OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues（MCACs） and investigate the activities of them against breast cancer. METHODS The analogues F1， F2， and F3 were obtained by aldol condensation reaction， and their antitumor activities（including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549） were detected by MTT assay [evaluated with half inhibitory concentration（IC50）]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1， F2 and F3 acting on breast cancer， and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high， medium and low concentrations （16， 8， 4 μmol/L） of F1， F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1， F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin， IC50 of analogues F1， F2 and F3 to A549 and MCF-7 cells（except for IC50 of analogue F2 to A549 cells） were decreased significantly（P＜ 0.05 or P＜0.01）； among them， IC50 of analogue F2 to MCF-7 cell was the lowest， being（9.67±1.27） μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1， F2 and F3 with the first core target epidermal growth factor receptor （EGFR）， protein kinase B （AKT） and AKT were 5.909 2， 8.402 5 and 6.486 6， respectively； high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells（P＜0.01）， while low， medium， and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells（P＜0.05 or P＜0.01）. Medium concentration of F1， F2， and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells（P＜0.01）. CONCLUSIONS Designed and synthesized MCACs F1， F2 and F3 all have good anti- breast cancer activity， and F2 has better anti-breast cancer activity.

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To explore the relationship between postoperative defecation dysfunction and quality of life in children with anorectal malformation(ARM)complicated with spinal cord anomalies(SCA)and analyze the impact of different types of SCA on ARM patients in order to provide a reference for the early clinical identification of high-risk children with poor prognosis.Methods A retrospective analysis was conducted on 282 ARM neonates admitted to our department between June 2015 and April 2021.Radiological examinations were applied to evaluate the development of the spinal cord,and Rintala score and the PedsQL 4.0 scale were employed to assess postoperative defecation function and quality of life,respectively.According to their SCA types and other complications,the patients were grouped.The relationship between these factors and defecation function as well as quality of life was then analyzed.Results Among the 282 subjected children,104(36.9%)had SCA.The incidence of SCA varied significantly across different types of ARM(P=0.002),with the highest incidence observed in vaginal fistula patients(100.0%)and the lowest in children without fistula(13.6%).Radiological findings revealed that sacral bone anomalies were common,with absent coccyx(62.7%)and vertebral anomalies(69.8%)being the most prevalent.The SCA group had significantly lower Rintala bowel function score(12.70±3.24)and PedsQL 4.0 quality of life score(81.42±5.03)than the non-SCA group(P<0.001).As the increment of SCA types,both the Rintala score and PedsQL 4.0 score were in a significant downward trend(P<0.001).Among the children with different types of SCA,those with tethered cord syndrome had the statistically lowest Rintala score(8.05±2.35,P<0.05).Meanwhile,their PedsQL 4.0 score(75.90±3.35)was significantly lower than those of other types except syrinx(P<0.05).Multiple linear regression analysis indicated that both SCA and sacral bone anomalies exerted notably negative impacts on the Rintala score and PedsQL 4.0 score(P≤0.001),with SCA having the most pronounced effect.Conclusion SCA is closely associated with postoperative defecation dysfunction and diminished quality of life in ARM children.The greater the type and number of SCAs,the worse the postoperative defecation function and quality of life.Early identification of concomitant SCAs holds significant clinical value for predicting postoperative outcomes in ARM patients.

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

This study aimed to address the limitations of current diagnostic methods for well leg compartment syndrome(WLCS),including invasiveness,high costs,and insufficient accuracy,by proposing a solution based on electrical impedance tomography(EIT)technology.The electrical response characteristics of the human calf muscle to changes in compartment pressure using EIT were investigated,aiming to visualize the effects of pressure variations on the electrical properties within the compartment and to provide technical support for early non-invasive detection of WLCS.EIT sensors were placed on the right calf of the experimental subjects,with pressure applied externally to the right thigh.Measurements were conducted in two phases:pre-pressure(pre)and post-pressure(post).Pre-pressure,the conductivity distribution image σpre was measured when the calf was placed horizontally.Post-pressure,the calf was raised at an angle of approximately 30°,and pressures of 0,40,80,and 120 mmHg were applied to the right thigh,and the corresponding conductivity distribution images σP=0,σP=40,σP=80,andσP=120were recorded.To quantitatively analyze the pressure effects on the compartment response,paired sample t-test was used to assess the spatial-mean conductivity((σ))from the EIT reconstructed images.Compared to the horizontal position of the right calf,raising the calf at approximately 30° resulted in a significant increase in the spatial-mean conductivity(σ)of the M1 compartment.Furthermore,when pressure was applied to the right thigh while the calf remained at a 30° angle,the spatial-mean conductivity of the M1 compartment σM1 showed an increasing trend with rising pressure.The results indicated that as compartment pressure increased,the volume of extracellular fluid and ion concentration significantly increased,leading to an increase in conductivity,which reflected ischemia and hypoxia in muscle tissue and the related pathophysiological changes.EIT,due to its high sensitivity to conductivity changes,offered a potential effective diagnostic method for non-invasively monitoring the onset and progression of muscle compartment syndrome.

