Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objectives To provide scientific basis for the quality control of different species of Baishouwu by establishing the HPLC fingerprint of domestic of Baishouwu and determining the main active components of acetophenones. Methods HPLC-DAD method was used to determine the HPLC fingerprints of domestic of Baishouwu. Then, the content of 4 kinds of acetophenones in Baishouwu was determined. The column was Diamonsil C₁₈（250mm×4.6mm, 5μm）with the mobile phase of methanol and 0.1% phosphoric acid at a flow rate of 1.0 ml/min. The detection wavelength of p-Hydroxyl acetophenone, baishouwu benzophenone, 2',4'-Dihydroxy acetophenone was set at 260 nm and 2',5'-Dihydroxy acetophenone at 280 nm respectively. Results The similarity and cluster analysis in HPLC fingerprint showed that the constituents were significantly different among C. bungei, C. auriculatum and C. wilfordii. The content of total acetophenones in C. wilfordii was significantly higher than that in other localities of C. auriculatum and C. bungei. Conclusions Acetophenone could be used as the evaluation index to evaluate the quality of Baishouwu in different origins. The content of total acetophenone in C. wilfordii is the highest, which could be used as the best quality resource of Baishouwu.

Radiation-induced brain injury (RBI) is one of the complications after radiotherapy for head and neck malignant tumors, which seriously affects the quality of life of patients. The pathophysiological mechanism of RBI is not completely clear. Current studies suggest that it is involved in a variety of cells in the central nervous system (CNS), whereas astrocyte, as the largest number of glial cells in the CNS, plays an important role in maintaining the CNS homeostasis and responding to CNS injury. In this article, the role of astrocytes in RBI was reviewed.

Objective:To investigate the efficacy and safety of three-dimensional navigation template assisted osteotomy for fracture malunion of lateral condyle of humerus in children.Methods:Eighteen children with ma-lunion of fracture of lateral condyle of humerus were treated in Southern Medical University Third Affiliated Hospital from August 2012 to December 2019 and analyzed retrospectively.Among them, 12 cases were treated with routine ope-ration: according to CT reconstruction and empirical osteotomy during the operation, the location of deformity was analyzed.Six cases were treated with navigation template assisted osteotomy: according to the CT data of bilateral elbow joints, a three-dimensional bone model was established, and the coronal and sagittal deformities of the distal humerus were evaluated by comparing the images of the distal humerus of the affected side with the distal humerus of the healthy side, so as to determine the best plane of osteotomy and the target position of reduction.The preoperative simulation was carried out on the computer, and the osteotomy navigation template and reduction navigation template were designed.The navigation template was printed out with a 3D printer.During the operation, the osteotomy was corrected with the assistance of navigation template, and the broken end of osteotomy was fixed with hollow screw and fixed with 80 degree flexion plaster.The X-ray films of the two groups were reexamined regularly after operation.The amount of intraoperative blood loss, operation time, incidence of postoperative complications (necrosis of humeral head and trochlea, delayed ulnar nerve paralysis, and bone nonunion) and the recovery of flexion and the extension function of elbow joint were observed in the 2 groups.Results:The elbow joint activity of all children basically returned to normal, the orthopedic site of osteotomy achieved bony healing, and the orthopedic effects were satisfactory.All the 18 cases were followed up for 6-24 months (mean 15 months). According to the postoperative Dhillon score, the navigation template group was excellent in 1 case and better in 5 cases, while in the routine group, 11 cases were batter and 1 case was fair.There were no significant differences in Dhillon score between the 2 groups after operation ( P>0.05). There were no significant differences in the range of the motion of elbow joint between the 2 groups ( P>0.05). In the comparison of operation time and intraoperative blood loss, the navigation template group [(200.0±24.2) min, (85.0±10.9) mL]was better than the routine group[(232.0±20.1) min, (139.1±18.3) mL](all P<0.001). Conclusions:The application of three-dimensional humerus reconstruction and mirror image contrast to evaluate the distal humerus deformity of the affected side, and the design of osteotomy and reduction navigation template auxiliary operation can restore the normal anatomical structure of elbow joint to the greatest extent.Accurate correction, and the function of elbow joint recover well after operation, which optimizes the operation procedure, improves the safety and effectiveness of the operation.

