OBJECTIVE To establish a ultra-high-performance liquid chromatography-mass spectrum/mass spectrum(UPLC-MS/MS) method for the determination of anlotinib in human plasma and assessment of clinical application. METHODS Zanubrutinib was used as internal standard and the extraction process was performed through protein precipitation method using acetonitrile, followed by separation on an Ultimate XB-C18(100 mm×2.1 mm, 3.0 μm) column using acetonitrile and 10 mmol·L−1 ammonium acetate-0.1% formic acid step-elution gradient. The flow rate was 0.6 mL·min−1 and injection volume was 5 μL. The mass analysis was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, and the mass spectrometer was set at m/z 408.1→339.1 for anlotinib and m/z 472.2→290.1 for internal standard, respectively. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability of the method and clinical application were investigated. RESULTS The method was validated over the concentration range of 1.0−100.0 ng·mL−1, with R2=0.998 4. The precision RSD was<9%, the recovery and matrix effect were 104.81%−107.32% and 102.54%−105.26%, respectively, and this method had good stability and was not affected by matrix effect. The method had been used for determined 52 advanced non-small cell lung cancer patients treated with anlotinib. The trough plasma concentration (Ctrough) was measured on day 43 after initiation of anlotinib treatment. Anlotinib Ctrough were higher than lower limit of quantitation (1.0 ng·mL−1) from 52 patients. The plasma concentration of anlotinib Ctrough was (11.38±4.29)ng·mL−1 with 37.66% coefficients of variation, which were shown large inter-patient variability. CONCLUSION This method is high sensitivity, specificity and accurate, and suitable for determination of anlotinib in human plasma.

Diffuse large B-cell lymphoma(DLBCL)in the oral gums is very rare and is prone to misdiagnosis and mistreatment.In this paper,2 cases of oral gingival DLBCL were reported.Their clinicopathological features,diagnosis,and differential diagnosis were discussed based on the literature of 21 cases of gingival DLBCL reported at home and abroad from 2008 to 2023.

Objective This article aims to investigate the association between hypertension and the risk of GSD by conducting a national multicenter study,a systematic review,and a meta-analysis.Methods The study was conducted in three stages.In the first stage,subjects were recruited for health examination in four hospitals in Chengdu,Tianjin,Beijing,and Chongqing,China,from 2015 to 2020,and the multivariate logistic regression analysis was used to investigate the association between hypertension and the risk of GSD in each center.In the second stage,Embase,PubMed,Wanfang Data,VIP,and CNKI databases were searched for related studies published up to May 2021,and a meta-analysis was conducted to further verify such association.In the third stage,the random effects model was used for pooled analysis of the results of the multicenter cross-sectional study and the findings of previous literature.Results A total of 633 948 participants were enrolled in the cross-sectional study,and the prevalence rate of GSD was 7.844%.The multivariate logistic regression analysis showed that hypertension was positively associated with the risk of GSD(P＜0.05).Subgroup analysis showed that there was no significant difference in the association between hypertension and GSD between individuals with different sexes,ages,and subtypes of GSD.A total of 80 articles were included in the systematic review and the meta-analysis,and the results showed that the risk of GSD was increased by 1.022 times for every 10 mmHg increase in diastolic pressure and 1.014 times for every 10 mmHg increase in systolic pressure.Conclusion Hypertension significantly increases the risk of GSD,and the findings of this study will provide a basis for the etiology of GSD and the identification of high-risk groups.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective: To analyze the semen quality parameters of sperm donor volunteers, so as to provide insights into male infertility control and related research. Methods: A total of 155 sperm donors were recruited from the Human Sperm Bank of Zhejiang Province using the convenience sampling method from January to March 2021. Demographic information were collected through questionnaire surveys. Semen were collected, and parameters including semen volume, sperm concentration, total number of sperm, forward motility rate and total sperm viability were measured. Semen quality was evaluated according to the WHO Laboratory Manual for the Examination and Processing of Human Semen. : Results Conclusion There were 20.65% of the 155 sperm donors with unqualified semen, and the unqualified rates of forward motility rate and total sperm viability were relatively high.

