Metabolomic mechanism and pharmacodynamic material basis of Buxue Yimu pills in the treatment of anaemia in women of reproductive age.

Objective: To explore the pharmacological basis and mechanism of Buxue Yimu pills (BYP) in the treatment of anaemia in women from the perspective of metabolomics and network analysis. Materials and Methods: Forty-six women of reproductive age with haemoglobin 70-110 g/L were recruited. Blood samples were collected before and after 4 weeks of oral BYP treatment to assess the changes in haemoglobin, coagulation function, and iron metabolism indices. An integrated analysis of metabolomics (liquid chromatography mass spectrometry) and network analysis was performed to identify the potential pharmacodynamic mechanisms of BYP. Results: After BYP treatment, the haemoglobin level of patients significantly increased from 93.67 ± 9.77 g/L to 109.28 ± 12.62 g/L (p < 0.01), while no significant changes were found in iron metabolism and coagulation-related indicators. A total of 22 differential metabolites were identified after metabolomics analysis, which were mainly related to the inhibition of inflammation and oxidative stress. Integrating pharmacodynamics and metabolomics, a network of drug-active components-targets-metabolic pathways-metabolomics was established. Acetylcholinesterase, phospholipase A2 group IIA, and phospholipase A2 group IVA may be the most promising therapeutic targets. Conclusion: BYP can inhibit inflammation and oxidative stress as well as promote haematopoiesis, potentially improving anaemia.

Changes of choroidal structure in children with hyperopic amblyopia observed by EDI-OCT technique / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the differences in choroidal structure between hyperopic amblyopia and normal children of the same age by the enhanced depth imaging optical coherence tomography(EDI-OCT)technique.METHODS: There were 35 cases in 50 eyes of children with hyperopic amblyopia visiting our hospital in January 2021 to December 2021 selected in the amblyopic group, and 30 cases in 51 eyes of healthy children who matched general data in the same period were selected in the control group. EDI-OCT examination was performed to measure the choroidal thickness(CT). After image processing, the total choroidal area(TCA), luminal area(LA), stromal area(SA)and choroidal vascularity index(CVI)were obtained.RESULTS: TCA(except inferior quadrant), SA(except inferior quadrant of the outer ring), LA and CT(except inferior and temporal quadrant )in the amblyopic group of each area were significantly larger than that in the control group(P&#x003C;0.05), and there was no significant difference in CVI between the two groups except the temporal quadrant of the outer ring(P&#x003E;0.05). There was no significant difference in CT for all degrees of hyperopic amblyopia, with the exception of the nasal quadrant(P&#x003E;0.05).CONCLUSION: Hyperopic amblyopia is accompanied with abnormal choroidal structure. As the degree of hyperopia increases, TCA, LA and SA exhibit increasing trends. The changes in choroidal structure are presumed to be related to hyperopic amblyopia.

Clinical study of warm needling moxibustion plus intra-articular injection of sodium hyaluronate for chondromalacia patellae / 针灸推拿医学（英文版）

Objective: To observe the therapeutic efficacy of warm needling moxibustion plus intra-articular injection of sodium hyaluronate in treating chondromalacia patellae and its effect on inflammatory factors in knee joint fluid. Methods: Sixty-eight patients with chondromalacia patellae were randomized into a control group and an observation group, with 34 cases in each group. The control group was treated with intra-articular injection of sodium hyaluronate, while the observation group was given additional warm needling moxibustion treatment. Before and after treatment, the two groups were scored using Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and visual analog scale (VAS), examined by magnetic resonance imaging (MRI) and determined for the levels of nuclear factor-κB (NF-κB), tumor necrosis factor (TNF)-α and interleukin (IL)-1β in knee joint fluid. Clinical efficacy was estimated after treatment. Results: The effective rate was higher in the observation group than in the control group (P<0.05). After treatment, the scores of pain, stiffness and daily activities, as well as the general score of WOMAC declined significantly in both groups (all P<0.05), and were lower in the observation group than in the control group (all P<0.05); the time cost for climbing up and down one staircase and VAS score decreased markedly in both groups (all P<0.05), and were shorter or lower in the observation group than in the control group (both P<0.05); the MRI grading showed no significant change in the control group after intervention (P>0.05), while the grading in the observation group showed notable improvement (P<0.05), and was better than that in the control group (P<0.05); the levels of NF-κB and IL-1β in knee joint fluid dropped significantly in the control group after treatment (both P<0.05), while the levels of NF-κB, TNF-α and IL-1β in knee joint fluid all decreased significantly in the observation group (all P<0.05) and were lower than those in the control group (all P<0.05). Conclusion: Warm needling moxibustion plus intra-articular injection of sodium hyaluronate can produce definite efficacy in treating chondromalacia patellae; it can mitigate the clinical symptoms, improve the lesion extent of chondromalacia and down-regulate the levels of NF-κB, TNF-α and IL-1β in knee joint fluid.

