This study used the natural flavonoid compound silybin as the parent compound and synthesized 16 silybin derivatives through oxidative dehydrogenation, alkylation, selective demethylation, and acylation. The structures of these derivatives were confirmed by 1H NMR, 13C NMR, and MS. All derivatives were found to be new compounds never reported in previous literature. Using gastric cancer cell line SGC-7901 and human glioblastoma cell line LN-229, the in vitro anti-tumor activity of the novel silybin derivative was determined through MTT assay with lapatinib as the positive control. The experimental results indicate that the synthesized novel silybin derivatives have a certain degree of anti-proliferative effect on two types of cancer cells, with compounds I2 and I14 showing strong anti-proliferative activity against LN-229 and SGC-7901 cells.

Objective To observe the analgesic effects of mild moxibustion on primary dysmenorrhea(PD)rats with cold and dampness stagnation syndrome and its effect on BDNF/TrkB signaling pathway in hypothalamus;To explore its mechanism for the treatment of PD.Methods A total of 32 Wistar non-pregnant female rats were randomly divided into blank group,model group,Western medicine group and mild moxibustion group,with 8 rats in each group.Except for the blank group,the other groups received estradiol benzoate intraperitoneal injection combined with ice bath treatment + oxytocin intraperitoneal injection to establish PD with cold and dampness stagnation syndrome model.The mild moxibustion group received treatment at"Shenque"and"Guanyuan"from the eighth day of modeling for 10 min,and the Western medicine group was given ibuprofen solution intragastically for 4 days.The latency period of rats twisting was observed and the twisting score was calculated,Western blot and PCR were used to detect the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue.Results Compared with the blank group,the model group showed a shortened latency period and an increased twisting score(P<0.01),the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Compared with the model group,the mild moxibustion group had a longer latency period and lower twisting score(P<0.01),while the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Conclusion Mild moxibustion may effectively improve the pain state of PD rats with cold and dampness stagnation syndrome.This mechanism may be related to downregulating c-fos expression,inhibiting BDNF/TrkB signaling pathway activation,thereby inhibiting pain signal transmission,regulating pain occurrence and maintenance.

With the rapid development of information technology,what has been widely used in the field of medical and health care includes the home detection of aging population in communities,intelligent health management,special patient positioning care management,information sharing,and interconnection management,which has also brought new opportunities for the innovative management of medical equipment in recent years.We have taken"sense,knowledge and action"as the core,and effectively improved the level of lean management of medical equipment through data acquisition,data modeling and analysis,and remote service or decision response.This paper aims to summarize the application and research progress of intelligent information technology in the lean management of medical equipment in order to provide new ideas for the refined management of medical equipment.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To observe the effects of preventative moxibustion on analgesia,substance P(SP),prostaglandin(PG)F2α and PGE2 in rats with dysmenorrhea due to cold-dampness stagnation,and to explore the analgesic mechanism. Methods:Sixty-four female Wistar non-pregnant rats were randomly divided into a blank group,a model group,a Western medicine group,and a preventative moxibustion group,with 16 rats in each group.Eight qualified diestrus rats were selected from each group.Except for the blank group,the other three groups established models of dysmenorrhea due to cold-dampness stagnation using an ice water bath combined with estradiol benzoate and oxytocin.On the 8th day after modeling,the preventative moxibustion group was treated with gentle moxibustion at Shenque(CV8)and Guanyuan(CV4),and the Western medicine group was given ibuprofen solution for 4 consecutive days.On the 11th day,the intervention groups(i.e.the Western medicine group and the preventative moxibustion group)were treated once again after being injected with oxytocin.The writhing score and the pain threshold of rats were determined;the serum levels of brain-derived neurotrophic factor(BDNF),SP,PGF2α,and PGE2 were measured;the mRNA and protein expression levels of BDNF and its receptor tropomyosin receptor kinase B(TrkB)in the spinal dorsal horn and hypothalamus were detected. Results:Compared with the blank group,the writhing score increased(P<0.01),the pain threshold decreased(P<0.01),the serum levels of BDNF,SP,and PGF2α increased(P<0.01),while the PGE2 decreased(P<0.01);the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus increased(P<0.01)in the model group.Compared with the model group,the writhing score decreased,the pain threshold increased,the serum BDNF,SP,and PGF2α levels decreased significantly,the serum PGE2 level increased,and the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus decreased significantly in the preventative moxibustion group and the Western medicine group,while the inter-group differences were significant(P<0.01).Compared with the Western medicine group,the writhing score decreased,the pain threshold increased,the serum BDNF,SP,and PGF2α,levels decreased,the serum PGE2 level increased,and the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus in the preventative moxibustion group decreased significantly,while the inter-group differences were significant(P<0.05 or P<0.01). Conclusion:Preventative moxibustion at Shenque(CV8)and Guanyuan(CV4)can improve the pain sensitization state of rats with dysmenorrhea due to cold-dampness stagnation,down-regulate the mRNA and protein expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus;regulation of the serum SP,PGF2α,and PGE2 levels may be part of the mechanism.