Objective : To construct an appropriate technology catalogue for general practice based on Delphi method,and to provide reference for promoting appropriate techniques and training general practitioners. Methods : The catalogue was briefly constructed based on literature reviews and the data of the top twenty diseases diagnosed in out-patient department of Sir Run Run Shaw Hospital and two community health service centers in Hangzhou. Two-round Delphi consultation was conducted by fourteen general practitioners coming from upper first-class hospitals and community hospitals. The final catalogue was established according to evaluation of the degree of involvement,authority coefficient and Kendall's W values of the fourteen specialists. consultations : Results Of the fourteen specialists,nine had bachelor's degrees and five had master's degrees or above;twelve were deputy chief physicians or chief physicians and two were physicians. They were engaged in general practice for 17.21 years in average. The positive coefficients of the two rounds of were both 100.00%. The authority coefficient of the specialists was 0.891. After the first round of consultation,the W values for importance and feasibility of 6 first-class indicators were 0.170 and 0.244,and the ones of 56 second-class indicators were 0.236 and 0.250（all P<0.05）. Six of second-class indicators were excluded because their coefficent of variation（CV）for importance and feasibility were more than 0.25. After the second round of consultation,the W values for importance and feasibility of 6 first-class indicators were 0.245 and 0.247,and the ones of 50 second-class indicators were 0.355 and 0.370（all P<0.05）. The CV for each indicator was less than 0.25. Finally,an instructional catalogue was defined,consisting of 6 first-class indicators（basic diagnosis and treatment skills,first aid skills,symptomatic diagnosis and treatment skills,chronic disease management skills,common disease diagnosis and treatment skills,and common manipulative skills）and 50 second-class indicators. Conclusion The degrees of involvement,authority and consistency of the specialists were relatively high. The catalogue of appropriate technology for general practitice had good reliability and feasibility,which was worthy of promotion and application.

Objective To study the association of maternal calcium supplementation and dietary calcium intake with the preterm birth so that to provide scientific basis for effective intervention of preterm birth. Methods Normal pregnant women who were followed up all through to childbirth in Gansu Provincial Maternity and Child Care Hospital were selected. Multivariate logistic regression was used to evaluate the associ-ation of calcium supplementation and intake with preterm birth. Results After confounding factors were adjus-ted, pregnant women who took calcium supplement for more than 3 months before and/or during pregnancy had the risk of preterm birth reduced by 14% which was dose-responding ( OR=0. 86, 95% CI=0. 77-0. 96, P<0. 05). Through stratifying by trimesters of pregnancy, it was found that calcium supplement in the third trimes-ter was a protective factor for preterm birth and especially significant in early and very early pregnancy ( OR=0. 75, 95% CI=0. 62-0. 92, P<0. 05). Through stratifying by dietary calcium intake, pregnant women who took dietary calcium more than 465. 55 mg/d had the risk of preterm birth significantly reduced which was shown by the reduction of preterm birth of different degrees, controlled preterm labor and spontaneous premature dilivery (OR=0. 66, 95% CI=0. 53-0. 82, P<0. 05). Conclusion Appropriate calcium supplementation or dietary calcium intake before and during pregnancy can reduce the risk of preterm birth, which is especially sig-nificant in late pregnancy.

