Objective In this study,the gas exchange performance and impact patterns of microalgae culture based on hollow fiber membrane technology were investigated for the culture of space microalgae.Methods The effects of parameters and conditions such as gas flow rate,membrane area and liquid flow rate on the CO2 fixation efficiency and fixation rate of hollow fiber membrane modules were studied,and the gas exchange performance of different parameters were compared by fitting formula.Results The gas flow rate and membrane area have a significant effect on the gas exchange performance of the module.With the increase of gas flow rate,the fixation rate of CO2 increases at first and then stabilizes,and the fixation efficiency of CO2 shows a continuous downward trend;with the increase of membrane area,the fixation rate and fixation efficiency of CO2 increase significantly,while the liquid flow rate has no significant effect on the gas exchange performance of the module.The highest CO2 fixation rate was 168.24 mg/(L·h)when the membrane area was 0.3m2 and the gas flow rate was 2.0 L/min.Conclusion The use of hollow fiber membrane technology can solve the problem of two-phase flow management in the gas exchange between algae culture and atmosphere,which has a better effect on gas exchange,and can provide reference for the design of gas exchange module of space microalgae photobioreactor.

Objective To compare the curative efficacy of balloon stent kissing technique and jailed wire technique in treating coronary bifurcation lesions(CBL)in the elderly patients.Methods A total of 104 elderly patients with CBL,who received interventional surgery from January 2023 to December 2023 in the First Hospital of Hebei University and Hebei Provincial Hospital of Traditional Chinese Medicine were enrolled in this study.The patients were divided into balloon stent group(n=51,using balloon stent kissing technique)and jailed wire group(n=53,using jailed wire technique).The postoperative changes in diseased vessels,myocardial and endothelial function injuries were compared between the two groups,and the incidence of postoperative major adverse cardiovascular event(MACE)was calculated.Results Half a year after surgery,in both groups the minimum internal diameters of the arterial main branch and lateral branches were larger than their preoperative values(P＜0.05),and the stenosis ratio of the lesion segment was smaller than the preoperative value(P＜0.05).In balloon stent group,the minimum internal diameter of lateral branches was larger than that in jailed wire group(P＜0.05),and the stenosis ratio of the lesion segment was smaller than that in jailed wire group(P＜0.05).Seven days after surgery,in both groups the levels of serum BNP,hs-cTnI,CK-MB,ET-1 and vWF were lower than their preoperative values,while the level of serum NO was higher than its preoperative value.The changes in the above indicators in balloon stent group were more obvious than in jailed wire group.No statistically significant difference in the incidence of MACE existed between the two groups(x2=1.605,P=0.205).Conclusion In treating elderly patients with CBL,both balloon stent kissing technique and jailed wire technique can improve the stenosis degree of the arterial main branch and lateral branches,but balloon stent kissing technique is superior to jailed wire technique in improving postoperative short-term myocardial function and endothelial function.

Objective To explore the neuroprotective effect and related mechanism of electroacu-puncture(EA)combined with tanshinone Ⅱ A(Tan ⅡA)for the treatment of rats with cerebral ische-mia-reperfusion(I/R)injury.Methods Model rats with cerebral I/R were established by the modi-fied Longa suture occlusion method and randomly divided into Model group,EA group,Tan Ⅱ A group,and EA+Tan Ⅱ A group,with 16 rats in each group.Rats in the Sham group(n=16)had their carotid arteries exposed and dissected but not occluded.Neurological deficit score and Morris wa-ter maze test were used to assess neurological impairment and cognitive function in rats.2,3,5-triph-enyltetrazolium chloride(TTC)staining was used to evaluate cerebral infarction volume.Hematoxylin-eosin(HE)staining and TUNEL staining were used to assess neuronal damage in the hippocampus.Western blot was used to detect apoptosis-related proteins and proteins related to the Hippo signaling pathway.Results Compared with the Sham group,the Model group showed increased neurological deficit score,percentage of cerebral infarction area,escape latencies during acquisition training,proportion of TUNEL-positive stained cells in brain tissue,Caspase-3 activity,expression of Cleaved Caspase-3 protein and Bax protein,and decreased expression of time spent in the target quadrant during probe training,the number of platform crossings within 60 s,Bcl-2 protein,Yes-associated protein(YAP),and transcriptional co-activator with PDZ-binding motif(TAZ)protein,and all the differences were significant(P＜0.05).Compared with the Model group,the EA group,Tan Ⅱ A group,and EA+Tan Ⅱ A group showed decreased neurological deficit score,percentage of cerebral infarction volume,escape latencies during acquisition training,time spent in the target quadrant during probe training,number of platform crossings within 60 s,proportion of TUNEL-positive stained cells in brain tissue,Caspase-3 activity,expression of Cleaved Caspase-3 protein and Bax protein,with the EA+Tan Ⅱ A group showing lower values than the EA group and Tan Ⅱ A group,and all the differences were significant(P＜0.05).Compared with the Model group,the EA group,Tan Ⅱ A group,and EA+Tan Ⅱ A group showed increased expression of Bcl-2,YAP,and TAZ proteins,with the EA+Tan Ⅱ A group showing higher protein expression levels than the EA group and Tan Ⅱ A group,and all the differences were significant(P＜0.05).Conclusion The combination of EA and Tan Ⅱ A for the treatment of cerebral I/R injury exhibits synergistic effect,and its mechanism may be related to the inhibition of Hippo pathway activity.

