Objective To investigate the effects of endostatin combined with icotinib on chemotherapy sensitivity,tumor markers,and prognosis in patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 88 patients with advanced NSCLC admitted to our hospital from January 2019 to August 2020 were selected and randomly assigned to two groups,with 44 patients in each group.The patients in both groups were treated with pemetrexed+cisplatin(PP)chemotherapy,whereas those in the control group were administered echitinib and those in the observation group was treated with endostatin combined with icotinib.Patients in the two groups were assessed for clinical efficacy,tumor markers[carbohydrate antigen(CA)50,carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA)21-1],T lymphocyte subsets,microRNA expression levels(miR-34b,miR-204-5p,and miR-158-5p)and tyrosine protein excitation.We also examined janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathways,along with adverse reactions.Results We detected no significant differences between the two groups with respect the total response rate(P>0.05).Following treatment,the levels of serum CA50,CEA,and CYFRA21-1 in the observation group patients were found to be lower than those of patients in the control group(P<0.05).Similarly,the levels of CD3+,CD4+,CD4+/CD8+in observation group patients were higher than those in the control group patients,whereas the levels of CD8+were lower than those in the control patients(P<0.05).Furthermore,the expression levels of miR-34b,miR-204-5p,and miR-158-5p in the observation group patients were higher than those in the control group patients,whereas contrastingly,the levels of J AK2 and STAT3 mRNA expression were lower than those in the control group(P<0.05).In addition,the progression-free survival of the observation group patients was higher than that of control group patients(P<0.05).Conclusion The combination of endostatin and icotinib has clear therapeutic efficacy in patients with advanced NSCLC,which can con-tribute to enhancing their sensitivity to chemotherapy and immune function.We speculate that the underlying mechanisms of action may be associated with a reduction in the activity of the JAK2/STAT3 signaling pathway,which is beneficial for patient prognosis.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective Non-compliance of active treatments occurred in clinical trials is usually unavoidable,and improper use of standard approaches may lead to biased results,especially for non-inferiority trials.Thus,for three-arm non-inferiority clinical trials,we established a Bayes causal model to estimate causal effects in the presence of non-compliance.Methods Based on the framework of principal stratification,population was stratified according to types of compliance,and the issue was transformed into mixed-distribution identification.Bayes causal model was constructed and data augmentation(DA)algorithm were employed to calculate the posterior distribution of parameters of interest and complete statistical inference.Through simulation,we evaluated performances of our approach,compared with traditional methods including ITT,PP and AT.Results The method of ITT,PP,and AT all had a significant bias when the type of compliance associated with outcomes.The method proposed in this study both had a good performance whether the type of compliance associated with outcomes or not.Conclusion For non-inferiority trials with a high proportion of non-compliance,the method in this article has a better control of the bias.

Objective:To investigate the characteristics of 18F-FDG and 18F-9-fluoropropyl-(+ )-dihydrotetrabenazine (FP-(+ )-DTBZ; short for DTBZ) brain vesicular monoamine transporter type 2 (VMAT2) PET/CT imaging and analyze its clinical diagnostic value in Parkinson′s disease (PD) patients with or without rapid eye movement sleep behaviour disorder (RBD). Methods:From July 2022 to June 2023, 50 patients clinically confirmed with primary PD who underwent 18F-FDG and 18F-DTBZ PET/CT imaging in the First Affiliated Hospital of Zhengzhou University were prospectively collected. Among them, 18 patients with PD accompanied by RBD (PD-RBD(+ ) group; 16 males, 2 females, age (59.2±9.3) years); 32 patients without RBD (PD-RBD(-) group; 16 males, 16 females, age (57.7±10.2) years). Moreover, 10 healthy controls matched with the age of PD patients were included (5 males, 5 females, age (60.3±9.6) years). 18F-DTBZ specific uptake ratio (SUR) of bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra and other brain regions were obtained with occipital cortex as the reference region. Striatal anterior-posterior gradient and other related semi-quantitative indicators were calculated according to the corresponding formula. One-way analysis of variance (the least significant difference (LSD)- t test), Kruskal-Wallis rank sum test (Bonferroni correction), independent-sample t test and Mann-Whitney U test were used to analyze the data. Pearson correlation and Spearman rank correlation analyses were used to evaluate the correlations. ROC curve analysis was also performed. The differences in global glucose metabolism in two groups were compared using statistical parametric mapping (SPM). Results:PD-RBD(+ ) group had a significantly lower Mini-Mental State Examination (MMSE) or PD Sleep Scale (PDSS) score than PD-RBD(-) group ( z values: -3.12, -3.08, both P<0.01), and its contralateral striatal anterior-posterior gradient of the predominantly affected limbs was significantly lower than that in PD-RBD(-) group ( t=-2.73, P=0.009). SPM analysis showed that the glucose metabolism in the contralateral prefrontal lobe was higher than that in the PD-RBD (-) group ( t values: 3.11-3.57, all P<0.001). 18F-DTBZ SUR in the bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra were considerably lower in both groups compared to the healthy control group ( F values: 6.24-147.61, H values: 8.66-24.43, all P<0.05; post-hoc: LSD- t test, Bonferroni correction, all P<0.01). In the PD-RBD(-) group, contralateral striatal anterior-posterior gradient were negatively correlated with unified PD Rating Scale (UPDRS) score and modified Hoehn-Yahr (mH-Y) stage ( r=-0.35, P=0.048; rs=-0.39, P=0.026). The AUC for distinguishing PD-RBD(+ ) and PD-RBD(-) with a contralateral striatal anterior-posterior gradient was 0.706 (95% CI: 0.562-0.851, P=0.016), with the sensitivity and specificity of 59.4%(19/32) and 16/18, respectively. Conclusions:The decrease of contralateral striatal anterior-posterior gradient of VMAT2 is more obvious in patients with PD-RBD(+ ), and there are differences in brain metabolism between the two groups, suggesting that there may be different neuropathological changes and different pathophysiological mechanisms between PD patients with and without RBD. 18F-DTDZ PET/CT can provide imaging basis for the differential diagnosis of the disease subtypes.

