The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

Colorectal cancer （CRC） ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years， there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence， and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway， the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies， and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes， such as proliferation， differentiation， and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine （TCM） can inhibit the proliferation， invasion， migration， and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore， this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy， thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years， research results have been updated rapidly， and previous literature summaries have failed to incorporate the latest findings， creating obstacles to accessing current literature. Therefore， this article supplements and summarizes information from the definition of the JAK/STAT pathway， association of this pathway with CRC， and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment. Methods: Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes. Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway. Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.

Objective To obtain the monitoring measurement range of quality indicators of red blood cells,plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province,explore the distribution of monitoring values and the change of monitoring level,so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei.Methods In 2023,the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected,scatter plots were made and the range markers were set,and the"mean±SD"line was taken as the upper limit and lower limit of the measurement range.In 2024,the monitoring values in 2023 were added,and the changes of two measurement ranges were compared to analyze the stability and overall level.Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin,washed erythrocyte-hemoglobin,washed erythrocyte-su-pernatant protein,cryoprecipitate coagulation factor-FⅧ,fresh frozen plasma-FⅧ,leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993,6.252 to 6.104,0.273 to 0.267,57.506 to 56.276,0.920 to 0.892,0.653 to 0.644 and 2.653 to 2.603,respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced disper-sion.Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells,hemoglobin content of the wash eryth-rocyte,protein content of supernatant of the wash erythrocyte,hemolysis rate of the wash erythrocyte,FⅧ content of the cryoprecipitate coagulation factor,plasma protein content of the fresh frozen plasma,FⅧ content of the fresh frozen plasma,platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476,44.915 to 44.861,0.280 to 0.283,0.137 to 0.142,133.989 to 133.271,60.262 to 60.208,1.301 to 1.277 and 3.036 to 3.033,respectively,and was closer to the national standard line,which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023.The long-term qualified rate of coagulation items was low,and no improvement has been ob-served.The stability of biochemical items has been enhanced but overall deviation has occurred,with the average value close to the national standard line.The possibility of subsequent testing failure has increased.The counting items showed no obvi-ous common characteristics.Conclusion The use of"mean±SD"in the analysis can visually display the distribution of mo-nitoring values of different items in Hebei,forming an indicator measurement range covering the past nine years.It shows the characteristics of each item,and provides reference for subsequent quality control laboratory data analysis of each blood sta-tions to takes active measures to improve the monitoring level.

Primary sclerosing cholangitis(PSC)is a cholestatic disease characterized by chronic progressive bile duct inflammation and has a low incidence rate and poor prognosis in China.There is still no drug therapy that can change the course of PSC,and liver transplantation is the only effective treatment for PSC,with a 5-year survival rate of 85%after transplantation.Drug therapy for PSC is facing great challenges based on the current status of PSC.At present,drugs for the treatment of PSC are in the stage of clinical trials and have shown certain application prospect,among which ursodeoxycholic acid is the most widely studied and commonly used drug.In addition,there are many emerging drugs in the pipeline.This article summarizes the latest advances in drug therapy for PSC.

Objective To investigate the relationship between the changes in vasopressin(VP)level and disease severity and prognosis in patients with septic shock(SS).Methods A total of 96 patients with SS in the hospital from December 2021 to December 2022 were selected as the study group,and 95 healthy volun-teers in the hospital during the same period were selected as the control group.The plasma VP levels of the two groups were compared,and their correlation with multiple organ dysfunction syndrome(MODS)score,a-cute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,serum C-reactive protein(CRP),and procalcitonin(PCT)levels were analyzed.The study group received shock treatment,and was divided into a good prognosis group and a poor prognosis group based on the prognosis after 28 days of hospitalization.The clinical data of the two groups were compared.Multivariate Logistic regression analysis was used to analyze the factors affecting poor prognosis.A new prediction scheme and a conventional prediction scheme were con-structed,and the predictive efficacy of different prediction schemes was evaluated using area under the curve(AUC),net reclassification index and comprehensive discrimination improvement index.Results Compared with the control group,the plasma VP level in the study group was significantly decreased,and MODS score,APACHE Ⅱ score,the levels of serum CRP and PCT were significantly increased,with statistical significance(P＜0.05).Pearson correlation analysis showed that plasma VP level was negatively correlated with MODS score,APACHE Ⅱ score,serum CRP and PCT level(r=-0.426,-0.519,-0.483,-0.395,P＜0.05).The proportion of diabetes mellitus,acute respiratory distress syndrome(ARDS),acute kidney injury(AKI),MODS score,APACHE Ⅱ score,serum CRP and PCT levels in the poor prognosis group were higher than those in the good prognosis group,while the plasma VP level was lower than that in the good prognosis group,with statistical significance(P＜0.05).Logistic regression analysis showed that concurrent ARDS,concurrent AKI,plasma VP,MODS score,APACHE Ⅱ score,serum CRP and PCT were all influential factors for poor prognosis of SS patients(P＜0.05).The AUC of plasma VP predicting poor prognosis of SS patients was 0.752,and the AUC of the new prediction scheme predicting poor prognosis of SS patients was greater than that of the conventional prediction scheme predicting poor prognosis of SS patients(P＜0.05).Conclu-sion Plasma VP level decrease in SS patients and closely relate to the severity of the condition.Based on the results of Logistic regression analysis,the new predictive model is established,which has certain predictive value for poor prognosis.

