ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Blood biochemical indicators are an important basis for the diagnosis and treatment by doctors. The performance of related instruments, the qualification of operators, the storage method and time of blood samples and other factors will affect the accuracy of test results. However, it is difficult to meet the clinical needs of rapid detection and early screening of diseases with currently available methods. Point-of-care testing (POCT) is a new diagnostic technology with the characteristics of instant, portability, accuracy and efficiency. Microfluidic chips can provide an ideal experimental reaction platform for POCT. This paper summarizes the existing detection methods for common biochemical indicators such as blood glucose, lactic acid, uric acid, dopamine and cholesterol, and focuses on the application status of POCT based on microfluidic technology in blood biochemistry. It also summarizes the advantages and challenges of existing methods and prospects for development. The purpose of this paper is to provide relevant basis for breaking through the technical barriers of microfluidic and POCT product development in China.
Humans ; Point-of-Care Testing ; Lactic Acid/blood* ; Microfluidic Analytical Techniques/methods* ; Blood Glucose/analysis* ; Point-of-Care Systems ; Blood Chemical Analysis/instrumentation* ; Uric Acid/blood* ; Cholesterol/blood* ; Dopamine/blood* ; Microfluidics/methods*

Objective:To analyze the causal relationship between lifestyle-based factors and the occurrence and development of hepatobiliary malignancies by Mendelian randomization study method,and to provide the potential clinical evidence for the prevention and treatment of hepatobiliary malignancies.Methods:The data from large-scale,independent genome-wide association studies(GWAS)were selected,and seven-step inclusion criteria for the instrumental variable screening were set up.The exposure lifestyles included the percentage of carbohydrate intake,percentage of fat intake,percentage of protein intake in the diet,coffee intake,weekly alcohol consumption times,leisure electronic screen exposure time,moderate to vigorous intensity physical activity(MVPA)during leisure time,sedentary behavior at work,age at first smoking,daily smoking quantity,current smoking status,and past smoking status,totaling 12 phenotypes.The primary analysis method used was the random effect model of the inverse variance weighted(IVW)method,and the heterogeneity was detected by Cochrane's Q test and the horizontal pleiotropy was detected by MR-Egger intercept method.Results:The current smoking status was significantly positively correlated with the increasing risk of extrahepatic cholangiocarcinoma(OR=1.607,95%CI:1.113-2.322,P=0.011).Higher coffee intake was causally linked to a higher risk of liver cancer and intrahepatic cholangiocarcinoma(OR=1.000,95%CI:0.999-1.000,P=0.012).In the physical activity,more MVPA was associated with the lower risk of liver cancer and intrahepatic cholangiocarcinoma(OR=0.998,95%CI:0.996-0.999,P=0.002).The Cochrane's Q test results showed that there was mild heterogeneity between MVPA and extrahepatic cholangiocarcinoma(Q=18.354,P=0.049)as well as the percentage of protein intake and intraphepatic cholangiocarainoma(Q=12.715,P=0.026),and the MR-Egger intercept method results showed there was no horizontal pleiotropy.Conclusion:There is a causal relationship between current smoking status and extrahepatic cholangiocarcinoma,and there is a causal relationship between more MVPA and the lower risk of liver cancer and intrahepatic cholangiocarcinoma.Education on smoking and physical activity for the patients may offer potential benefits for the prevention of hepatobiliary malignancies.

Objective:To study the clinical and genetic features of neonatal Schaaf-Yang Syndrome (SYS).Methods:The clinical data of a newborn with SYS admitted to our hospital in October 2022 were retrospectively analyzed. Using "Schaaf-Yang syndrome", "newborn", "preterm", "neonate" as keywords, we searched the CNKI, Wanfang Database, VIP database, Chinese Medical Journal Full Text Database, PubMed, Embase, Web of Science and the Cochrane Library for literature published during the date of establishment to March 24th, 2023. The clinical and genetic features of neonatal SYS from published literature were summarized.Results:The patient in this case was a female preterm infant with a gestational age of 33 +3 weeks, characterized by epiglottic collapse, hypotonia, poor response, weak sucking and swallowing, respiratory failure, and abnormalities such as bilateral low ear position and short limbs. The patient received symptomatic treatment, often failed to withdraw the ventilator, and had difficulty intubating. Meanwhile, whole exome sequencing identified a de novo truncated variant c.2892del (p.Trp965Glyfs*3) in the MAGEL2 gene of the patient. At 30 d after birth, the patient died after giving up treatment by her family. A total of 11 retrieved literatures had neonatal records, including 17 cases. The clinical features involved joint contracture (15/17), hypotonia (14/17), respiratory failure (12/17), and feeding difficulties (12/17). Most of the gene variation was truncated mutation, and only 1 heterozygote deletion mutation was found. These gene variation included c.1996dupC(p.Gln-666Profs*47) variation in 7 cases, c.1912C>T(p.Q638X) variation in 3 cases, c.1996C>T(p.Q666*) in 1 case, c.2847-2883del37 in 1 case, c.2118delT(p.Leu708Trpfs*7) in 1 case, c.1850G>A(p.RP617*) in 1 case, c.2167delG (p.Ala723Profs*4) in 1 case, c.2005C>T(p.Gln669) in 1 case, c.2892del(p.Trp965Glyfs*3) in 1 case, respectively. Conclusions:The main manifestations of neonatal SYS included hypotonia, feeding difficulties, respiratory failure and joint contracture. Most of the mutations were truncated mutations of c.1996dupC (p.Gln-666Profs*47).

OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity. RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.

OBJECTIVE To solve the problem of insolubility of itraconazole, improve its dissolution in vitro, and provide a reference for further industrial scale-up of the itraconazole multiparticle system. METHODS Itraconazole multiparticle system pellets were dissolved in an organic solvent and prepared in a fluidized bed by bottom spraying. Itraconazole and hydroxypropyl methylcellulose were sprayed onto the surface of the sucrose pellet core to form a uniform solid dispersion. The preparation parameters of the fluidized bed bottom spray coating were investigated by single factor method. The mass ratio of drug to carrier and core weight gain of the itraconazole multiparticle system were optimized by central composite design and response surface methodology with accumulative dissolution rate, application efficiency and adhesion rate as response values. Samples were prepared to verify the optimized prescription, the microscopic hierarchical structure of the itraconazole multiparticle system was observed by scanning electron microscope, and the solid dispersion in the itraconazole multiparticle system pellets was characterized by differential scanning calorimetry(DSC) and X-ray diffraction(XRD). The dissolution curves of itraconazole pellets and the physical mixture in 0.1 mol·L−1 HCl dissolution medium were compared to verify the solubilization effect. RESULTS Single factor method was used to determine the bottom spray coating parameters of the fluidized bed. The pumping speed was set as 3.0−5.0 mL·min−1, the atomization pressure was set as 1.5 bar, the inlet air volume was set as 110 m3·h−1, and the material temperature was set as 35 ℃. According to the central composite design and response surface methodology, the mass ratio of drug to carrier of the optimized prescription was 1∶1.5 and the core weight of the pill was 75%, and the response values reached the expected value. The result of scanning electron microscopy showed that the diameter of the itraconazole multiparticle system pellet was about 910 µm, the diameter of the sucrose pellet core was about 570 µm, the thickness of the drug loading layer was about 110 µm, and the thickness of encapsulation layer was about 11 µm. The results of DSC and XRD showed that itraconazole formed a uniform solid dispersion in the itraconazole multiparticle system pellets, which was amorphous. In the dissolution medium of 0.1 mol·L−1 HCl, the accumulative dissolution rate of the multiparticle system after 90 min was about 10 times that of the physical mixture, which showed that the solubilization effect was remarkable. CONCLUSION The dissolution of itraconazole in vitro can be significantly improved by processing itraconazole into pellets with multiparticle system and forming solid dispersion.

Objective To investigate the effect of cysteine-rich acidic secretory protein-like protein 1(SPARCL1)on atherosclerosis(AS)plaque formation.Methods A case-control study design was used,394 patients with con-firmed AS were selected as the case group,and 394 healthy medical examiners matched for age and gender were se-lected as the control group.The expression level of serum SPARCL1 was determined by enzyme-linked immunosor-bent assay;immunohistochemistry was used to assess the expression level and localization of SPARCL1 protein in the AS plaque region,and the expression of SPARCL1 protein was also detected in the neutrophils and monocytes of peripheral blood of AS patients and normal controls;SPARCL1 overexpressing and the recombinant adenoviral vec-tors were constructed to inhibit SPARCL1 overexpression and expression,and the effects of SPARCL1 on cell mi-gration were observed in the cell scratch assay using mouse macrophage cells(J774A.1)as target cells.Results Serum SPARCL1 levels in the AS patient group were lower than those in the healthy group(P<0.05);high SPARCL1 expression was detected in AS plaques and was mainly expressed in the cytoplasm of foamy cells;SPARCL1 expression levels in peripheral blood neutrophils and monocytes were lower than those in normal controls in AS patients(P<0.05);recombinant SPARCL1 overexpression and inhibition of expression of adenovirus was successfully constructed;the cell migration rate was decreased in J774A.1 cells that inhibited SPARCL1 expression and increased in J774A.1 cells that overexpressed SPARCL1(P<0.05).Conclusion SPARCL1 is highly ex-pressed in foam cells at the site of AS lesions,which may result from compensatory recruitment of peripheral blood monocytes and neutrophils,and SPARCL1 may be involved as a protective factors for blood vessels in inhibiting the development of AS plaques.

