Objective To investigate the pharmacokinetics of intravenously infused domestic alfentanil in the patients undergoing general anesthesia.Methods Twelve American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 18-47 yr,weighing 49-86 kg,scheduled for elective subtotal thyroidectomy under general anesthesia,were enrolled in the study.Anesthesia was induced with iv midazolam 0.02 mg/kg,alfentanil 25 μg/kg,propofol 1.5 mg/kg and rocuronium 0.8 mg/kg.The patients were endotracheally intubated and mechanically ventilated.Anesthesia was maintained with inhalation of 0.8％-2.0％ sevoflurane,iv infusion of alfentanil 1 μg · kg-1 · min-1,and intermittent iv boluses of rocuronium 10-20 mg,bispectral index value was maintained at 40-60,and infusion was stopped at 10 min before the end of surgery.Before induction of anesthesia,at 1,3,5,8,10,14,20,35,65,95 and 125 min ofalfentanil infusion,and at 5,15,30,60,120,180,240,300 and 360 min after termination of alfentanil infusion,venous blood samples were collected for determination of the plasma concentration of alfentanil (by high performance liquid chromatography-mass spectrometry/mass spectrometry).DAS 3.0 software was used to analyze the pharmacokinetic parameters of alfentanil.Results The pharmacokinetics of domestic alfentanil was best described by a two-compartment pharmacokinetic model.The distribution half-life was (1.8 ± 0.8) min,and the elimination half-life was (91±22) min.The volume of distribution at steady state was (0.38±0.12) L/kg,and the clearance was (4.3± 1.6) ml · kg-1 · min-1.The elimination of domestic alfentanil followed the first-order kinetics.Conclusion The distribution of intravenously infused domestic alfentanil is fitted to a two-compartment pharmacokinetic model with elimination following the first-order kinetics in the patients undergoing general anesthesia.

Objective To evaluate the application of high-performance liquid chromatography (HPLC) in diagnosis and screening of thalassemia. Methods Automated HPLC was used to measure HbF and HbA2 in 100 genetically diagnosed thalas-semic patients and 35 normal children. The results were compared with those from traditional tests including alkali denaturation test and cellulose acetate electrophoresis. The diagnose accordance rates, sensitivity and specificity were compared. Results Seventy-fourβthalassemia, 64 were heterozygous with single mutations and 10 were compound heterozygous with double muta-tions. Twenty-sixαthalassemia, 25 were compound mutations and one was heterozygous with single mutation. The HbF percent-age from HPLC was higher than that from alkali denaturation tests in either thalassemia or normal children (P<0.01). HbF level from HPLC inα-thalassemia was signiifcantly different from that in the normal children (P=0.011). The percentage of HbA2 from HPLC was higher than that from cellulose acetate electrophoresis (P=0.010). HbA2 in the single heterozygousβ-thalassemia were twice higher than that in the double heterozygous mutatedβ-thalassemia (P<0.01). The combination of HbF-HbA2 (≥4.0%) from HPLC with MCV (<80 lf) and MCH (<27 pg) had high accordance rates (99.3%), sensitivity (99.0%) and speciifcity (100.0%) in diagnosis of thalassemia. Conclusions When the results of HPLC are combined with MCV and MCH, it can be applied to the diagnosis of thalassemia with high speciifcity, high sensitivity and has high diagnostic accordance rate with genetic results. HPLC can be an ideal approach to screenβthalassemia.

Objective:To investigate the expression of HIF-1α, HIF-2αand MT in human papillary thyroid carcinoma ( PTC) and the association of their expression with clinicopathological indicators .Methods:Immunohistochemistry was used to analyze the ex-pression of HIF-1α, HIF-2αand MT in 70 PTC samples .The correlations of HIF-1α, HIF-2αand MT expression with one another , and with several clinicopathological indicators were statistically analyzed .Results:In 70 PTC samples, the positive expression rates of HIF-1α, HIF-2αand MT were 52.86%(37/70), 50.00%(35/70) and 44.29%(31/70), respectively.HIF-1α, HIF-2αand MT expression had significant correlations with cervical lymph node metastasis (P=0.034, P=0.022, and P=0.032, respectively). Meanwhile, HIF-1αexpression had a positive correlation with HIF-2α(rs =0.258, P=0.031) and MT (rs =0.266, P=0.026). HIF-2αand MT expression were positively correlated (rs=0.259, P=0.030).Concomitant expression of any two or all of the three molecules had stronger correlation with lymph node metastasis than did each alone ( P=0.004 for HIF-1α/HIF-2α, P=0.024 for HIF-1α/MT, P=0.029 for HIF-2α/MT, P=0.017 for HIF-1α/HIF-2α/MT).Conclusion:HIF-1α, HIF-2αand MT expression in PTC samples have a closely correlation , which are related to cervical lymph node metastasis .Therefore, the expression of HIF-1α, HIF-2αand MT might be used as biomarkers for cervical lymph node metastasis of PTC .