Objective:To observe the effects of sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the writhing reaction and score,the temperature and blood flow perfusion of moxibustion point area and uterus,the serum levels of arginine vasopressin(AVP),prostaglandin(PG)F2α,and thromboxane(TX)B2 in rats with primary dysmenorrhea(PD)due to cold-dampness stagnation,and to explore the possible mechanism of sparrow-pecking moxibustion in treating PD.Methods:Thirty-two healthy non-pregnant female Wistar rats were randomly divided into a normal group,a model group,an ibuprofen group,and a sparrow-pecking moxibustion group,with 8 rats in each group.Except for the normal group,the other three groups were subjected to modeling with cold water bath combined with estradiol benzoate and oxytocin injection.Rats in the sparrow-pecking moxibustion group were treated with sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the 8th day of modeling,30 min/time,once a day for 3 d;those in the ibuprofen group were treated with 0.8 mL ibuprofen solution(a specification of 125 mg in 10 mL)on the 8th day of modeling,once a day for 3 d;those in the normal group and the model group were given 0.8 mL normal saline,once a day for 3 d.On the 11th day,rats in each group were intraperitoneally injected with oxytocin(2 U/rat),and the writhing incubation period and writhing score in 20 min were observed;the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus in vivo were detected;the serum levels of AVP,PGF2α,and TXB2 were determined.Results:The writhing incubation period was significantly longer(P<0.01)and the writhing score was significantly lower(P<0.01)in the sparrow-pecking moxibustion group and the ibuprofen group than in the model group;compared with the ibuprofen group,the writhing incubation period was prolonged(P<0.01)and the writhing score was decreased(P<0.01)in the sparrow-pecking moxibustion group;compared with the normal group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly decreased,while the serum PGF2α,AVP,and TXB2 levels were significantly increased(P<0.01)in the model group;compared with the model group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased,and the serum levels of PGF2α,AVP,and TXB2 were significantly decreased in the ibuprofen group and the sparrow-pecking moxibustion group(P<0.05 or P<0.01);compared with the ibuprofen group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased(P<0.05),the serum AVP and TXB2 levels were significantly decreased(P<0.05),while the serum PGF2α level had no statistical difference in the sparrow-pecking moxibustion group(P>0.05).Conclusion:Sparrow-pecking moxibustion had a remarkable analgesic effect on the rats with PD due to cold-dampness stagnation,and the mechanism may be related to the increased temperature and blood perfusion of the moxibustion point area and uterus,as well as the decreased serum PGF2α,AVP,and TXB2 levels.

Objective:To investigate the therapeutic effect and safety of pomadomide combined with cyclophosphamide and dexamethasone (PCD) in the treatment of relapsed/refractory multiple myeloma (MM).Methods:The clinical data of 20 relapsed/refractory MM patients receiving PCD regimen in the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College from March 2021 to June 2022 were retrospectively analyzed; and 29 relapsed/refractory MM patients receiving other regimens including DECP (dexamethasone+etoposide+cyclophosphamide+cisplatin, 13 cases) and VCD (bortezomib+ cyclophosphamide+ dexamethasone, 16 cases) during the same period were treated as the control group. The efficacy and adverse effects of both groups were compared after 4 cycles of treatment.Results:After 4 cycles of treatment, the overall response rate (ORR) and the clinical benefit rate (CBR) of 20 cases in PCD group was 70.0% (14/20) and 85.0% (17/20), respectively; among 20 cases, there were 5 cases of complete response (CR), 4 cases of very good partial remission (VGPR), 5 cases of partial remission (PR), 3 cases of minimal remission (MR), 2 cases of stable disease (SD), 1 case of the progression of the disease (PD). ORR and CBR of 29 cases in the control group was 41.4% (12/29) and 65.5% (19/29), respectively; among 29 cases, there were 2 cases of CR, 3 cases of VGPR, 7 cases of PR, 7 cases of MR, 5 cases of SD, 5 cases of PD. There was a statistically significant difference in ORR of both group ( χ2 = 3.89, P = 0.048), while the difference in CBR of both group was not statistically significant ( χ2 = 2.30, P = 0.129). There were 2 patients with renal impairment achieving CR in PCD group and 1 patient with renal impairment achieving CR in the control group ( P = 0.152); 1 genetically high-risk patient achieved CR in PCD group and none of patients in the control group achieved CR, and the difference was statistically significant ( P>0.05). The common hematological adverse effects of two groups were anemia, neutropenia, thrombocytopenia; the common non-hematological adverse effects were malaise, infection and fatigue, and the differences were statistically significant (all P>0.05). The incidence of grade 3-4 infection was 25.0% (5/20) in PCD group and the disease was under the control after anti-infective therapy, and the incidence of grade 3-4 infection was 24.1% (7/29) in the control group; and the difference was not statistically significant ( P > 0.05). Conclusions:PCD regimen has good clinical efficacy and safety in treatment of relapsed/refractory MM.

