Objective:To explore the genotypes and clinical phenotypes of three families with Liddle Syndrome(LS).Methods:In this study, three young patients with hypertension and hypokalemia were confirmed LS through second-generation sequencing genetic testing. Members of the three families were screened for genes, and genotypes and clinical phenotypes were analyzed.Results:This study identified three patients in Family 1 carrying a possible pathogenic heterozygous variant c. 1859A>G(p.Y620C) in the SCNN1B gene(sodium channel epithelia 1β subunit). Five patients in family 2 and family 3 carried the pathogenic heterozygous variant c. 1789dup(p.R597Pfs*11) in the SCNN1B gene. Following three months of treatment with salt restriction and triamterene, blood pressure and potassium levels returned to normal in all eight patients.Conclusion:LS patients typically present clinically with early-onset hypertension accompanied by hypokalemia, but there is clinical heterogeneity. It is recommended to conduct genetic testing on suspected patients as early as possible to confirm the diagnosis and initiate timely treatment with effective medications so as to reduce the complications of target organs.

OBJECTIVE: To establish a method for directional screening of the cytotoxic components from the medicinal herb of Achnatherum inebrians by a combination of surface plasmon resonance (SPR) biosensor and chromatographic isolation technology. METHODS: Under the guidance of bioactive assessment based on binding abilities between objects and the α-Mannosidase (α-Man) target, the active components from different solvents extracts, different polar extraction parts and fractions were screened orderly and directionally using SPR. Components with a high binding ability to α-Man can be precisely oriented in a narrower fractions range and are easy to isolate. Three human cancer cells were used to evaluate the cytotoxic activity of component with the highest affinity to α-Man. RESULTS: Eight compounds were isolated and identificated from A. inebrians for the first time. Deoxyvasicinone possessed the highest affinity to α-Man among them. Moreover, deoxyvasicinone showed good effects on inhibited proliferation of human hepatoma cells HepG2 (IC₅₀ = 5.7 μmol/L), human breast cancer cells MCF7 (IC₅₀ = 7.21 μmol/L) and human lung cancer cells HCC827 (IC₅₀ = 0.75 μmol/L), respectively. In particular, its inhibitory effect on HCC827 was stronger than the positive drug gefitinib (IC₅₀ = 1.65 μmol/L). CONCLUSION A comprehensive strategy of directional screening potential cytotoxic components from herb based on biomolecular interaction and chromatography was established. Deoxyvasicinone as an effective anti-cancer component was initially isolated from A. inebrians. It is expected that this screening strategy could provide new perspectives for rapid screening and identification of active components from natural plants with the complex matrix.

Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.
COVID-19 ; Disease Outbreaks/prevention & control* ; Humans ; Monkeypox/epidemiology* ; Monkeypox virus ; Pandemics/prevention & control*

【Objective】 To provide reference for formulating relatively unified quality control strategies and meeting the requirements of homogenization construction of blood banks across Chongqing area by retrospectively analyzing sampling results of different blood components during the past two years in all levels of blood banks in Chongqing area. 【Methods】 The key quality data of blood components prepared by 6 blood banks in Chongqing were analyzed retrospectively. According to the issuing units to the clinical during the past two years, the research objects were selected as leukocyte-depleted suspended RBCs, cryoprecipitate, pathogen inactivated fresh frozen plasma(FFP) and apheresis platelets. The quality data of the above-mentioned blood components from January 2019 to June 2021 were collected and analyzed. 【Results】 For leukocyte-depleted suspended RBCs(1U)prepared by 5 blood banks, statistically significant differences in Hb, residual white blood cells and hemolysis rate at the end of storage, except for Hct, were noticed(P<0.05). For cryoprecipitate, the content of blood coagulation factor Ⅷ and fibrinogen were statistically different among 3 blood banks in 1U specification(P<0.05) and among 5 blood banks in 2U specification(P<0.05). For pathogen inactivated FFP, the content of blood coagulation factor Ⅷ, plasma proteins, and residual methylene blue were statistically different among 3 blood banks(P<0.05). For apheresis platelets, Plt, white/red blood cells contamination and pH at the end of storage were statistically different among 3 blood banks(P<0.05). 【Conclusion】 The quality data of blood components, prepared by different blood banks, meet the requirements of national standard, however, certain differences are existing among blood banks.Key points during the process of collection, preparation, storage and transportation need to be cleared and unified, so as to reduce the differences between each other, and determine the direction and basis for homogeneity construction in the next step.

