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.

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.

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.

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 explore the perioperative risk factors in young children with obstructive sleep apnea.METHODS The 86 young OSA children admitted to Kunming Children's Hospital from January 2020 to December 2022 were divided into general ward group and ICU ward group according to their postoperative treatment.The clinical data of the two groups were compared and analyzed.RESULTS The course of disease and operation time of children in ICU ward group were significantly longer than those in general ward group,OAHI and ODI were significantly greater than those in general ward group,the intraoperative blood loss was significantly more than that in general ward group,MSaO2 and LSaO2 were significantly lower than those in general ward group,and the tonsil size and operation method composition ratio were significantly different from those in general ward group(P<0.05).There were no significant differences in sex composition ratio,age,weight,height,BMI and adenoid size grading ratio between the two groups(P>0.05).The OAHI values of the two groups were significantly negatively correlated with MSaO2 and LSaO2(r=-0.676,-0.724),and significantly positively correlated with tonsil size grade,ODI,operation time and intraoperative blood loss(r=0.242,0.967,0.321,0.446,P<0.05).There was no significant correlation with the course of disease(r=0.172,P>0.05).Multiple linear regression analysis showed that LSaO2 and ODI were independent risk factors for the severity of the child's condition.CONCLUSION The severity of the condition in young OSA children determines the perioperative risk and is influenced by the type of surgery.LSaO2 and ODI are independent risk factors which should be taken seriously by clinicians.

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 discuss the effect of Fuzheng Ruanjian Anticancer Formula on the malignant biological behaviors of the hepatocellular carcinoma HepG2 cells by requlating protein kinase B(Akt)/murine double minute 2(MDM2)/P53 signaling pathway.Methods:The HepG2 cells were treated with 0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1 Fuzheng Ruanjian Anticancer Formula for 48 h.CCK-8 method was used to detect the survival rates of the HepG2 cells in various groups,and the concentrations of Fuzheng Ruanjian Anticancer Formula for the subsequent experiments were screened.The HepG2 cells were divided into control group,low dose of Fuzheng Ruanjian Anticancer Formula group(0.2 g·mL-1),medium dose of Fuzheng Ruanjian Anticancer Formula group(0.4 g·mL-1),high dose of Fuzheng Ruanjian Anticancer Formula group(0.8 g·mL-1),SC79 group(8 mg·L-1 SC79),and high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group(0.8 g·mL-1 Fuzheng Ruijian Anticancer Formula+8 mg·L-1 SC79).CCK-8 method was used to detect the proliferation activities of the HepG2 cells in various groups;clone formation assay was used to detect the clone formation rates of the HepG2 cells in various groups;flow cytometry was used to detect the apoptotic rates of the HepG2 cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion HepG2 cells in various groups;Western blotting method was used to detect the expression levels of proliferating cell nuclear antigen(PCNA),cysteine aspartate specific proteinase(Caspase-3),matrix metalloproteinase(MMP)-2,MMP-9,phosphorylated Akt(p-Akt),phosphorylated MDM2(p-MDM2),and P53 proteins in the HepG2 cells in various groups.Results:As the increasing of concentrations of Fuzheng Ruanjian Anticancer Formula(0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1),the surival rates of the HepG2 cells were gradually decreased(P<0.05),and 0.2,0.4,and 0.8 g·mL-1 Fuzheng Ruanjian Anticancer Formula were selected for the subsequent experiments.The CCK-8 assay results showed that compared with control group,the proliferation activities of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05),in a dose-dependent manner,while the proliferation activity of the cells in SC79 group was significantly increased(P<0.05).Compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the proliferation activity of the HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The clone formation assay results showed that compared with control group,the clone formation rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the clone formation rate of the cells in SC79 group was significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the clone formation rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The flow cytometry results showed that compared with control group,the apoptotic rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruijian Anticancer Formula groups were significantly increased(P<0.05)in a dose-dependent manner,while the apoptotic rate of the cells in SC79 group was significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the apoptotic rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the numbers of migration and invasion cells in SC79 group were significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the numbers of migration and invasion HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the expression levels of Caspase-3 and P53 proteins were significantly increased(P<0.05)in a dose-dependent manner,while the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in SC79 group were significantly increased(P<0.05),and the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05),while the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05).Conclusion:Fuzheng Ruanjian Anticancer Formula may inhibit the proliferation,migration,and invasion of the HepG2 cells and promote the apoptosis,and its mechanism may be related to suppressing the Akt/MDM2 signaling pathway and upregulating the P53 proteim expression.

Objective:To advance the understanding of posterior reversible encephalopathy syndrome (PRES) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The medical history, diagnosis and treatment process, laboratory examination and imaging examination results of a patient who developed PRES after undergoing allo-HSCT at Changhai Hospital of Naval Medical University in November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 33-year-old woman, and she was admitted to the hospital with 17 years of diagnosis of aplastic anemia, 1 month after sibling-matched allo-HSCT, with low-grade fever for 1 week. On the 7th day of hospitalization, the patient experienced a sudden onset of seizures. After combining findings from cranial magnetic resonance imaging (MRI) and other relevant examinations, organic brain lesions were ruled out, and PRES was considered. The patient's condition improved after receiving antihypertensive, antiepileptic, anti-infection, and other appropriate treatments. A follow-up cranial enhanced MRI was performed 3 months after the onset of symptoms revealed the disappearance of lesions.Conclusions:PRES after allo-HSCT has the potential to yield favorable outcomes when it is promptly diagnosed and treated.

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.