Objective To explore the feasibility of oxygen saturation related diffusion index for assessing oxygenation status,and to establish the critical value of the oxygen saturation related diffusion index,so as to provide more approaches to monitoring oxygenation status.Methods A total of 30 patients with acute respiratory distress syndrome (ARDS) receiving mechanical ventilation support were retrospectively reviewed.Totally 340 cases were collected at corresponding time points,and were divided into mild,moderate and severe groups according to ARDS Berlin criteria.Results There was a positive correlation between oxygen saturation related diffusion index and oxygenation index (r=0.698,P＜0.001);the critical value between the moderate and severe groups of oxygen saturation related diffusion index was 171(sensitivity 84.7％,specificity 68.2％),and the critical value between mild group and moderate group was 440 (sensitivity 56.9％,specificity 91.9％).Conclusion The oxygenation index was consistent with the oxygen saturation related diffusion index in judging the oxygenation status of ARDS patients.As a noninvasive and continuous index,the oxygen saturation related diffusion index provides a new method for nursing assessment.

Objective: To explore the association between the accumulation of metabolic syndrome (MS) components and abnormal brachial ankle pulse wave velocity (baPWV), and to investigate the effect of accumulation of abnormal metabolic components on abnormal baPWV among adult individuals undergoing routine health examination. Methods: It's a cross-sectional study. Data from 9 201 stratified sampled subjects, aged between 25 to 75 years old, who took part in the annual health checkups in 11 cities of Zhejiang Province from January to December 2016, were analyzed. Blood pressure(BP), fasting plasma glucose(FPG), waist circumference(WC), triglyceride(TG), high-density lipoprotein cholesterols(HDL-C) were defined as MS components. The baPWV was measured by VP-1000 (BP-203RPE Ⅲ) and ΔbaPWV (measured baPWV-reference baPWV/reference baPWV) ×100 (%)> 10% was defined as abnormal. The relationship between MS components and ΔbaPWV was analyzed by linear regression, and impact of accumulation of MS components on ΔbaPWV was analyzed by logistic regression, and the ΔbaPWV in subjects with different levels of MS components were analyzed by analysis of variance. Results: (1) The linear regression analysis demonstrated a positive correlation between ΔbaPWV and MS components including systolic blood pressure, diastolic blood pressure, WC, FPG, TG, while ΔbaPWV was negatively correlated with HDL-C. The β values were 0.518, 0.616, 0.208, 2.778, 1.862, -1.339, respectively (all P<0.001), indicating a strong association between ΔbaPWV and systolic blood pressure, diastolic blood pressure, and FPG. (2) The logistic regression analysis showed that the proportion of abnormal ΔbaPWV was 2.595 times higher in MS individuals than in non-MS individuals (P<0.001). Abnormal ΔbaPWV increased in proportion with increase in numbers of the metabolic components (OR=1.913, 2.884, 3.833, 6.161, 11.176 in individuals with 1,2,3,4,5 metabolic components, respectively, all P<0.001). (3) The logistic analysis suggested that each component of MS could affect baPWV,and OR was 4.68, 2.45 for systolic blood pressure and/or diastolic blood pressure and FPG. All combinations of 2 components of MS also significantly affected baPWV,and OR value was the highest (5.104(95%CI 4.281-6.085), P<0.001) for FPG+BP. All combinations of 3 components of MS significantly affected baPWV,and OR value was the highest(5.385(95%CI 4.245-6.831), P<0.001) for BP+FPG+TG. All combinations of 4 components of MS affected baPWV,and OR value was the highest (6.519(95%CI 4.731-8.984), P<0.001) for BP+FPG+WC+TG. (4) Finally, every component of MS was divided into 3 levels, their impact on abnormal ΔbaPWV was analyzed. Prevalence of abnormal ΔbaPWV significantly increased with the increasing levels of the metabolic components expect for HDL-C, the F values were 1 224.66, 832.89, 192.72, 112.79 and 56.22, respectively (all P<0.001), indicating that higher levels of metabolic components significantly affected the ΔbaPWV. Conclusions MS and accumulation of abnormal MS components are closely related with abnormal ΔbaPWV, and the combination of BP and FPG have the greatest impact on the abnormal ΔbaPWV. Analysis on the accumulation of MS components might serve as an early indicator of arteriosclerosis.