Purpose To investigate the clinical application of iodine concentration using dual-energy contrast enhanced CT in distinguishing malignant from benign thyroid nodules. Materials and Methods Patients with a total of 90 pathology proven thyroid nodules (60 malignant, 30 benign) underwent dual-energy contrast enhanced CT scanning. The iodine concentration and CT value were measured in arterial phase and venous phase, then the normalized iodine concentration (NICnod) and the normalized CT value were calculated. All results were compared in each groups, while morphology and capsule of these nodules on iodine image were analyzed. Results The morphology and capsule of nodules on iodine image were significantly different between benign and malignant nodules (Z=- 4.55, P<0.05). On iodine image, the sensitivity of partial capsule diagnosing malignant nodules was 78.33% with specificity of 66.67%. The NICnod and normalized CT value for normal group, benign group and malignant group showed significant differences in arterial phase and venous phase (F=36.87-69.89, P<0.05); the NICnod and normalized CT value between benign group and malignant group showed statistic difference in arterial phase (Z=- 3.48- -2.33, P<0.05), and those among normal group, benign group and malignant group also showed statistic differences (Z= -7.01- - 4.87, P<0.05). NICnod had significant correlation with normalized CT value in each phases (r=0.89, 0.74 and 0.75, P<0.05). When using NICnod and normalized CT value of 0.76 and 0.79 to differentiate malignant thyroid nodules, the area under ROC curve values were 0.91 and 0.92. NIC and normalized CT value showed a good consistency with iodine map in venous phase (Kappa=0.762 and 0.768), Combining morphology and capsule of nodules on iodine image, the sensitivity was 90.01% and the specificity was 93.60%. Conclusion Iodine concentration with dual-energy contrast enhanced CT scanning can differentiate malignant from benign thyroid nodules; combining morphology and capsule of nodules improves the accuracy of diagnosis.

Objective To evaluate the inhibitory effect of asiaticoside on bleomycin-induced skin cicatrization. Methods Thirty male C57BL/6 mice were randomly divided into three groups:negative control group,model control group,and asiaticoside group,ten in each group.In model control group and asiaticoside group,1 mg·mL-1bleomycin was subcutaneously injected into the dorsal skin of mice every day;4 h later,1 mL 0.9% sodium chloride solution 1 mL asiaticoside(20 mg·mL-1) was injected into the lesion skin in the model control group and the asiaticoside group,respectively.In the negative control group, the same volume of 0.9% sodium chloride solution was subcutaneously injected into the dorsal skin of the mice at the two time points every day.After 21 days,skin specimens were harvested to observe the histomorphology and detect myofibroblast proliferation and expression of inflammatory factors. Results The skin scar was significantly attenuated in the asiaticoside group as compared with the model control group,and the dermal thickness measured exhibited a gradual decrease in asiaticoside group.The expression of α-antismooth muscle antisbidy and infiltration of inflammatory cells were significantly lower in the asiaticoside group than in the model control group. Conclusion Asiaticoside inhibits the development of skin scar of mice by regulating proliferation and differentiation of myofibroblasts and down-regulating inflammatory cells.