In this study, deep eutectic solvents (DESs) were used as excipients to prepare solid dispersion (SD) of scutellarin. The SD of scutellarin were prepared by melting method with cumulative dissolution rate as the index of investigation. The preparation conditions of SD of scutellarin were optimized by single factor experiment, which investigated the type of the carrier material, the type of DESs, and the ratio of the drug to the carrier. The optimum preparation conditions of DESs-SD were as follows: using Poloxamer 407 as the carrier material, PEG 200/urea (2∶1) as the DESs system, and the ratio of carrier, DESs, and drug was 6∶1∶1. The drug loading capacity of scutellarin in SD was 12.53% under the optimum preparation conditions. Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscope exhibited that scutellarin was amorphous form in the SD system. Furthermore, the stability of the DESs-based SD of scutellarin was evaluated by high temperature, high humidity, and strong light tests, which showed that the cumulative dissolution rate and scutellarin content of SD decreased with time under these conditions. Finally, the result of pharmacokinetic studies indicated that the oral absorption of the scutellarin could be increased using DESs as an excipient in the preparation of SD. The animal experiment was approved by the Experimental Animal Ethics Committee of Fujian University of Traditional Chinese Medicine (approval number: FJTCMIACUC 2023048). Consequently, this research offers a novel and effective approach for using DESs to enhance the oral bioavailability of active substances with low water solubility.

Objective To analyze the genetic etiology of a fetus with growth restriction,short long bones,small head circumference and enhanced kidney echoes,and explore the clinical significance of nonsense mutations in the NIPBL gene.Methods The clinical data of the fetus and his/her parents were collected.The variation sites of the NIPBL gene were verified by the chromosome karyotype a-nalysis of amniotic fluid,copy number variation detection in the human genome(CNV-seq),whole exome sequencing(WES)and Sanger sequencing.The databases such as China National Knowledge Infrastructure(CNKI),Wanfang Data,Wanfang Medical,and Pubmed were searched to further analyze the relationship between clinical symptoms and gene mutation sites in the fetus.Results The sequencing results showed that there was c.4555A>T heterozygous mutation in exon 21 of the NIPBL gene in the fetus,and that the same mutation was not detected in his/her parents.The above variation had not been included in databases such as Human Exon Data-base(ExAC),1000 genomes(1000G)and Genome Aggregation Database(gnomAD),and were comprehensively judged as harmful variation.Conclusion The detection of the nonsense variation,c.4555A>T(p.Lys1519?),in the NIPBL gene may provide experi-mental evidence for the prenatal diagnosis and fertility in this family.

Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Objective:To analyze the epidemiological and etiological characteristics of a death case of meningococcal meningitis in Hengyang city, Hunan Province in 2024.Methods:Epidemiological investigation of the death case was performed, and samples from the patient and close contacts were collected. Following cultivation and isolation, Neisseria meningitidis ( Nm) strains were analyzed by antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE), and whole-genome sequencing for analyzing epidemiological and etiological characteristics. Phylogenetic analysis was carried out using core genomic multilocus sequence typing (cgMLST). Results:The case was a 16-year-old high school boarding student with fulminant meningococcal meningitis. He had shock symptoms, and died within 24 h of the onset of symptoms. Six Nm strains were isolated from the patient and his roommates, belonging to two distinct clades. Isolate 144569 from the patient was highly homologous to isolate 144572 from a close contact, both belonging to the highly pathogenic sublineage L44.1 of CC4821. The typical molecular features was C: P1.7-2, 14: F5-101: ST4821 (CC4821). The two strains carried the antimicrobial resistance genes of gyrA-71 and penA-552, indicating reduced susceptibility to quinolone and penicillin, which was with their resistance phenotype. The isolates from four close contacts clustered within the same clade, characterized by the molecular features of B: P1.18-25, 9-18: ST5829 (UA). Conclusions:The death case is caused by Nm serogroup C from highly pathogenic sublineage L44.1 of CC4821. The spread of this isolate has the potential risk of outbreaks of invasive meningococcal disease. It is necessary to enhanced the molecular epidemiological surveillance, particularly focusing on the transmission of multiple serogroups of Nm among adolescents and the increasing exposure risk.

Objective:This study aims to explore how technological innovation can promote high-quality development of hospital discipline construction.Methods:The study elucidated the connotation, significance, and current status of high-quality development in discipline construction. Taking the Orthopedic Department of a tertiary hospital in Beijing as an example, it analyzed the problems and deficiencies in hospital discipline construction in China. Additionally, specific suggestions were put forward on how technological innovation can facilitate high-quality development of hospital discipline construction in China.Results:Strengthening technological innovation capacity, actively exploring collaborative technological innovation, optimizing research platform construction, enhancing talent cultivation and recruitment, and strengthening awareness of translating clinical research findings into practice were important approaches to achieving high-quality development of hospital discipline construction. These measures provided solid support for the high-quality development of hospitals.Conclusions:By enhancing the vitality of technological innovation and promoting the integration and coordinated development of disciplinary construction and technological innovation, it can assist in the high-quality development of medical disciplines in our country. Furthermore, it can accelerate the advancement of high-level first-class disciplinary construction, serving as an inexhaustible driving force for the cohesive high-quality development of Chinese hospitals.