Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

Objective To analyze the composition patterns and indications of formulas containing the herbal pair of Bupleuri Radix and Scutellariae Radix(abbreviated as herbal pair Chaihu-Huangqin).Methods With Zhong Yi Fang Ji Da Ci Dian(Encyclopedia of Chinese Medicinal Formulas)as the data source,formulas containing herbal pair Chaihu-Huangqin were screened.Excel 2019,SPSS Modeler,and Cytoscape were employed to investigate the composition patterns and indications of the formulas containing the herbal pair.Results A total of 928 formulas containing the herb pair were identified,involving 293 herbs.Beyond Bupleuri Radix and Scutellariae Radix,high-frequency herbs of Glycyrrhizae Radix et Rhizoma,Ginseng Radix et Rhizoma,Angelicae Sinensis Radix,Paeoniae Radix Alba,Pinelliae Rhizoma,Gardeniae Fructus,and Poria are the primary ingredients of formulas containing herbal pair Chaihu-Huangqin.The herbs as the ingredient combinations were predominantly cold in nature and were bitter,pungent,or sweet in flavors,primarily acting on the liver and lung meridians.Association rule analysis revealed that herbal pair Chaihu-Huangqin was frequently use together with herbal groups of"Pinelliae Rhizoma-Ginseng Radix et Rhizoma-Glycyrrhizae Radix et Rhizoma"and"Poria-Ginseng Radix et Rhizoma-Glycyrrhizae Radix et Rhizoma".Formulas containing herbal pair Chaihu-Huangqin were indicated for 184 kinds of diseases,in particular for exogenous febrile diseases,heat syndrome,and ocular disorders.Complex network analysis and dosage analysis indicated that common combined herbs of Pinelliae Rhizoma,Ginseng Radix et Rhizoma,Gardeniae Fructus,and Puerariae Lobatae Radix were indicated for exogenous febrile diseases;common combined herbs of Paeoniae Radix Rubra,Coptidis Rhizoma,and Gardeniae Fructus were indicated for heat syndrome;and common combined herbs of Plantaginis Semen,Cimicifugae Rhizoma,and Cassiae Semen were indicated for ocular disorders.The dosage ratio of Bupleuri Radix-Scutellariae Radix consistently maintained a 1∶1 ratio across all above indications.Conclusion The herbal pair Chaihu-Huangqin functions to harmonize shaoyang meridian and demonstrates broad clinical applicability.The data mining study has revealed its dominant indications and combinatorial patterns,which will provide evidence-based insights for modern clinical practice.

Objective To explore the imaging features of primary cardiac tumors detected by echocardiography,CT and MR in children,and to analyze the value of each examination and the clinical examination strategies.Methods The clinical,pathological and imaging data of the children with primary cardiac tumors confirmed by surgery and pathology from Jun 2008 to Feb 2022 in Children's Hospital,Fudan University were analyzed retrospectively.Tumor size,location,motion,signal characteristics on different sequences,and pericardial involvement were evaluated on MR images.Results A total of 23 children(16 males and 7 females)were included.The age of onset ranged from 1 month to 13 years old,average on(54.45±58.57)months.While the onset age of rhabdomyomas was only(7.23±6.30)months.The clinical manifestations mainly included 6 cases of cardiac murmur,3 cases of cardiac insufficiency,3 cases of epilepsy,2 cases of cerebral infarction,and 1 case of arrhythmia.Pathological results showed that there were 22 cases of benign tumors(9 cases of fibromas,8 cases of myxomas,4 cases of rhabdomyomas and 1 case of lipoma)and 1 case of malignant tumor(rhabdomyosarcoma).Echocardiography has a high diagnostic accuracy for myxoma.CT showed a case of malignant rhabdomyosarcoma with invasion of the pericardium and compression of the pulmonary artery and bronchus.MR showed that the fibroma had significantly late gadolinium enhancement.The signal of rhabdomyoma was equal on T1WI,and slightly increased on T2WI,perfusion and late gadolinium enhancement sequences.Myxoma had high signal on T2WI and late gadolinium enhancement.It had obvious motions in Cine sequence.The signal of lipoma on each sequence was consistent with that of fat tissue,and there was no high signal of perfusion and late gadolinium enhancement.Conclusion All types of primary cardiac tumors in children have imaging characteristics.MR has great advantages in diagnosing cardiac tumors.The clinical team needs to select the appropriate examination method according to the actual medical situation.