Objective To investigate the role of BRAFV600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results. Methods This study included 9837 patients who underwent US-FNA. We mainly analyzed 239 cases with benign or indeterminate cytology, but having a detection of BRAFV600E muta-tion. BRAFV600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction. Results In 93 nodules with benign cytology results but positive BRAFV600E mutation, 84 nodules were malignant. Based on the results, US-FNA combined with BRAFV600E mutation analysis will improve sensitivity (Se=94.03％)and negative predictive value (NPV=2.69％) of the thyroid nodules diagnosis than using US-FNA alone(Se=71.03％, NPV=20.76％). Conclusion BRAFV600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV. When facing patients with benign or indeterminate cytology but positive BRAFV600E mutation, thyroidectomy should be considered.

Objective: To investigate the role of BRAF^V600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results. Methods: This study included 9837 patients who underwent US-FNA. We mainly analyzed 239 cases with benign or indeterminate cytology, but having a detection of BRAF^V600E mutation. BRAF^V600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction. Results: In 93 nodules with benign cytology results but positive BRAF^V600E mutation, 84 nodules were malignant. Based on the results, US-FNA combined with BRAF^V600E mutation analysis will improve sensitivity (Se=94.03%) and negative predictive value (NPV=2.69%) of the thyroid nodules diagnosis than using US-FNA alone (Se=71.03%, NPV=20.76%) . Conclusion BRAF^V600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV. When facing patients with benign or indeterminate cytology but positive BRAF^V600E mutation, thyroidectomy should be considered.

Aim To synthesize 8-bromo-ethoxy Rhein and investigate its mechanisms and inhibition effect on hepatitis B surface antigen ( HBsAg ) and e antigen ( HBeAg) in HepG2.2.15 cells.Methods 8-bromo-ethoxy Rhein was synthesized based on the chemical structure of Rhein , and its structure was identified by IR,1 H-NMR and 13 C-NMR spectra.MTT assay was used to test the inhibitory effect of 8-bromo-ethoxy Rhein on HepG2.2.15 cells.After the cells treatment by 8-bromo-ethoxy Rhein , the HBsAg and HBeAg in cell supernatant were detected by ELISA .The expres-sion of hepatitis B virus X gene ( HBx) was detected by Western blot .The cell cycles were examined with flow cytometry.The intracellular free calcium concentration was detected by laser scanning confocal microscopy . Results The structure of 8-bromo-ethoxy Rhein was confirmed by IR,1 H-NMR and 13 C-NMR.MTT results showed that synthetic product and Rhein could inhibit the cell proliferation in HepG2.2.15 cells.After trea-ted with 8-bromo-ethoxy Rhein and Rhein for 72 h,the half inhibitory concentration 50%( IC50 ) was 14.29 mg? L-1 and 11.59 mg? L-1 , respectively .Using non-cytotoxic dose of 8-bromo-ethoxy Rhein , the inhibitory effect on HBsAg and HBeAg was gradually enhanced with increasing 8-bromo-ethoxy Rhein concentration . The inhibitory effect of synthetic product on hepatitis B virus was better than that of Rhein .8-bromo-ethoxy Rhein could down-regulate the expression of HBx , in-tracellular calcium ion concentration and block the hepatitis B virus ( HBV ) replication.Flow cytometry results showed 8-bromo-ethoxy Rhein didn′t affect the cell cycle .Conclusions Compare with Rhein , the synthesis of 8-bromo-ethoxy Rhein shows stronger inhi-bition on hepatitis B virus in HepG2.2.15, and its mechanisms may involve down-regulating the expres-sion of HBx and reducing calcium ion concentration .