Objective: To identify the disease-causing mutations in a pedigree with familial hypertrophic cardiomyopathy (HCM) from Yunnan province, and analyze the relationship between the genotype and the phenotype. Methods: The blood samples and the clinical data of the HCM family members were collected.The coding exons and their flanking intronic regions of 28 previously reported genes related to HCM were screened in the proband by high-throughput sequencing. The mutations in proband were confirmed and detected in all family members as well as in 159 healthy controls by Sanger sequencing.The relationship between the genotype and the phenotype was analyzed in this pedigree. Results: Two missense mutations of Arg1045His and Ala26Val in β myosin heavy chain gene(MYH7) were identified. Genetic screening showed that the mother and brother of the proband carried Arg1045His mutation.Both mutations were absent in other family members and in 159 healthy controls.Disease onset age was less than 50 years old in this pedigree, chest pain, exertional dyspnea and syncope were the major symptoms, and all accompanied by severe left ventricular hypertrophy and left ventricular outflow tract stenosis.The grandma of the proband suffered sudden cardiac death. The proband had the worst symptoms and the earliest disease onset in this pedigree. Conclusions We find a pedigree with familial HCM from Yunnan province carrying MYH7 Arg1045His and Ala26Val mutations. The study suggests that Arg1045His mutation in MYH7 gene caused HCM is malignant with early onset, severe ventricular hypertrophy and poor prognosis. Arg1045His and Ala26Val double-mutant might have dosage effects and aggravate the clinical phenotype of the patient.

Objective: A new ion exchange column technology was used to establish an efficient and sensitive method for the detection of inorganic arsenic. Methods: Based on the new As Specia Fast Column, the pretreatment methods, liquid phase separation and mass spectrometry determination conditions of inorganic arsenic in rice were optimized. Finally, arsenic compounds were separated by As Specia Fast Column and detected by liquid chromatography inductively coupled plasma mass spectrometry. The external standard method was used for quantitative analysis. The detection limit, precision and accuracy of the method were determined by measuring the content of arsenic compounds in rice samples and rice standard samples. At the same time, three Guangdong rice samples were selected as the experimental samples of this study, and 1 g of each sample was weighed and measured in parallel three times. The method was compared with the method of liquid chromatography-atomic fluorescence spectrometry (LC-AFS) and liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS) in the national standard. Results: The inorganic arsenic in rice was extracted with 0.5% nitric acid solution at 65 ℃ for 15 h, and the pH was adjusted to alkaline. The mobile phase A (8 mmol/L HNO₃, 50 mmol/L NH₃·H₂O) and mobile phase B (40 mmol/L HNO₃, 80 mmol/L NH₃·H₂O) were used as the mobile phase gradient elution (93%) . Five arsenic compounds can reach baseline separation under the conditions of RF power of 1 500 W and atomization gas flow of 0.97 L/min. The detection limits ranged from 0.114 to 0.331 μg/L, and the inorganic arsenic content in rice samples ranged from 0.063 to 0.232 mg/kg. The results of determination of arsenic compounds in rice flour reference materials were all within the uncertainty range indicated by the standard. The recoveries were 86.7%~106.7%, and the precision was 1.9%-12.5%. Compared with national standards, the results of determination of arsenate in rice were relatively close (using this method, LC-AFS, LC-ICP-MS to detect the content of arsenate in rice samples 1 was 0.231, 0.226, 0.236 mg/kg, respectively). However, due to insufficient sensitivity, the national standard method is difficult to detect low levels of arsenic compounds (Arsenobetaine was not detected in rice sample 1). The method can detect the content of arsenobetaine in rice sample 1 was 0.023 mg/kg. Conclusion The established method can meet the requirements of inorganic arsenic determination in rice, and it is more rapid and accurate than the current national standard. It can better monitor and evaluate the content of i-As in rice, and provide accurate data for comprehensively grasping and evaluating the safety of rice consumption of residents.