Risk factors of supplementary injection after foam sclerotherapy for varicose veins of lower extremities and its impact on blood coagulation function / 实用医学杂志

Objective To explore the risk factors of supplementary injection after foam sclerotherapy for varicose veins of lower extremities and its impact on blood coagulation function.Methods A total of 185 patients with varicose veins of lower limbs diagnosed in the First People's Hospital of Zunyi from January 2018 to December 2021 were selected.The corresponding pathological data were collected,and the D-dimer,thrombin time,and fibrinogen level of patients were detected 1 d before and 1 d after the surgery.The postoperative video phone follow-up lasted until 6 months after the surgery.The patients were divided into single treatment group and supple-mentary treatment group according to whether supplementary injection of foam sclerosing agent was needed during the follow-up.Propensity matching on the data between the two groups was conducted,and the correlation between disease course data,coagulation factors,and the occurrence of supplementary injection was analyzed.A time series model for the incidence of supplementary injection was established,and the therapeutic effect and complica-tions were observed.Results After propensity matching,there was still significant difference in the degree of lesion between the two groups(P<0.05).On the first day after surgery,there was significant difference in the D-dimer and fibrinogen groups between the two groups(P<0.05),and but no significant difference in thrombin time(P>0.05).The occurrence of supplementary injection was significantly correlated with D-dimer,fibrinogen,thrombin time,and first-time injection dose(P<0.05),and the incidence of supplementary injection was higher in patients who received first-time injection in January,August,September,and December.Both groups achieved successful treatment 6 months after surgery,and there was no significant difference in the incidence of compli-cations.Conclusion Patients with lower limb varicose veins of C3/C4 are more likely to require supplementary injection compared to patients with other levels.The level of D-dimer and fibrinogen at 1 d after surgery is positively correlated with the occurrence of supplementary injection,while the dose of the first injection is negatively corre-lated with the occurrence of supplementary injection.

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System / 神经科学通报·英文版

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

Effects of keto acid supplements on Chinese patients receiving maintenance hemodialysis: a prospective, randomized, controlled, single-center clinical study / 中华医学杂志(英文版)

BACKGROUND@#The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition.@*METHODS@#This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients' nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.@*RESULTS@#The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study.@*CONCLUSIONS@#In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients' mineral metabolism, inflammatory parameters, or body compositions.

Synthesis, biological activity, computer aided drug design of alpha-pinene derivatives / 中国中药杂志

Based on the anticancer mechanism of biological alkylating agent, we designed and synthesized two alpha pinene derivatives:(1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl benzenesulfonate and (1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl 4-methylbenzenesulfonate, of which structures were confirmed by ¹H-NMR, HPLC and MS date. These two compounds showed a good inhibition of tumor cells' proliferation. Further, the computer siuulation of molecular docking and metabolic kinetics indicated that these two copounds may have stable molecular complexation with protein CDK2, which closely related to the cell cycle.

Effects of α-pinene extracted from pine needle on expression of miR-221 and its potential target genes in human hepatocellular carcinoma cells / 中国中药杂志

To investigate the anti-hepatoma mechanism of α-pinene, HepG2 cell was treated with α-pinene and the change of cell cycle was examined by flow cytometry. The expression of miR-221, which was related the regulation of G₂/M phase, was detected by quantitative Real-time PCR. Meanwhile, TargetScan and other online bioinformatics methods were used to analyze and predict the target genes of miR-221, then the expression level of related target genes were detected by quantitative Real-time PCR. The results showed that α-pinene inhibited the proliferation of HepG2 cells in dose-dependent manner. It was also proved that HepG2 cells were arrested at G₂/M phase by α-pinene (P<0.05). The expression of miR-221 was down-regulated in α-pinene treated HepG2 cell. The bioinformatics analysis showed that CDKN1B/P27 and CDKN1C/P57 may be the protential targets of miR-221 and both of them were significantly up-regulated（P<0.001,P<0.05）by α-pinene treatment. According to these results, it was believed that α-pinene may inhibit the proliferation of hepatocellular carcinoma cells through arrest the cell at G₂/M phase, which may be associated with the down-regulate of the miR-221 expression and up-regulate of the CDKN1B/P27 and CDKN1C/P57 expression.

Activated changes of platelet ultra microstructure and plasma granule membrane protein 140 in patients with non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Platelet activation may play an important role in pathologic progress in lung cancer. In this study, we aimed to clarify the influence of activated platelets on lung cancer generation and growth, and the relationship among these functional and ultrastructural changes of platelets and the severity of pathogenetic condition in these patients with NSCLC.</p><p><b>METHODS</b>One hundred and thirty-six cases of patients with pathologically confirmed NSCLC were included in this study. Fifty-four healthy people were enrolled as controls. The change of ultra microstructure and activity of blood platelets were observed under the transmission and scanning electron microscope. Simultaneous determination of plasma granule membrane protein 140 (GMP-140) was made.</p><p><b>RESULTS</b>Transmission electron microscopy showed remarkable changes of ultra microstructure of platelets in patients with NSCLC, including swelling, increase of a-granules, vesicles, and glycogenosome. Scanning electron microscopy showed many more surface processes and wrinkles on platelets in patients with NSCLC. The reference plasma levels of GMP-140 of healthy controls were (18.2 +/- 2.7) microg/L. The plasma levels of GMP-140 in patients with NSCLC were (47.8 +/- 12.3) microg/L, which were much higher than those of the controls. There was a medium positive correlation between plasma levels of GMP-140 and amount of a-granules (r = 0.514, P < 0.01) and a high positive correlation between plasma levels of GMP-140 and area of platelet (r = 0.84, P < 0.01) in patients with NSCLC. The Kaplan-Meier survival curve analysis showed significant shift to the left in patients with NSCLC whose a-granules per platelet were 19 or more compared to those 18 or less (Log rank statistic, chi(2) = 17.38, P < 0.01).</p><p><b>CONCLUSIONS</b>There are significant activated changes of ultra microstructure and increased activity of blood platelets in patients with NSCLC. These activated platelets may play an important role in the generation and growth of lung cancer. These changes can be used as a diagnostic index of severity, progression, and prognosis of NSCLC.</p>