Objective To investigate the distribution of Oncomelania hupensis snails in different water systems in Anqing City from 2016 to 2022, so as to provide insights into snail control in the city. Methods Snail survey data and distribution of water systems in snail-infested environments were collected from schistosomiasis-endemic areas of Anqing City from 2016 to 2022. The vector maps of towns and water systems in Anqing City were downloaded from National Geomatics Center of China. The GPS toolbox APP version 2.7.9 was downloaded from a smartphone to record the longitude and latitude of each snail-infested environment in Anqing City, which were loaded into the software LocaSpace Viewer version 4.4.6 to map the distribution of snail-infested environments. The area of snail habitats, area of emerging snail habitats, area of re-emerging snail habitats, type of snail habitats and density of living snails were descriptively analyzed. The spatial database of snail-infested environments in Anqing City was built with the software ArcGIS version 10.8, and the density of living snails was subjected to spatial autocorrelation analysis in snail-infested environments. The hotspot clusters of density of living snails were identified in snail-infested environments and the density of living snails was subjected to standard deviation ellipse analysis in snail-infested environments. Results A total of 515 snail-infested environments were identified in water systems in Anqing City in 2022. The area of snail habitats reduced from 6 909.32 hm² in 2016 to 6 087.48 hm² in 2022, with a reduction of 11.89%, and the areas of snail habitats reduced by 2.39%, 21.71% and 1.67% in the main stream of the Yangtze River, the Wanhe River system and the Caizihu River system in Anhui City, respectively, while the area of snail habitats increased by 3.94% in the Huayang River system. Emerging or re-emerging snail habitats were identified in Anqing City each year during the period from 2016 to 2018 and from 2020 to 2020. The density of living snails appeared a tendency towards a decline in the Wanhe River system (b = -0.030, t = -3.019, P < 0.05) and Huayang River system (b = -0.029, t = -4.296, P < 0.05) in Anqing City from 2016 to 2022, and fluctuated in the main stream of the Yangtze River (b = 0.028, t = 1.019, P > 0.05) and the Caizihu River system (b = 0.020, t = 1.877, P > 0.05). A positive global spatial autocorrelation was identified in the density of living snails in Anqing City each year from 2016 to 2022 (all Moran's I values > 0, all P values < 0.05), and the hotspot clusters of density of living snails in snail-infested environments were mainly distributed in the Wanhe River system (Shankou Township, Hongpu Township, Yueshan Township and Wanghe Townshpi), the main stream system of the Yangtze River (Dalongshan Township, Wanhe Farm, Haikou Township and Huayang Township), the Huayang River system (Dashi Township and Xuqiao Township) and the Caizihu River system (Xiushan Township and Fangang Township). The ratio of the long to short axes of the standard deviation ellipse was 1.72 to 2.06 for the density of living snails in snail-infested environments in Anqing City from 2016 to 2022, and snails were mainly distributed in the southwest to northeast, and appeared the east-west and north-south spread. Conclusions The areas of snail habitats and the density of living snails appeared a tendency towards a decline in different water systems in Anqing City from 2016 to 2022; however, there is still a risk of snail spread. Reinforced surveillance and precision control of snails are required in Anqing City.