ObjectiveTo explore the effectiveness and safety of Yiqi Huoxue Formula （益气活血方， YHF） in the adjuvant treatment of chronic pulmonary heart disease （CPHD） and heart failure （HF）with qi deficiency and blood stasis pattern. MethodsOne hundred and twenty patients with CPHD and HF with qi deficiency and blood stasis pattern were allocated randomly into treatment group and control group， with 60 case in each group. The control group was given conventional basic western medicine， while the treatment group was given oral administration of YHF granules in addition， one dose per day. The treatment course for both groups was 8 weeks. The TCM symptom scores， Minnesota Life Quality Scale （MLHF-Q） scores， echocardiographic indicators including right ventricular end-diastolic diameter （RVEDD）， left ventricular end-diastolic diameter （LVEDD）， left atrial end-diastolic diameter （LAEDD） and pulmonary artery mean pressure （PAMP）， six-minute walking distance （6MWD）， and plasma N-terminal pro-B-type natriuretic peptide （NT-ProBNP） level were compared between the groups. The effectiveness regarding cardiac function and TCM syndromes were compared between the two groups after treatment， and the occurrence of adverse events was observed. ResultsWith two drop-outs both in the treatment group and control group， and 58 cases in each group were included in the outcome analysis. The total effective rate regarding cardiac function and TCM syndromes in the treatment group were 91.38% （53/58） and 96.55% （56/58）， respectively， significantly higher than the corresponding 70.69% （41/58） and 48.27% （28/58） in the control group （P＜0.05）. After treatment， the TCM symptom scores and RVEDD level were significantly reduced in the treatment group， and MLHF-Q score， plasma NT-ProBNP level and PAMP level decreased significantly， while 6MWD increased in both groups （P＜0.01）. Compared to those in the control group， the TCM symptom scores， MLHF-Q score， plasma NT-ProBNP level and PAMP level significantly decreased， while 6MWD increased in the treatment group （P＜0.01）. There were no obvious abnormalities in the blood， urine， stool routine and liver and kidney function indicators in both groups. One adverse reaction each occurred in both groups， and there was no statistically significant difference in the incidence rates（P＞0.05）. ConclusionYHF combined with conventional western medicine can significantly improve the clinical efficacy， improve the clinical symptoms and cardiac function， increase the quality of life and exercise tolerance， and is relatively safe.

