsy safely.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Prostate-Specific Antigen ; Multiparametric Magnetic Resonance Imaging ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Biopsy ; Image-Guided Biopsy/methods*

The efficacy and safety of Xiao'er Chaigui Tuire Granules for the treatment of hand, foot and mouth disease were syste-matically evaluated. Four Chinese databases of CNKI, CBM, WanFang, VIP and four English databases of PubMed, Cochrane Library, EMbase, Web of Science were retrieved by computers. With Chinese and English words "Xiao'er Chaigui Tuire Granules" "hand, foot and mouth disease" as the subject and keywords, randomized controlled trials(RCT) for the effect of Xiao'er Chaigui Tui-re Granules alone and combined with Western medicine in the treatment of hand, foot and mouth disease were retrieved, and the retrieval time was generally from the establishment of the database to January 20, 2020. Then all the relevant documents that meet the requirements and be included in the quality evaluation standard were screened out, relevant baseline data information was extracted, and a final evaluation was conducted for the quality of relevant literatures. The quality evaluation was conducted by the latest RevMan 5.3 software version-based tools. The reliability of the data relating to the results of the literatures was analyzed by statistical data. A total of 7 RCTs were included. The total sample size was 619, including 321 in the experimental group and 298 in the control group. Meta-analysis results show that: Xiao'er Chaigui Tuire Granules could improve the total clinical effectiveness(RR=1.28, 95%CI[1.11, 1.46], P=0.000 4; RR=1.62, 95%CI[1.06, 2.48], P=0.02); Xiao'er Chaigui Tuire Granules combined with Western medicine could significantly shorten the healing time of oral ulcers in children with hand, foot and mouth disease(MD=-1.11, 95%CI[-1.44,-0.78], P<0.000 01; MD=-2.13, 95%CI[-2.37,-1.89], P<0.000 01; MD=-1.10, 95%CI[-1.38,-0.82], P<0.000 01); on the basis of conventional treatment, Xiao'er Chaigui Tuire Granules combined with Western medicine could reduce the fever time(MD=-1.21, 95%CI[-2.15,-0.27], P=0.01; MD=-1.93, 95%CI[-2.35,-1.51], P<0.000 01; MD=-2.00, 95%CI[-2.60,-1.40], P<0.000 01), with no serious adverse reaction. The results showed that, in the treatment of hand, foot and mouth disease, compared with the conventional treatment method of Western medicine alone, the combined use of Xiao'er Chaigui Tuire Granules had more obvious advantage in effectively shortening the healing time of oral ulcers in children and effectively reducing the antipyretic time. Moreover, it had a better clinical efficacy in treating the patients with hand, foot and mouth disease in the early stage in terms of the improvement and control of symptoms and pathology, with a significantly increased effectiveness and no serious adverse reaction. It could be considered to be combined with therapies based on syndrome differentiation. However, due to the small sample size of clinical studies currently included, and the low quality of clinical studies further included, the quality of the studies included was low, which affected the scientific reliability and quality of the conclusions of the study. Therefore, further clinical results are still required for further confirmation.
Child ; Drugs, Chinese Herbal ; Hand, Foot and Mouth Disease ; Humans ; Reproducibility of Results ; Treatment Outcome

【Objective】 To investigate the expression and significance of phosphorylated receptor tyrosine kinase(p-AXL) in diffuse large B cell lymphoma(DLBCL), and the clinical value of its co-expression with BCL-2 and /or c-MYC split gene. 【Methods】 Totally 118 cases of DLBCL were collected in the First Affiliated Hospital of Sun Yat-sen University from 2012 to 2017, and prepared as tissue array. p-AXL, c-MYC and BCL-2 proteins were detected by immunohistochemistry, and c-MYC split gene was detected by FISH staining. 【Results】 p-AXL protein was stained on tumor cells’membrane or in the cytoplasm of DLBCL cells. p-AXL was expressed more commonly in Non-GCB type than in GCB type. The expression of p-AXL was significantly correlated with the chemotherapy effect(P<0.01), and the expression of c-MYC split gene or BCL-2 protein separately(P<0.01). Co-expression of p-AXL and c-MYC, or BCL-2, or both of them was significantly correlated with the Hans typing(P<0.01). The PFS of p-AXL positive patients was obviously lower than that of p-AXL negative patients(P<0.05). The OS of p-AXL positive patients was also lower than that of the negative patients, but the difference had no statistical significance(P>0.05). Univariate analysis showed that p-AXL and male, p-AXL and Non-GCB type, p-AXL and c-MYC co-expression, p-AXL and c-MYC and/or BCL-2 co-expression were the risk factors for PFS and OS in DLBCL patients(P<0.05). Multivariate analysis showed that p-AXL positive in male(P<0.05) and p-AXL/c-MYC co-expression(P<0.01) were independent risk factors for PFS and OS in DLBCL patients. 【Conclusions】 p-AXL protein is expressed in DLBCL, and its expression is significantly related to the expression of c-MYC and BCL-2. p-AXL expression is associated with lower chemotherapy response rate, shorter progression-free survival and shorter overall survival. p-AXL/c-MYC co-expression or p-AXL positive in male may be an independent prognostic factor for DLBCL patients.