The UV cross-linking immunoprecipitation (CLIP) technique was first established in 2003. Sequences of target RNAs and binding sites of specific RNA-binding proteins (RBPs) were identified within the entire transcriptome by UV cross-linking, immunoprecipitation, reverse transcription, and subsequent high-throughput sequencing. Over the last 20 years, CLIP has been continuously modified and improved. Advanced operability and accuracy have extended its application category. Currently, the widely used CLIP technologies include high-throughput sequencing with crosslinking-immunoprecipitation (HITS-CLIP), photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP), individual nucleotide resolution CLIP (iCLIP), enhanced CLIP (eCLIP), infrared-CLIP (irCLIP), etc. HITS-CLIP combines high-throughput sequencing with UV cross-linking immunoprecipitation. The 254 nm UV cross-linking and RNAase digestion steps allow the technology to capture transient intracellular RBP-RNA interactions. However, there are limitations in the efficiency of UV cross-linking, with low resolution and high intrinsic background noise. For PAR-CLIP, photoactivatable ribonucleoside was incorporated into RNA molecules, and RBP cross-linked with RNA by 365 nm UV light to improve cross-linking efficiency and resolution. Cross-linking mediated single-base mutations provide more accurate binding site information and reduce interference from background sequences. Long-term alternative nucleotide incorporation, on the other hand, can be cytotoxic and may skew experimental results. iCLIP can identify RBP-RNA cross-linking sites at the single nucleotide level through cDNA circularization and subsequent re-linearization steps, but it has more experimental procedures, and partial cDNAs lost in the circularization step are inevitable. eCLIP discards the radioisotope labeling procedure and reduces RNA loss by ligating adaptors in two separate steps, greatly improving the library-building efficiency, and reducing bias associated with PCR amplification; however, the efficiency of immunoprecipitation cannot be visually assessed at the early stage of the experiment. The irCLIP technique replaces radioisotopes with infrared dyes and greatly reduces the initial number of cells required for the experiment; however, an infrared imaging scanner is essential for the irCLIP application. To address more particular scientific issues, derivative CLIP-related techniques such as PAPERCLIP, cTag-PAPERCLIP, hiCLIP, and tiCLIP have also been developed in recent years. In practice, the aforementioned CLIP approaches have their advantages and disadvantages. When deciding on a technical strategy, we should take into account our experimental objectives and conditions, such as whether we need to precisely define the RNA site for binding to RBP; whether we have the necessary experimental conditions for working with radioisotopes or performing infrared imaging; the amount of initial sample size, and so on. In addition, the CLIP technique has a relatively large number of procedures and can be divided into several successive experimental modules. We can try to combine modules from different mainstream CLIP technologies to meet our experimental requirements, which also gives us more opportunities to improve and refine them and to build more targeted derivative CLIP technologies according to our research objectives.

Objective:To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor(G-CSF)or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT),and to analyze the length of hospital stay,hospitalization cost and post-transplant survival of the patients.Methods:A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022,the febrile neutropenia,the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed.The length of hospital stay,total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared.Results:A total of 102 cases were included in this study,including 57 cases of multiple myeloma,36 cases of acute leukaemia,7 cases of lymphoma,3 cases of myelodysplastic syndrome,1 case of light chain amyloidosis,and 1 case of POEMS syndrome.47 patients received levofloxacin+G-CSF antibacterial prophylaxis,and 55 patients received G-CSF supportive therapy.In the levofloxacin+G-CSF group,40 cases(85.11％)developed febrile neutropenia,and 13 cases(27.66％)were confirmed as bacterial infection.In the G-CSF group,44 cases(80.00％)developed febrile neutropenia,and 16 cases(29.09％)were bacterial infection.There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups(x2=0.46,P=0.50;x2=0.03,P=0.87).The use rate of intravenous antibiotics in the levofloxacin+G-CSF group was 85.11％(40/47),which was not statistically different from 85.45％(47/55)in the G-CSF group(X2=0.04,P=0.84).The detection rates of levofloxacin-resistant bacteria in the levofloxacin+G-CSF group and G-CSF group were 8.57％(3/35)and 21.43％(6/28),respectively,with no statistical difference(x2=0.65,P＞0.05).The median length and median cost of hospitalization in the levofloxacin+G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan,with no statistically significant differences(t=3.00,P=0.09;t=0.94,P=0.09).Within 90 days after transplantation,two cases(4.26％)died in the levofloxacin+G-CSF group and one case(1.82％)died in the G-CSF group,with no statistically significant difference between the two groups(x2=0.53,P=0.47).Conclusion:Application of levofloxacin+G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.