Objective:To explore effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on macrophage M1/M2 polarization.Methods:hUC-MSCs were co-cultured with pTHP-1 cells which were macrophage-like cells induced by PMA and tran-scriptome sequencing data were analyzed.Differentially expressed genes were screened and analyzed by GO and KEGG enrichment analysis.Effect of hUC-MSCs on pTHP-1 cells proliferation was analyzed by cell proliferation assay(CCK-8 and EdU).Flow cytometry was used to verify influence of hUC-MSCs on relative contents of inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 in pTHP-1 cells which were interaction with LPS.Effect of hUC-MSCs on M1/M2-related molecular phenotype of pTHP-1 cells was studied by qRT-PCR and flow cytometry.Results:Transcriptome sequencing data analysis showed that M1-related genes TNF-α(P<0.05)and HLA-DRA(P<0.01)decreased to a great extent and M2-related gene ARG1(P<0.05)increased to a great extent in pTHP-1 cells after co-culture with hUC-MSCs,suggesting that hUC-MSCs inhibited macrophage M1 polarization.GO and KEGG analysis showed that these dysregulated genes regulated inflammation and immune response.hUC-MSCs inhibited proliferation of pTHP-1 cells,reduced content of TNF-α and increased content of IL-10(P<0.001).qRT-PCR and flow cytometry showed mRNA expressions of HLA-DRA(P<0.05)and CD68(P<0.01)and CD14+CD11c+M1 macrophage percentage were down-regulated,while mRNA expressions of CD163(P<0.001),CD206(P<0.001)and CD14+CD163+M2 macrophage percentage were significantly up-regulated in pTHP-1 cells after co-culture with hUC-MSCs.Conclusion:hUC-MSCs inhibit macrophage polarization to M1 and promote polariza-tion to M2 in vitro.

The treatment rules of point selection and treatment principles for treating chronic fatigue syndrome (CFS) can be divided into three categories: regulating and replenishing, invigorating original yang and regulating zang-fu organs. The mechanism of moxibustion includes improving gut microbiota imbalance, regulating immune cell imbalance and correcting endocrine dysfunction. The moxibustion methods include ginger-partitioned moxibustion, thunder-fire moxibustion, warm acupuncture, and governor moxibustion. Acupuncture points such as Shenque (RN8), Guanyuan (RN4), Qihai (RN6), Zusanli (ST36), Baihui (DU20), Yongquan (KI1) and back-shu points are often selected to exert anti-chronic fatigue effects.

Objective:To observe the therapeutic efficacy and prognosis of daratumumab combined with chemotherapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) followed by daratumumab and lenalidomide maintenance treatment for primary plasma cell leukemia (PCL).Methods:The clinical data of a patient with primary PCL admitted to the First People's Hospital of Yunnan Province in January 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:The patient was diagnosed with primary PCL and treated with daratumumab combined with BD (bortezomib + dexamethasone) for 1 course and BCDD (bortezomib + cyclophosphamide + liposomaldoxorubicin + dexamethasone) for two courses. The patient was treated with daratumumab combined with allo-HSCT after complete remission. The donor cells were successfully implanted and the chimerism rate of donor cells was 94.36% without acute graft-versus-host disease reaction. And then the patient received intermittent maintenance therapy of daratumumab combined with low dose lenalidomide after transplantation, and the current remission period after transplantation reached 4 months.Conclusions:Daratumumab combined with chemotherapy bridging to allo-HSCT followed by daratumumab and lenalidomide may improve the prognosis of primary PCL and prolong survival time.

Hepatocellular carcinoma (HCC) is a common malignant tumor of the liver characterized by a high incidence rate, rapid progression, and poor prognosis. In recent years, it has been found that non-coding RNA (ncRNA) participates in the regulation of tumor immunity in tumor microenvironment (TME) and in turn affects the biological behavior of HCC. This article briefly describes the regulatory effect of ncRNA on immune cells in TME and introduces the potential value of ncRNA in the diagnosis and treatment of HCC, in order to provide potential diagnostic and treatment strategies for HCC.

Objective To explore the pathogenesis of Russell-Silver syndrome (RSS). Methods Two milliliter peripheral blood samples were collected from 6 male patients aged 6 to 8 years with suspected RSS phenotype, the parents of 2 patients and 5 healthy boys. Mononuclear cells were isolated and genomic DNA was extracted. The methylation level of the H19 imprinting control region(ICR)1 on chromosome 11p15.5 was detected by pyrosequencing.The methylation status and the copy number variation in the corresponding region of one RSS patient with positive results by pyrosequencing were analysed by methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA). Results Pyrosequencing analysis revealed that the methylation rates on the 6 CpG targeting sites in H19 differentially methylated region(DMR)in the 6 RSS patients were about 11%~29%, which were significantly lower than those in their parents and normal controls (44%~59%). The MS-MLPA results of one patient with positive pyrosequencing showed that the methylation rates of 4 sites in H19-DMR were about 10%,which was obviously lower than the normal level.The methylation rates of the 4 sites in KCNQ1OT1 gene were about 50%, which was in the normal range. The copy number variations from all samples detected were in the normal range. Conclusion There is methylation aberration of H19-DMR in ICR1 in children with RSS.