Objective: To investigate the expression of secreted protein acidic and rich in cysteine⁃like 1 (SPARCL1) in atherosclerosis (AS) and the association between SPARCL1 gene rs7695558 and rs1049539 polymorphism with the susceptibility to AS. Methods : In this case⁃control study ,209 AS patients were selected as the case group , and 208 healthy matched in age and sex were selected as the control group. The expression level of serum SPARCL1 was measured by enzyme⁃linked immunosorbent assay (ELISA) . Linear and Logistic regression analysis were used to evaluate the correlation between SPARCL1 level and vascular risk factors , lifestyle and demographic variables. Expression of SPARCL1 in tissue specimens was assessed by immunohistochemistry. Single nucleotide polymorphisms (SNPs) were genotyped by high resolution melting method. Chi⁃square test was used to analyze the relationship between rs7695558 and rs1049539 polymorphism and susceptibility to AS. Results: The serum expression level of SPARCL1 in AS patients was lower than that in healthy controls (Z = - 2. 916 ,P = 0. 004) . The level of SPARCL1 was related to age (P = 0. 027) and diastolic blood pressure ( P = 0. 008) , but not to sex and other cardiovascular risk factors (P > 0. 05) . The expression level of SPARCL1 in atherosclerotic lesions of coronary artery tissue increased. There was no significant difference in gene distribution of rs7695558 and rs1049539 between the case group and the control group by chi⁃square test (P > 0. 05) . In the recessive genetic model of rs7695558 , there was a difference in the distribution of genes with and without A. Patients without A allele (GG) had a lower risk of AS than patients with A allele (AA + AG) . The OR value was 0. 417 ,95% CI :0. 184 ~ 0. 945 , which was significant at 10% confidence level ( P = 0. 034) . Conclusion Rs7695558 , a new susceptible site related to AS risk , located in the intron of human SPARCL1 gene is identified for the first time in Anhui population of China , suggesting that SPARCL1 may play an anti⁃AS role as a vascular protective factor.

Objective　To investigate the biological characteristics of the serine protease inhibitor 15 (RmS-15) protein of Rhipicephalus microplus, and to perform molecular cloning and prokaryotic expression. Methods RmS-15 gene was amplified and sequenced to construct a phylogenetic tree to understand its evolutionary relationships. Bioinformatic tools were used to analyze the physicochemical properties, signal peptide, secondary and tertiary structure of the RmS-15 protein. In addition, DNA star and ABCpred were used to predict potential B-lymphocyte antigenic epitopes of RmS-15 protein, and potential T-lymphocyte antigenic epitopes were predicted by SYF-PEITHI and IEDB. Finally, the RmS-15 recombinant protein of Rhipicephalus microplus was obtained using the E.coli prokaryotic expression system and purified. Results The RmS-15 gene with 1 212 bp was successfully amplified, encoding a protein comprising 403 amino acids. Phylogenetic tree results indicated high conservation of the RmS-15 protein among different tick amino acid sequences, with the closest phylogenetic relationships to the Rhipicephalus haemaphysaloides and the Rhipicephalus sanguineus. The results of physicochemical property analysis showed a 20-amino acid signal peptide at the N-terminus of the RmS-15 protein, with a relative molecular weight and theoretical isoelectric point of 44 000 and 6.68, respectively. The protein showed an average hydrophilicity of 0.001, classifying it as a stably hydrophilic protein. The results of antigenicity analysis showed that the dominant fragments of B-cell antigenic epitopes of RmS-15 protein were 102-112 aa,147-152 aa and 207-215 aa, and the dominant fragments of T-cell antigenic epitopes were 3-11 aa, 6-14 aa, 27-33 aa, 34-37 aa. Protein expression results showed that RmS-15 protein exhibited high expression levels in the supernatant after induction with 0.8 mmol/L IPTG at 16 ℃ for 24 hours and reached a successful purification with a single band of the protein molecular weight of 44 000. Conclusions The method of prokaryotic expression and purification of RmS-15 protein from Rhipicephalus microplus was successfully established. Bioinformatics analysis demonstrated its strong antigenicity, suggesting its potential to develop as a candidate vaccine for ticks.