Objective To investigate the efficacy and safety of preemptive one lung ventilation(OLV)combined with disconnection technique for lung collapse during OLV with bronchial blocker(BB)in thoracoscopic surgery.Methods 75 patients who were scheduled for elective left lung segment or lobectomy under thoracoscopy were randomly divided into preemptive OLV group(group A),disconnection technique group(group B)and preemptive OLV combined with disconnection technique(group C),25 cases in each group.The time of complete lung collapse,surgeon satisfaction,pre-thoracic preparation time,OLV time,operation time,and occurrence of hypoxemia[percutaneous arterial oxygen saturation(SpO2)<90%]within 20 minutes after the onset of OLV were recorded;The lung collapse score(LCS)at the moment of pleural cavity opening(T0),1 min(T1),5 min(T2),10 min(T3)and 20 min(T4)after pleural cavity opening were recorded.Results Compared with group A and B,the complete lung collapse time in Group C was significantly shortened,and the surgeon satisfaction was significantly improved,the differences were statistically significant(P<0.05).There was no statistical significance in the complete lung collapse time and surgeon satisfaction between group A and B,the differences were not statistically significant(P>0.05).Compared with group A,the LCS at T0 in group B was lower than that in group A,but significantly higher at T1,the differences were statistically significant(P<0.05).The LCS at T1,T2,T3 and T4 in group C were significantly higher than those in group A and group B,the differences were statistically significant(P<0.05).The value of SpO2 at T2 in group C was obviously lower than that in group A and group B,the difference was statistically significant(P<0.05).Conclusion Preemptive OLV combined with disconnection technique can improve the lung collapse of the non-ventilated lung during OLV with BB in thoracoscopic surgery,shorten complete lung collapse time,with higher surgeon satisfaction,and higher LCS score during OLV.However,SpO2 during OLV still needs to be monitored.

OBJECTIVE: To explore the genotype-phenotype correlation of a Chinese pedigree affected with Lowe syndrome. METHODS: Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of his pedigree. RESULTS: The proband, a 3-year-and-5-month-old male, presented with multiple anomalies including congenital cataract, glaucoma, brain dysplasia, renal dysfunction and cognitive impairment. WES revealed that he has harbored a novel hemizygous missense variant of the OCRL gene, namely NM_000276.3: c.1255T>C (p.Trp419Arg) (GRCh37/hg19), which was derived from his unaffected mother. The same variant was not found in his elder brother who was healthy. The variant was predicted to be pathogenic according to ACMG/AMP guideline. Compared with previously reported cases of Lowe syndrome, our patient has displayed rare features including corpus callosum dysplasia, reduction of white matter, cerebral hypoplasia, laryngomalacia, sebaceous cyst, recurrent eczema, cryptorchidism, hypoglycemia and irritability. CONCLUSION Above finding has expanded the mutational spectrum of the OCRL gene, enriched clinical features of Lowe syndrome, and enabled genetic counseling for this pedigree.
Aged ; China ; Genetic Association Studies ; Humans ; Infant ; Male ; Mutation ; Oculocerebrorenal Syndrome ; Pedigree ; Phosphoric Monoester Hydrolases/genetics* ; Whole Exome Sequencing