Objective: To prepare platelet membrane biomimetic liposomes loaded with vincristine sulfate (VCR) for targeted delivery to tumor. Methods: Vincristine sulfate liposomes (LIPO) were prepared using the pH-gradient method, followed by the fusion of platelet membranes and subsequent drug loading to obtain platelet membrane biomimetic liposomes (PLM-LIPO). The particle size, polydispersity index (PDI), Zeta potential, and drug encapsulation efficiency (EE%) of both liposomes were characterized. The tumor-targeting capability was evaluated through in vitro cellular experiments and in vivo biodistribution studies. Results: The optimal preparation conditions for LIPO were determined as follows: DPPC-to-cholesterol molar ratio of 1∶1, internal aqueous phase of 0.3 M pH 4.0 citrate buffer, external aqueous phase of 1 M Na HPO solution, drug-to-lipid ratio of 1∶10, drug loading temperature of 60℃, and loading time of 10 minutes. The LIPO exhibited a mean particle size of (147.3±2.24) nm, PDI of 0.078±0.014, Zeta potential of (-3.54±0.75) mV, and EE% of 91.37±0.47. For PLM-LIPO, prepared via membrane fusion followed by drug loading, the mean particle size was (185.3±3.61) nm, PDI was 0.075±0.022, Zeta potential was (-18.91±1.54) mV, and EE% was 63.36±2.45. In the CD62P validation experiment, the fluorescence intensity of PLM-LIPO was five times higher than that of LIPO. In vitro cellular uptake experiments revealed that PLM-LIPO showed 1.3-fold and 1.2-fold higher uptake rates compared to LIPO at 6 h and 12 h, respectively. In vivo experiments demonstrated that 1h after administration, the accumulation of PLM-LIPO at tumor sites was 4-fold higher than that of LIPO and 6-7 times higher than that in healthy mice. Conclusion: The platelet membrane biomimetic liposomes loaded with vincristine sulfate were successfully developed. Both cellular uptake and tissue distribution studies confirmed the PLM-LIPO enhanced tumor-targeting capability.

OBJECTIVES: Managing patients with refractory head and neck cancer pain is one of the more challenging issues in clinical practice, and traditional intrathecal drug delivery also fails to provide adequate analgesia. There are currently no comprehensive and effective treatment methods. This study aims to observe the efficacy and safety of treating intractable head and neck cancer pain with morphine pump via lumbar approach to the prepontine cistern. METHODS: A total of 18 patients with intractable head and neck cancer pain treated with prepontine cistern morphine pumps were selected from the Department of Pain Management, Second Xiangya Hospital, Central South University between September 2019 and July 2023. Statistical analysis was performed on patients' preoperative and postoperative (1 week, 1 month, and 2 months after surgery), Numerical Rating Scale (NRS) scores, Self-Rating Depression Scale (SDS) scores, daily oral morphine consumption, the number of daily breakthrough pain episodes, and postoperative daily intrathecal morphine dosage. RESULTS: The NRS scores, SDS scores, daily oral morphine consumption, and the number of daily breakthrough pain episodes of patients at each time point after surgery were significantly lower than before surgery (all P<0.05). With the gradual increase in the dosage of intrathecal morphine, the daily oral morphine consumption of patients at each postoperative time point was significantly reduced compared to preoperative levels (all P<0.05). The complications related to the operation were mild, including nausea in 5 cases (31.3%), headache in 2 cases (12.5%); hypotension, urine retention, hypersomnia and constipation in 1 case (6.3% each), and no serious adverse events occurred. All improved and were discharged after symptomatic treatment. CONCLUSIONS The implantation of prepontine cistern morphine pump effectively controls intractable head and neck cancer pain, demonstrating characteristics of minimal invasiveness, mild side effects, and low medication dosage under the premise of standardized procedures.
Humans ; Morphine/administration & dosage* ; Male ; Female ; Middle Aged ; Head and Neck Neoplasms/surgery* ; Analgesics, Opioid/administration & dosage* ; Cancer Pain/drug therapy* ; Pain, Intractable/etiology* ; Aged ; Adult ; Infusion Pumps, Implantable ; Pain Management/methods*

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objective To observe changes of CT quantitative indexes in patients with untreated chronic obstructive pulmonary disease(COPD)and relationships with pulmonary function indicators.Methods Totally 99 patients with untreated COPD were retrospectively enrolled.According to the degrees of airflow obstruction,the patients were divided into group A(GOLD grade 1 with mild obstruction,n=36),group B(GOLD 2 with moderate obstruction,n=37)and group C(GOLD 3 or 4 with obvious obstruction,n=26).The results of chest CT and pulmonary function tests conducted at the first diagnosis and the follow-up,as well as their correlations were analyzed.CT quantitative indicators included the whole lung volume,low-attenuation areas less than-950 percentage(LAA％),total number of vessels per 1 cm2 of lung surface area(Ntotal/LSA),total number of vessels with area less than 5 mm2 per 1 cm2 of lung surface area(N＜5mm2/LSA),the square root of the wall area of a hypothetical airway with a 10 mm internal perimeter(Pi10),the entire volume,wall thickness and wall area percentage(WA％)of airway wall,etc.,while results of pulmonary function tests included the forced expiratory volume in one second(FEV1)after administration of a bronchodilator,forced vital capacity(FVC),the ratio FEV1/FVC and FEV1 expressed as percent predicted(FEV1％).Results Compared with those at the first diagnosis,the follow-up results of FVC,FEV1,FEV1/FVC,Ntotal/LSA and N＜5mm2/LSA were lower,whereas LAA％,Pi10 and entire volume of airway were all higher in each group(all P＜0.05).Compared with those in group A,group B and C had decreased LAA％and increased Pi10,and the magnitude increased with the severity of airflow obstruction(all P＜0.05).LAA％,Pi1o and entire volume of airway wall were negatively correlated with pulmonary function indicators(all P＜0.05),while Ntotal/LSA and N＜5 mm2/LSA were positively correlated with pulmonary function indicators(all P＜0.05).Conclusion CT quantitative parameters,including LAA％,Ntotal/LSA,N＜5mm2/LSA,Pi10 and entire volume of airway wall were related to pulmonary function,which might reflect the longitudinal changes of airways and blood vessels in COPD patients.