[Effect of Panax japonicus saponin â £a on alleviating nonalcoholic steatohepatitis by regulating miR-17-5p/MFN2 signaling pathway].

To study the effect of Panax japonicas saponin Ⅳa(SPJ-Ⅳa) on nonalcoholic steatohepatitis(NASH) through miR-17-5 p/MFN2 signaling pathway. The nonalcoholic steatohepatitis model was induced by a high-fat diet combined with CCl_4 in Balb/c male mice. The mouse serum and liver were collected, the body weight and liver weight were measured, the liver index was calculated, and the serum biochemical indicators alanine amino transferase(ALT), triglyceride(TG), and glucose(Glu) were measured. The morphological changes in the liver were detected by HE and Masson staining, Real-time PCR was used to detect lipid metabolism-related genes, inflammation-related genes interleukin-6(IL-6) and interleukin-1ß(IL-1ß), miR-17-5 p and MFN2 expressions, and Western blot was used to detect MFN2 protein expression level. Compared with the normal control group, the liver index in the HFD+CCl_4 group was significantly increased, and the contents of ALT, TG, and Glu were significantly increased; the morphology showed obvious steatosis and collagen fiber deposition; mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p increased significantly, the mRNA expression level of MFN2 decreased significantly, and the protein level of MFN2 decreased. After intervention with SPJ-Ⅳa, the levels of ALT, TG and Glu decreased, morphological steatosis decreased, collagen fiber deposition decreased, and mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p decreased. The mRNA expression level of MFN2 increased, and the protein level of MFN2 also increased. The results of this study indicated that miR-17-5 p/MFN2 signaling pathway may be involved in the occurrence and development of NASH, and SPJ-Ⅳa had a protective effect on NASH, its mechanism may be related to the regulation of miR-17-5 p/MFN2 signaling pathway.

Insulin Resistance in Polycystic Ovary Syndrome Improved by Chinese Medicine Dingkun Pill (): A Randomized Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS).@*METHODS@#A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated.@*RESULTS@#Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05).@*CONCLUSION@#DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).

Water-soluble extract of clove inhibits in vitro and in vivo growth of colon cancer by inducing autophagy / 中国药理学与毒理学杂志

OBJECTIVE Cloves(Syzygium aromaticum L.)have been used as both a spice and a traditional Chinese medicinal herb for thousands of years. However, relatively little is known about its potential anticancer activity and mechanisms.In this study,we investigated the in vitro and in vivo anti-tumor effects and mechanisms of water extract of cloves(WEC)against colorectal cancer. METHODS MTS assay and Colony-formation assay were used to detect the anti-tumor activity of WEC on HT-29 cells.The in vivo anti-tumor effect of WEC was detected in a subcutaneous transplantation tumor model of human HT-29 cells.Autophagy was detected by flow cytometry and the expressions of autophagy related proteins(Beclin-1 and LC-3a/b)were determined by western blot. RESULTS MTS result showed that WEC significantly inhibited the viability of HT-29 cells,with the IC50values of 150 μg·mL-1.The colony-formation assay showed that the WEC significantly suppressed colon cancer cells proliferation.WEC also exhibited significant antitumor activity in tumor bearing nude mice. Flow cytometry result showed that WEC significantly induced autophagy, and the averaged relative values of fluorescence intensity were 206,251,341 and 356 in cells treated with 0,100,150 and 200 μg·mL-1WEC for 48 h.Western blot result showed that WEC treatment significantly increased Beclin-1 expression and ratios of LC3-II/LC3-I. CONCLUSION These result showed that WEC inhibited the growth of colon tumor both in vitro and in vivo, which might be related with autophagy induction, and WEC has potential to be developed as a novel anticancer agent for the treatment of colon cancer.

Zn-doped CuO nanocomposites inhibit in vitro and in vivo growth of pancreatic cancer by inducing autophagy through AMPK/mTOR pathway / 中国药理学与毒理学杂志

OBJECTIVE Zn-doped CuO nanocomposites (Zn-CuO NPs) are novel nanoparticles synthesized by our research group.In this study,we assessed the in vitro and in vivo antitumor effects of Zn-CuO NPS on pancreatic cancer cells,as well as the potential mechanisms. METHODS MTS assay was used to detect the effects of Zn-CuO NPS on proliferation pancreatic cancer cells(Panc-mia and Aspc-1). The in vivo antitumor effects of Zn-CuO NPs were detected by xenografts model in nude mice. The effects of Zn-CuO NPS on autophagy were detected bytransmission electron microscopy (TEM) andflow cytometry. Autophagy related proteins were detected by Western blotting. RESULTS Zn-CuO NPS significantly inhibited the proliferation of Panc-mia cells and Aspc-1 cells.In vivo experi-ments showed that Zn-CuO NPS significantly inhibited the tumor growth in nude mice without affecting the body weight of the mice. TEM and flow cytometry showed that Zn-CuO NPS induced autophagy, and significantly increased the number of autophagosome.Western Blot showed that Zn-CuO NPS alterd the expression of autophagy related proteins,such as AMPK,mTORand Beclin-1.Also,AMPK inhibitor could significantly reduce Zn-CuO NPS-induced autophagy pathwayas analyzed byWestern blotting. CONCLUSION The findings suggested that Zn-doped CuO nanocomposites inhibited the in vitro and in vivo growth of pancreatic cancer by inducing autophagy through AMPK/mTOR pathway.