Objective To analyze epidemiological characteristics and changing trends of common respiratory infectious diseases among 6-19 year-old population in Shenzhen from 2013 to 2021, and to provide a reference for prevention and control. Methods Data of influenza, mumps and varicella reported cases among the population aged 6-19 years in Shenzhen from 2013 to 2021 were collected, and descriptive methods and Joinpoint regression model were used to analyze epidemiological characteristics and trends of incidences. Results Between 2013 and 2022 in Shenzhen, the average annual incidence rates of influenza, mumps, and varicella among the population aged 6-19 years were 961.44/100 000, 157.70/100 000, and 664.34/100 000 respectively. The incidence of influenza showed an upward trend in 10 years, with an annual percent change (APC) of 52.88% (P<0.05). The incidence of mumps and varicella both showed an 'up-down' trend, with an inflection point in 2019. The incidence APC of mumps were 11.51% and -43.49%, respectively (P>0.05), while the incidence APC of varicella were 28.88% and -50.03%, respectively (P<0.05), respectively. From the point of seasonal distribution, the incidence of three infectious diseases all showed bimodal distribution, with peaks in winter (December to January of the following year) and at the turn from spring to summer (April to June). The proportion of reported cases of three infectious diseases among people aged 6-<10 years old exceeded 60%. The proportion of varicella cases among people aged 10-<15 and 15-19 was on the rise. The incidence rate of influenza and varicella in people aged 15-19 years increased fastest, with APCs of 77.89% and 33.00%, respectively (both P<0.05). Conclusions The trend analysis based on Joinpoint regression model displayed that the reported incidence of influenza among people aged 6-19 years in Shenzhen during 2013-2022 showed an upward trend, and the incidence of varicella had an 'up-down' trend. Children aged 6-<10 years old are the main incidence group, and the prevention and control of infectious diseases in primary schools should be further promoted. Meanwhile, the rapid rise in the incidence of respiratory infectious diseases among people aged 15-19 years old and the increase in the proportion of varicella cases among people aged 10-19 years old suggest that intervention should be carried out to address the influential factors such as immunization gaps and concentrated accommodation in the older age group of minors.

Objective:To analyze the epidemiological features of respiratory syncytial virus (RSV) infection in Beijing, and monitor the sequence variations in RSV glycoprotein (G) gene and clinical features of infected children.Methods:Respiratory tract specimens were collected from children with acute respiratory infection in the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 1, 2023 to December 31, 2023. RSV-positive specimens screened by multiple nucleic acid testing were subjected to PCR to amplify the full-length RSV G gene. A phylogenetic tree was constructed after gene sequencing to analyze RSV subtypes and trace G gene variants. Clinical data were retrieved from the medical record system to analyze the clinical features of children with RSV infection in Beijing.Results:A total of 5 489 respiratory specimens were collected from 3 046 male patients and 2 443 female patients. The average age of the patients was 4.36 years. A total of 589 RSV-positive specimens (10.7%, 589/5 489) were detected with 349 from male patients and 240 from female patients. The average age of children with RSV infection was (2.51±2.78) years and the median age was 0.48 years. RSV had been circulating among children in Beijing since March 2023 with two epidemic peaks in May (24.6%, 122/496) and December (18.2%, 126/693). The predominant subtype of RSV in the first half of 2023 was subtype A, but it was replaced by subtype B from November 2023. Phylogenetic analysis revealed a novel G gene of RSV subtype B (RSV-B-BA9-954bp) with a length of 954 bp, which belonged to a new cluster in the phylogenetic tree. The percentage of patients admitted to the Intensive Care Unit (ICU) was higher in children with new variant of RSV subtype B infection than in those with common RSV subtype B infection [44.1% (15/34) vs 25.2% (31/123), χ 2=4.600, P=0.032], while the counts of white blood cells and the levels of C-reactive protein were lower in the children with new variant infection ( P<0.05). Conclusions:RSV has been prevalent among children in Beijing since March 2023 with two epidemic peaks. The predominant A subtype is gradually replaced by to B subtype. A new variant of RSV B G gene (RSV-B-BA9-954bp) is detected among the children.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. CONCLUSION This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Objective To investigate the action mechanism of cyclic RNA0001287(circ_0001287)and miR-21 in the pathogenesis of diabetic retinopathy(DR).Methods Primary human retinal pigment epithelium(phRPE)cells were iso-lated for circRNA microarray analysis.Arising retinal pigment epithelium(ARPE)-19 cells were cultured in vitro and divid-ed into the blank group,high-glucose group,negative group,si-circ group,circ_0001287 group,circ_0001287+negative group,and circ_0001287+miR-21 group.Small interfering RNA(siRNA)oligonucleotides against circ_0001287,mimics containing miR-21 sequences and miR-21 mimic plasmids were constructed.In the negative group,si-circ group,circ_0001287 group,circ_0001287+negative group and circ_0001287+miR-21 group,the empty plasmid,circ_0001287 siRNA,circ_0001287 mimics,circ_0001287 mimics+miRNA disordered sequence,and circ_0001287 mimics+miR-21 mimic plasmid were transfected