Objective To observe the effects of different virulence types of Helicobacter pylori on pepsin and inflammatory factors.Methods 110 patients admitted from December 2021 to March 2023 were collected and divided into HP positive group(n=79)and HP negative group(n=31)according to 13 carbon breath test results.The HP positive group was divided into type Ⅰ group(n=52),type Ⅱ group(n=11)and undetermined group(n=16)according to the Helicobacter pylori antibody typing.The HP negative group was selected and divided into blank control group(n=12).Gastric juice pH value,sodion(Na+),potassium(K+),chloridion(Cl-),IL-6,IL-8,gastrin 17(G-17),pepsinogen Ⅰ(PG Ⅰ)and pepsinogen Ⅱ(PG Ⅱ)were detected in all patients.Results Th-ere was no difference in pH,Na+,Cl-,K+ between Hp positive group and Hp negative group(P>0.05).The content of Cl-in HP-positive group was lower than that in HP-negative group(P<0.05).The levels of IL-6,IL-8,G-17,PG Ⅰ and PG Ⅱ in HP-positive group were significantly higher than those in HP-negative group(P<0.05).There was no significant difference in pH,Na+ and K+ between type Ⅰ group and type Ⅱ group,undetermined group and blank control group(P>0.05).The content of Cl-in type Ⅰ group and undetermined group was lower than that in blank control group(P<0.05).The levels of IL-6,IL-8 and PG Ⅰ in type I group were higher than those in type Ⅱ group,undetermined group and blank control group(P<0.05).There was a significant difference in PG Ⅱ between the blank control group and the other groups(P<0.05).There was no difference in G-17 content between type Ⅰ group and undetermined group(P>0.05).The level of G-17 in type I group was higher than that in type Ⅱ group and blank control group(P<0.05).Conclusion Type I Hp infection may cause gastric mucosal injury by increasing the expression of IL-6,IL-8 and G-17,and then lead to abnormal digestive function.

【Objective】 To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. 【Methods】 LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. 【Results】 The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL^-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL^-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. 【Conclusion】 The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To investigate the status quo of psychological distress among parents of children with cancer and analyze its influencing factors.Methods:Totally 334 parents of pediatric oncology patients meeting the inclusion criteria were selected by convenience sampling from Hunan Children's Hospital between June and October 2022. A questionnaire survey was conducted using a general information questionnaire, Distress Thermometer, Social Support Rating Scale, and Mishel Uncertainty in Illness Scale-Family Member Form.Results:A total of 334 questionnaires were distributed, with 298 valid responses received, making the effective response rate 89.22%. The DT score of the 298 parents of pediatric oncology patients was (7.58±2.85). Multiple linear regression analysis revealed that parental gender, the impact of caregiving on income, economic pressure, uncertainty in illness, and social support were significant influencing factors of the parents' psychological distress ( P<0.05) . Conclusions:The psychological distress of parents of children with cancer is at a relatively high level and is influenced by multiple factors. Medical professionals can implement targeted interventions based on specific circumstances to alleviate the psychological distress of these parents.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To explore changes of acid-base metabolism in the brain tissue of patients with chronic ischemic cerebrovascular disease (CICVD) using MRI amide proton transfer-weighted (APTw) imaging.Methods:This was a cross-sectional study. From January 2021 to July 2022, thirty-nine patients with CICVD at West China Hospital, Sichuan University were retrospectively included. All patients received CT perfusion (CTP) and APTw imaging. NeuBrainCARE brain perfusion software was used to analyze the impaired perfusion sites and measure the mean transit time (MTT) and time to peak (TTP). Standard spatial matching between CTP and APTw images was performed to measure the APTw values of the same sites. For comparison with normal tissue, APTw values were measured for normal-appearing white matter (NAWM) in the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere in areas of impaired perfusion. ANOVA was used to compare the APTw values of impaired perfusion brain tissue, ipsilateral cerebral NAWM, contralateral cerebral NAWM, and ipsilateral cerebellar NAWM. The Bonferroni method was used to correct for multiple comparisons. Pearson correlation coefficient was used to analyze the correlation between APTw values and MTT and TTP in the cerebral tissue with impaired perfusion.Results:In 39 patients with CICVD, both the mean and minimum APTw values of cerebral tissue with impaired perfusion were significantly lower than those in the NAWM of the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere ( P<0.001). In the NAWM of the cerebellar hemispheres with unimpaired perfusion, both the mean and minimum APTw values were significantly higher than those in the ipsilateral cerebral hemispheres and the contralateral cerebral hemisphere ( P<0.001). Correlation analysis showed that MTT was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.90 and -0.82, P<0.001). TTP was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.86 and -0.78, P<0.001). Conclusion:APTw value can reflect acidosis in cerebral tissue with impaired perfusion in patients with CICVD.