Objective:To evaluate the clinical characteristics and risk factors of infections occurring during hospitalization in patients with multiple myeloma (MM) treated with new generation therapies (including immuno-modulatory drugs,proteasome inhibitors and monoclonal antibodies).Methods:The clinical data were collected from 155 patients with multiple myeloma who were treated in Shanxi Bethune Hospital from March,2017 to March,2022 and were retrospectively analyzed.For this study,the following therapies were considered to be new generation therapies:lenalidomide,pomadomide,bortezomib,ixazomib,daratumumab. The clinical characteristics and risk factors of infection were analyzed.Results:A total of 155 patients were included in this study.The median follow-up time was 20 months.Of 155 patients with MM,242 infection episodes were identified.Among the 242 infections,the incidence of clinically defined infection (CDI)was the highest (186,76.86％),followed by microbiologically defined infection (MDI)in 50 cases (20.66％),and fever at unknown focus (FUF)in 6 cases (2.48％).35 cases (14.46％)of bacteria,10 cases (4.13％)of viruses,and 5 cases (2. 07％)of fungi were clearly infected.The most common site of infection was the lower respiratory tract in 90 cases (37.19％),the upper respiratory tract in 83 cases (34.30％),and the digestive tract in 27 cases (11.16％).All-cause mortality was 8.39％(13/155).In univariate analysis,there was a higher correlation between ISS stage Ⅲ,the number of treatment lines ≥2,frail and infected patients with multiple myeloma.In multivariate analysis,ISS stage Ⅲ(OR=2.96,95％CI:1.19-7.40,P=0.02),the number of treatment lines ≥2 (OR=2.91,95％CI:1.13-7.51,P=0.03)and frail (OR=3.58,95％CI:1.44-8.89,P=0. 01)were risk factors for infection in patients with multiple myeloma in the era of new drugs.Conclusion:Patients with multiple myeloma treated with new agents are prone to bacterial infection during hospitalization.ISS stage Ⅲ,lines of therapy(≥2)and frail were associated with high risk for infection.

As a long-standing research focus in electroanalytic chemistry,electrochemical biosensors have attracted immense interest in detection of biological targets such as small molecules,proteins,enzymes,nucleic acids,exosomes,circulating tumor cells (CTCs),bacteria,and viruses. etc. The highly sensitive and selective electrochemical detection of biological targets relies on the use of the specific biorecognition elements (BREs) and efficient signal amplification strategies. In this review,the typically used BREs and amplification strategies in electrochemical biosensing were summarized. On the basis of the interactions between BREs and targets,the enzyme/substrate-based and receptor/ligand-based electrochemical biosensors were first introduced,focusing on the BREs used in the electrochemical detection of nucleic acid targets and non-nucleic acid targets. Then,the representative use of various isothermal nucleic acid amplification technologies,catalytic reactions,functionalized nanocarriers,and polymer materials in amplified electrochemical detection of biological targets were introduced. The challenges with respect to the practical use of electrochemical biosensors and the prospect of electrochemical biosensing were discussed.

Objective: To analyze the epidemiological characteristics and genetic characteristics of sapovirus (SaV) in a cluster of schools in Changzhou, so as to provide a reference for the treatment of clustered vomiting and diarrhea events in schools. Methods: The epidemiological data and laboratory test data of sapovirus clusters in Changzhou from 2019 to 2022 were collected and analyzed. Partial VP1 genes of SaV positive samples were amplified and sequenced for phylogenetic analysis. Results: A total of 8 cases of clusters of SaV epidemics were reported in Changzhou City from 2019 to 2022, with 118 reported cases. The total attack rate was 1.47%, and the median of the attack number was 15. There were 6 outbreaks in kindergartens and 2 outbreaks in primary schools, which were reported in the epidemic period from September to December. The main clinical manifestations were vomiting (113 cases, 95.76 %), abdominal pain (39 cases, 33.05%), and diarrhea (16 cases, 13.56%). Among the 8 outbreaks, 17 sample strains were successfully sequenced. 5 outbreaks were GII.3 , and the other 3 outbreaks were GI.1, GI .3 and GII.2. GI and GII were the main genotypes in this area, and GII .3 was the predominant strain. Conclusion SaV is an important pathogen in the clusters of vomiting and diarrhea in schools after the transmission of norovirus. Continuous surveillance of SaV should be carried out to further understand its epidemiological characteristics and genotype distribution, so as to provide scientific basis for the prevention and control of the epidemic in schools.