The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angio-genesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 ? 1) among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after 131I-Kringle 5 was injected, 131I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder. The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker 131I-Kringle 5 and SPECT/CT were suc-cessfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of 131I-Kringle 5.

Objective To investigate the efficiency of biology function of ITIH4 gene silenced by small interfering RNA (siRNA) on ovarian cancer.Methods The four pairs ITIH4 gene siRNA interference fragments(ITIH4-546,ITIH4-795,ITIH4-917 and ITIH4-1568) were designed respectively,and transfected into HO8910pm cells with ITIH4 mRNA high expression by liposomal method transiently.Quantitative PCR method was used to detect the ITIH4 mRNA expression in HO8910pm cells transfected with interference fragment.The ITIH4 917 was selected as the best silencing effect of siRNA interference fragment and then the recombinant plasmid expression vector pGPU6/GFP/Neo-shRNA-ITIH4-917 was constructed and transfected into HO8910pm cells.The stably transfected cells-pGPU6/GFP/Neo-shRNA-ITIH4-917-HO8910pm cells was obtained by screening of aminoglycoside antibiotics (G418).The experiment was divided into three groups,namely ITIH4-917 transfection group,the HO8910pm cell group transfected with pGPU6/GFP/Neo-shRNA plasmid (empty vector group),and the HO8910pm cell group transfected with pGPU6/GFP/Neo-shRNA-ITIH4-NC the plasmid (negative control group).Fluorescence quantitative reverse transcription(RT)PCR and western blot were used to detect the ITIH4 mRNA and protein expression.The cell proliferation,the cell cycle,colony formation of cells,cells migration and invasion in vitro were determined by using methyl thiazolyl tetrazolium (MTT),flow cytometry,colony formation assay and transmembrane (transwell) small chamber method [value represented by absorbance (A)],respectively.Results The fluorescent quantitative PCR results showed that the ITIH4 mRNA expression levels in ITIH4-917 HO8910pm cells was significantly lower than that in the control cells,the relative copy number was only 0.26 ± 0.15.Also the relative copy number of ITIH4 mRNA in ITIH4-917 transfection group cells was 0.34 ±0.10,it significantly lower than that in empty vector group (1.87 ±0.12,P =0.008) and negative control group (1.58 ±0.21,P =0.032) ; Western blot results showed that the ITIH4 relative expression levels of the protein in ITIH4-917 HO8910pm group cells,empty vector group and negative control group were 0.51,1.64 and 1.74,respectively,there were statistically significant differences (0.51 vs.1.64,P =0.012; 0.51 vs.1.74,P =0.014).MTT colorimetric assay showed that the proliferation of ITIH4-917 HO8910pm group cells was significantly faster than that in the empty vector group and negative control group,and there were statistically significant differences among them (P =0.001).The S ± G2/M phase cell ratio in ITIH4-917 HO8910pm group cells was 54.2％,which was significantly higher than that in the empty vector group or negative control group (26.3％ and 31.3％,respectively,all P ＜ 0.05).The colony formation rate (55.7 ± O.7) ％ in ITIH4-917 HO8910pm group cells was also significantly higher than that in empty vector group (29.7 ±0.9) ％ (P =0.037) and negative control group (31.4 ± 0.3) ％ (P =0.043).Migration and invasion experiments showed that cell migration in ITIH4-917 HO8910pm group cells was 0.40 ± 0.18,whicht was significantly higher than that in the negative control group or empty vector (0.30 ±0.03,P =0.031 ;0.25 ±0.03,P =0.028,respectively).Although the invasive ability of ITIH4-917 HO8910pm group cells (1.31 ±0.34) was higher than that in the control cells (1.05 ±0.68) and empty vector group (1.14 ±0.08),while there were not significant difference (P ＞ 0.05).Conclusion It would be to promote the cell doubling time and increase the migration capability in HO8910pm cells that ITIH4 expression was down-regulating by ITIH4 mRNA interference.