Granulin A synergizes with cisplatin to inhibit the growth of human hepatocellular carcinoma / 中国药理学与毒理学杂志

OBJECTIVE Granulin A (GRN A), a cytokinesis protein, is derived from proteolysis of progranulin. The previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly. This study aimed to investigate the effect of combination of GRN A and cisplatin on in vitro and in vivo on the growth of hepatocellular carcinoma. METHODS The in vitro and in vivo antitumor effects of combination of GRN A and Cisplatin were evaluated with MTS assay and subcuta-neous transplantation tumor model.Chou-Talalay method was used to calculate the combination index (CI). Colony formation assay and flow cytometry were used to detect the effects of GRN A on apoptosis. The expression of apoptosis-related proteins were detected by Western blot. RESULTS MTS assay showed that GRN A significantly inhibit hepatocellular carcinoma cells growth with the IC50of 5.6 μmol·L-1, and GRN A combined with cisplatin synergistically inhibit hepatocellular carcinoma proliferation, with the CI<1.The colony-formation assay showed that GRN A significantly enhanced the inhibitory effects of cisplatin on cellular anchorage-independent growth. Flow cytometry showed that GRN A combined with cisplatin synergistically induced apoptosis,with the apoptotic rates of 5.87%,32.74%,35.67% and 67.15% in control, GRN A, Cisplatin, and combination of GRN A and Cisplatin groups, respectively. Western blot confirmed that the two drugs synergistically changed the expressions of proteins related to apoptosis.In vivo experiment indicated that combination of GRN A and cisplatin significantly suppressed tumor growth compared with single drug treatment groups.CONCLUSION The combination of GRN A and cisplatin resulted in synergistic antitumor effects against hepatocellular carcinoma both in vitro and in vivo.

YWHAZ Binds to TRIM21 but Is Not Involved in TRIM21-stimulated Osteosarcoma Cell Proliferation / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation.</p><p><b>METHODS</b>3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened. Co-immunoprecipitation was coupled with LCMS/MS analysis to identify novel interacting partners of TRIM21. Co-immunoprecipitation and bimolecular fluorescence complementation (BIFC) were performed to validate the interactions between TRIM21 and its novel partner YWHAZ. A TRIM21-ΔRING construct was generated to test the effects of TRIM21 ligase activity on YWHAZ.</p><p><b>RESULTS</b>TRIM21 positively regulated osteosarcoma cell proliferation. Overexpression of TRIM21 enhanced osteosarcoma cell tolerance toward various stresses. YWHAZ protein was identified as a novel interacting partner of TRIM21 and its expression levels were negatively regulated by TRIM21. The RING domain of TRIM21 was required for TRIM21 negative regulation of YWHAZ expression. However, overexpression of YWHAZ did not affect positive regulation of osteosarcoma cell proliferation by TRIM21.</p><p><b>CONCLUSION</b>Our results further clarify the molecular mechanisms underlying the pathogenesis of osteosarcoma.</p>

Impact of body mass index on mortality in patients undergoing elective percutaneous coronary intervention / 中国介入心脏病学杂志

Objective To investigate the influence of body mass index(BMI) on the prognosis of patients who had received elective PCI.Methods The study population consisted of 2964 consecutive patients with electivePCIs performed between July 2009 and September 2011. The patients were divided into three groups based on their preoperative BMI levels:the normal group( BMI<24.0 kg/m2,n=810); the overweight group( 24.0 kg/m2≤BMI<28.0 kg/m2,n=1454) and the obese group(BMI≥28.0 kg/m2,n=700). We examined the association between baseline BMI levels and postoperative mortality through a mean(571.5±130.8)days of follow up.Results Patients with high BMI had a higher percentage of comorbidities compared with the normal BMI group. The results of multivariate Cox regression analysis revealed that preoperative BMI was inversely associated with mortality after adjustment for other factors (HR 0.896,95％ CI 0.821-0.977,P=0.031). Compared with the obese group, the hazard ratios for risk of mortality in the overweight and the normal groups were 1.908(95％CI 0.689-5.291,P=0.213) and 2.241(95％CI 1.154-4.350,P=0.017).Conclusions For patients undergoing elective PCI, individuals with obesity and overweight had the better prognosis than those with normal BMI.