Silibinin is a kind of flavonoid extracted from the dried ripe fruit of Silybum marianum，a plant of compositae. It has a variety of pharmacological activities and can effectively prevent and treat diabetes and its complications. This paper reviews the research progress on the mechanism of silibinin in the prevention and treatment of diabetes and its complications. It is found that silibinin can prevent and treat diabetes by up-regulating the expression of estrogen receptor-α，activating the duodenum-brain-liver axis pathway and stabilizing the protein structure. It can prevent and cure the nervous system diseases of diabetes by activating glucagon-like peptide-1 receptor/protein kinase A signal pathway and inhibiting the hyperphosphorylation of tau protein. It can prevent and treat diabetic retinopathy by down-regulating the expression and activity of pro-inflammatory，pro-oxidative factors and histone deacetylase 6. It can prevent diabetic nephropathy by activating protein kinase B signal pathway and reducing the level of transforming growth factor-β1，and prevent and treat diabete’s obesity by inhibition of hepatobiliary transporter CD36 expression， and suppressing nuclear factor-κB pathway and its downstream expression of pro-inflammatory cytokines（tumor necrosis factor-α and interleukin-1β），etc.

Ebola virus (EBOV) is an extremely contagious pathogen first discovered in Africa associated with severe hemorrhagic disease in humans and nonhuman primates, which has resulted in at least 28 500 suspected cases and 11 300 confirmed deaths in 2014-2016 Ebola epidemic in West Africa. Rapid and sensitive detection of EBOV is the key to increasing the probability of survival and reducing infection rates in pandemic regions. Here, we report an ultrasensitive and instrument-free EBOV detection assay based on colloidal carbon immunochromatography. Carbon nanoparticle-labeled rabbit anti-EBOV-VP40 IgG were concentrated in the conjugate pad, monoclonal antibody (McAb, 4B7F9) against EBOV-VP40 and goat anti-rabbit IgG were immobilized on the nitrocellulose membrane with 2 μL/cm at a concentration of 1 mg/mL as test and control lines, respectively. Then the sample application pad, conjugate release pad, nitrocellulose membrane and absorbent pad were assembled into a lateral flow test strip. The test strip shows strong specificity against related viruses that share similar clinical symptoms and geographic range with EBOV, including marburg virus, influenza virus, yellow fever virus and dengue virus. In addition, 1 500 negative serums were tested with false-positive rate of 1.3‰ which significantly lower than that of ReEBOV™ colloidal gold test kit recommended by World Health Organization (WHO). The sensitivity of this strip was analyzed using inactivated EBOV with detection limit of 100 ng/mL (10⁶ copies/mL) which clearly higher than that of ReEBOV™ dipstick (10⁸ copies/mL). Furthermore, the strip showed excellent thermal stability characteristics in room temperature and could be as a point-of-care (POC), ultra-sensitive and specific promising candidate for EBOV serological screening in rural Africa or entry/exit ports.
Animals ; Carbon ; Ebolavirus ; Hemorrhagic Fever, Ebola ; Humans ; Nanoparticles ; Rabbits

Objective:To explore the effect of 14-3-3εprotein on the localization of Cdc25B protein during the meiotic resumption of mouse oocytes,and to pay foundation for the further study on the molecular mechanism of 14-3-3εprotein in regulating the development of mouse oocytes.Methods:The Kunming genealology female mice aged 3 weeks were used to obtain the germinal vesicle (GV)-stage oocytes after superovulation.The GV-stage oocytes were divided into non-injection group,control siRNA injection group and 14-3-3εsiRNA injection group. The pmax-FP-Red-HA-14-3-3εexpression vector was constructed.Indirect immunofluorescence was used to observe the colocalization of 14-3-3εprotein and Cdc25B protein in the mouse oocytes;direct immunofluorescence was used to observe the subcellular localization of 14-3-3εprotein and Cdc25B protein in the mouse oocytes;14-3-3εsiRNA was microinj ected into the GV-stage oocytes;the morphology was observed under phase-contrast microscope;the germinal vesicle breakdown (GVDB)rates of the mouse oocytes were calculated;the expression level of 14-3-3εprotein and the relative expression level of Cdc2-pTyr15 protein were observed by Western blotting method;the matuation-promoting factor (MPF)activity in the oocytes was measured by autoradiography.Results:The indirect immunofluorescence and direct immunofluorescence results showed that the 14-3-3εprotein and wild Cdc25B protein were co-localized in the cytoplasm;Cdc25B was translocated from the cytoplasm to the nucleus shortly before GVBD.When the Ser321 of Cdc25B protein turned into Ala,the expression level of 14-3-3εprotein was decreased. None of the oocytes in non-injection group and control siRNA injection group were able to undergo GVBD until at least 24 h after injection,there was no significant differences in the rate of GVBD between non-injection group and control siRNA injection group (P>0.05);the GVBD rates of oocytes in 14-3-3εsiRNA injection group at 22 and 24 h after injection were significantly higher than those in non-injection group and control siRNA injection group (P<0.01);the rate of oocytes progressed to metaphaseⅡ (MII)in 14-3-3εsiRNA injection group at 24 h after injection was significantly higher than those in non-injection group and control siRNA injection group (P<0.01). Conclusion:Ser321 might be involved in the process of regulating the subcellular localization of Cdc25B by 14-3-3εprotein in the meiotic resumption of mouse oocytes.