Objective:To study the pathological changes of the spleen in patients with COVID-19 and to analyze the relationship between the weakened immune system and splenic lesions.Methods:Postmortem needle autopsies from the spleen were carried out on 10 patients who died from COVID-19 in Wuhan. Routine hematoxylin and eosin (HE) staining was used to observe the pathological changes. The changes of lymphocytes were studied further with immunohistochemistry.RT-PCR was used to detect 2019-nCoV RNA in the spleen. In addition,the Epstein-Barr virus (EBV) was detected by in situ hybridization, and coronavirus particles were detected by transmission electron microscopy in 2 cases.Results:There were 7 males and 3 females, with an average age of 68.3 years.Of the 10 cases, 4 had cancer history and another 4 had other underlying diseases respectively.Cough, fever, malaise and dyspnea were the main clinical symptoms.The time from onset to death was 15-45 days.Ten cases patients had normal or slight increase in peripheral blood leukocyte count in the early stage of the disease, 6 cases had significant increase before death. Five patients′ peripheral blood lymphocyte count decreased in the early stage of the disease, and 10 patients′ peripheral blood lymphocyte count decreased significantly before the disease progressed or died. Seven cases were treated with corticosteroid (methylprednisolone ≤40?mg/d, not more than 5 days). Histopathological examination showed that the cell composition of the spleen decreased, white pulp atrophied at different levels, meanwhile lymphoid follicles decreased or absent;in addition, the ratio of red pulp to white pulp increased with varying degrees. In 7 cases, more neutrophil infiltration was found, and in 5 cases, scattered plasma cell infiltration was found. Macrophage proliferation and hemophagocytic phenomena in a few cells were found in a case. Meanwhile, necrosis and lymphocyte apoptosis were detected in 2 cases, small artery thrombosis and spleen infarction in 1 case, and fungal infection in 1 case. The results of immunohistochemistry showed that the T and B lymphocyte components of the spleen in all cases decreased in varying degrees. CD20 + B cells were found to accumulate in the lymphoid sheath around the splenic artery in 8 cases. However, CD20 and CD21 immunostaining in 2 cases showed that the number of white pulp was almost normal, and splenic nodules were atrophic. CD3 +, CD4 + and CD8 +T cells were decreased. In 9 cases,CD68 + macrophages were no significant changes in the distribution and quantity. While more CD68 + cells were found in the medullary sinuses of 1 case (related to fungal infection). Few CD56 + cells were found. EBV was negative by in situ hybridization. RT-PCR was used to detect the nucleic acid of 2019-nCoV. One of 10 cases was positive, 39 years old,who was the youngest patient in this group, and the other 9 cases were negative. Coronavirus particles were found in the cytoplasm of macrophage under electron microscope in 2 cases. Conclusions:The death of COVID-19 occurs mainly in the elderly, and some cases have no underlying diseases. Spleen may be one of the organs directly attacked by the virus in some patients who died from COVID-19. T and B lymphocyte in the spleen decrease in varying degrees, lymphoid follicles are atrophied, decreased or absent, and the number of NK cells do not change significantly. And the pathological changes of the spleen are not related to the use of low dose corticosteroid, which may be related to the direct attack of virus and the attack of immune system on its own tissues.