into ARPE-19 cells using Lipofectamine 2000 Transfection Reagent.After transfection for 6 h,the Opti-MEM medium was replaced with a fresh normal medium.Cells in the blank group and the high-glucose group were not transfected.Cells in the blank group were cultured with culture solution containing 5.5 mmol·L-1 glucose,and cells in the high-glucose group were cultured with culture solution containing 15.5 mmol·L-1,25.5 mmol·L-1 and 35.5 mmol·L-1 glucose,respectively.Cells in other groups were treated with 35.5 mmol·L-1 glucose for 48 h.The expressions of circ_0001287 and miR-21 were detected by reverse transcription polymerase chain reaction(RT-PCR),cell proliferation activity was detected by Cell Counting Kit-8,and the targeting relationship between circ_0001287 and miR-21 was detected by Dual Luciferase Reporter Assay.RNA immunoprecipitation(RIP)assay and biotin-coupled probe pull-down assay were used to verify the targeting relationship between circ_0001287 and miR-21.Western blot was used to detect protein expression.Re-sults After screening by circRNA,the expression of hsa_circ_0001287 in phRPE cells was significantly reduced.RT-PCR detection showed that compared with the blank group,circ_0001287 expression in ARPE-19 cells in the high-glucose group decreased(P＜0.05)in a dose-dependent manner,and miR-21 expression in ARPE-19 cells gradually increased with the in-crease of glucose concentration(P＜0.05).After co-transfection of siRNA with circ_0001287 mimics,siRNA also reduced circ_0001287 expression,and the relative expression of circ_0001287 in the circ_0001287+negative group(0.70±0.03)was significantly lower than that in the negative group(0.98±0.04,P＜0.05).For cells transfected with the circ_0001287-WT plasmid,compared with the control simulation group(0.98±0.03),the relative luciferase activity of the miR-21 simulation group(0.59±0.02)decreased(P＜0.05).However,for cells transfected with circ_0001287-MUT plasmid,the relative ac-tivity of luciferase was almost the same in the control simulation group(0.96±0.05)and the miR-21 simulation group(1.00±0.04,P＞0.05).In the anti-Ago RIP experiment,miR-21 was significantly enriched in the circ_0001287 group com-pared with the control group,indicating that miR-21 could be significantly pulled down by the biotinylated circ_0001287 probe.Pull-down analysis demonstrated that compared with the control IgG,circ_0001287 specific probe pull-down sam-ples showed significant enrichment of circ_0001287 and miR-21.In this experiment,the cell proliferation rate of the circ_0001287+miR-21 group(78.25％±3.01％)was lower than that of the circ_0001287+negative group(90.88％±3.51％,P＜0.05).Compared with the blank group,the expression of PTEN protein in ARPE-19 cells in the high-glucose group treated with 35.5 mmol·L-1 glucose was significantly down-regulated(P＜0.05),the expression of PTEN protein in ARPE-19 cells in the circ_0001287 group was higher than that in the negative group(P＜0.05),and the expression of PTEN protein in ARPE-19 cells in the circ_0001287+miR-21 group was higher than that in the circ_0001287 group(P＜0.05).Conclusion The expression of circ_0001287 is down-regulated in phRPE cells and high-glucose induced ARPE-19 cells,and up-regulated circ_0001287 can inhibit the injuiy of diabetic RPE cells by adsorption of miR-21 and activation of PTEN expression.

ObjectiveTo screen and validate key enzyme genes affecting the polysaccharide content in different Polygonatum species and perform in-depth amino acid sequence analysis by transcriptomic analysis of P. zanlanscianense， P. kingianum， and P. cyrtonema rhizomes to enrich the transcriptome data of Polygonatum plants and provide references for polysaccharide biosynthesis mechanism and genetic improvement. MethodThe Polygonatum transcriptome was sequenced and analyzed using the Illumina NovaSeq high-throughput sequencing platform， and the differences in the transcriptomes of the three Polygonatum species were compared and according to the annotations of Nr， Gene Ontology （GO）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） databases. The key enzymes in the polysaccharide metabolism pathway were screened， and the expression of key enzyme genes was clustered and correlated with the polysaccharide content. Finally， Real-time polymerase chain reaction （Real-time PCR） was performed to validate the eight key enzyme genes， and the key genes of polysaccharide biosynthesis were further screened for homologous gene sequence analysis in combination with sequencing results， followed by constructing phylogenetic trees， predicting motifs， conserved structural domains， protein sequence isoelectric points， and molecular weights， and constructing 3D protein structures by using homology modeling method. ResultThe annotation of the Nr database revealed that three Polygonatum species had the highest gene homology with Asparagus officinalis. GO database annotation results showed that three Polygonatum species differed significantly in binding， catalytic activity， metabolic processes， and cellular components， while the KEGG pathway annotation results indicated that three Polygonatum species differed significantly in the starch and sucrose metabolic pathway and galactose metabolic pathway. According to clustering analysis， correlation analysis， Real-time PCR， expression profiles， and structural and functional predictions of amino acid sequences， the key enzyme significantly affecting the polysaccharide content in different Polygonatum species was inferred to be β-fructofuranosidase （sacA）. ConclusionSacA may be the main influencing factor for the difference in polysaccharide content of Polygonatum， and is also an important reason why Polygonatum polysaccharides are mainly fructans.