The integrin alpha 2（ITGA2）gene locates on chromosome 5q11.2，encodes the α 2 subunit of the integrin family.The α 2 subunit is found on many cell surfaces.The α 2 subunit plays an important role in the regulation of platelet aggregation，cell migration，cell proliferation and angiogenesis.Through a wide range of studies conducted in recent years，researchers have discovered that this gene is linked to some diseases，such as rheumatoid arthritis，pediatric sickle cell disease，Kawasaki disease，malignant tumor and biliary atresia.These studies have contributed to the early identification of diseases associated with this gene and the exploration of diagnostic and therapeutic solutions for them.This article reviews the advancements in research concerning the association of ITGA2 gene with various diseases.

Immunotherapy had completely changed the treatment for patients with advanced non-small cell lung cancer.However,due to its low response rate as a monotherapy,many patients had not been able to benefit from the treatment.The combination of immunotherapy with anti-angiogenic drugs and chemotherapy might have helped to address this issue,and the regimen of atezolizumab with bevacizumab,carboplatin,and paclitaxel(ABCP)had been approved as a first-line treatment for advanced metastatic non-small cell lung cancer,holding great potential for application.This review had summarized the antitumor mechanisms of the ABCP regimen,had concluded the current status of its clinical application for different subgroups and treatment sequences,the safety and cost-effectiveness of the regimen,as well as the possibilities for alternative drug choices within the ABCP regimen and the development of new drugs,providing a reference for the personalized application of the ABCP regimen in patients with non-small cell lung cancer.

Objective To investigate the relationship between the development of terminal rectal ganglion and spinal cord/sacral abnormalities in boys with complex anorectal malformations(ARMs)in order to improve the understanding of rectal ganglion development abnormalities in ARMs patients.Methods A retrospective trial was conducted on the male patients with complex ARMs admitted to our hospital from 2015 to 2021.The terminal rectal specimens were taken from them during anoplasty.According to the findings on development of terminal rectal ganglion after HE staining,the patients were classified into G1 group(ganglion cells observed)and G2 group(no ganglion cells observed).Imaging techniques were used to evaluate whether there were abnormalities in the spinal cord and sacrum,and their correlation with the terminal rectal ganglion development was analyzed.Results A total of 139 patients were enrolled,and their median age at anoplasty was 5.77(4.57,6.97)months.There were no significant differences between the G1(n=80,57.6％)and G2(n=59,42.4％)groups in ARMs pathological type(P=0.706)and age at surgery(P=0.140).Radiological findings showed there were 48 cases(34.5％)of spinal cord anomalies(SCA),25 cases(18.0％)of sacral abnormalities and 18 cases(12.9％)of coccyx abnormalities.No significant differences were observed in the incidences of SCA and sacral abnormalities between the G1 and G2 groups(P＜0.05).Moreover,the differences of fatty filum terminale and syrinx were statistically significant(P＜0.05).In addition,the ratio of sacrum to coccyx between the G1 and G2 groups were 0.72±0.10 vs 0.67±0.12(P＜0.05)of the anteroposterior position and 0.77±0.09 vs 0.72±0.09(P＜0.05)of the lateral position.Multivariate logistic regression analysis showed that sacral abnormalities,fatty filum terminale and syrinx were independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.Conclusion The development of terminal rectal ganglia in male patients with ARMs is closely associated with the abnormalities of spinal cord and sacrum.Sacral abnormalities,fatty filum terminale and syrinx are independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.

Amantadine(AMD)residue can accumulate in organisms through the food chain and cause serious harm to human body.AMD can specifically bind to AMD specific aptamer and cause its conformation to change from a random single strand to a stem-loop structure.To avoid the influence of excess nucleotides on binding of aptamer to AMD,the truncation of the AMD original aptamer J was optimized by retaining an appropriate stem-loop structure,and a new type of truncation aptamers was developed in this work.By comparing the truncated aptamer with the original aptamer,it was found that the truncated aptamer J-7 had better affinity and specificity with AMD.The detection limit of AMD was 0.11 ng/mL by using J-7 as specific recognition element and molybdenum disulfide nanosheet(MoS2Ns)as signal amplification element.The developed method base on truncated aptamer J-7 was used for detection of AMD in milk,yogurt and SD rat serum samples for the first time with recoveries of 86.6%-108.2%.This study provided a reference for truncating other long sequence aptamers and provided a more sensitive detection method for monitoring AMD residues in food.