ObjectiveTo analyze the temporal trend of knockdown resistance (kdr) gene mutations highly correlated with pyrethroid resistance in field populations of Aedes aegypti in Jinghong City of Yunnan Province, and to provide a scientific basis for formulating rational insecticide use strategies. MethodsAdult mosquito samples of Aedes aegypti from 2016 to 2023 and larvae mosquito samples from July 2022 to June 2023 were collected in Jinghong City of Yunnan Province. Allele specific PCR (AS-PCR) was used to measure kdr mutations at amino acid positions 989, 1016 and 1534 of the voltage-gated sodium ion channel (VGSC) gene. Data such as mutation rate and mutation allele frequency were calculated, SPSS software was used to perform trend chi square tests on mutation rate and mutation allele frequency with year and month, as well as comparison of mutation allele frequencies and genotype distributions between the dry and rainy seasons, thereby delineating the temporal trend of kdr gene mutations. ResultsAmong the 173 samples collected from 2016 to 2023, the mutation rates of S989P and V1016G were 100.00% for each year, while the mutation rate of F1534C ranged from 62.50% to 100.00%. The mutation rate and mutation allele frequency of F1534C were increased over the years (χ²=22.079, P<0.001; χ²=42.971, P<0.001). Concurrently, the proportion of the PPGGCC genotype was increased annually (χ²=60.790, P<0.001). Among the 288 samples collected from July 2022 to June 2023, the monthly mutation rates for S989P, V1016G, and F1534C were consistently 100.00%. There was only one type of mutation present, namely S989P+V1016G+F1534C. In the combinations of the three genotypes, the SPGGCC genotype accounted for 1.39% (4/288), the PPGGFC accounted for 2.78% (8/288), and the PPGGCC had the highest proportion at 95.83% (276/288). After tesiting the samples collected in August 2023, the mutation rates of 989, 1016 and 1534 sites of VGSC in females, males, and larvae of the same generation were all 100.00%. ConclusionSince 2016, the gene mutations at S989P and V1016G loci in the VGSC gene of wild Aedes aegypti in Jinghong City have remained consistently at 100.00%, while the mutation rate and mutant allele frequency of F1534C have increased year by year during the testing period. By 2023, the mutation rates at three loci in the VGSC gene of Aedes aegypti in Jinghong City had all reached 100.00%, and neither changes in insect developmental stage nor gender differences during transmission exerted a detectable impact on the mutation rates. In the control of Aedes aegypti in Jinghong City, the use of pyrethroid insecticides should be stopped or reduced, and regular monitoring of kdr genes should be carried out to promptly detect new mutations.

BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.

Objective: To determine the latent class of dietary patterns and their association with depressive symptoms among first grade students from multi ethnic middle schools in Yunnan Province, so as to provide a reference basis for promoting mental health among border middle school students. Methods: A cluster random sampling involving 8 500 first grade middle school students from 11 counties in Yunnan Province was conducted by a questionnaire survey between October to December 2022. The Children s Depression Inventory (CDI) was used to assess the depressive symptoms and the Food Frequency Questionnaire was used to collect eating behavior data. The latent profile analysis model was used to fit the latent class of dietary patterns among students. The association between the dietary pattern latent class and depressive symptoms was analyzed by Logistic regression. Results: The depressive symptom detection rate among firstgrade middle school students was 28.3%. Prevalence of depressive symptom in girls (30.9%) was higher than boys (25.5%) with a statistically significant difference ( χ 2=29.83, P <0.01). The dietary patterns among first grade middle school students were classified into four latent classes, as follows:class 1 (low consumption of all dietary components), class 2 (high consumption of fruit, milk and dairy products), class 3 (high consumption of vegetables and meat, and low consumption of processed foods) and class 4 (low consumption of milk, dairy products and eggs, and high consumption of processed foods). After adjusting for confounding variables, the class 3 dietary pattern was negatively correlated with depressive symptoms ( OR=0.62, 95%CI =0.52-0.74) and the class 4 dietary pattern was positively correlated with depressive symptoms ( OR= 1.28 , 95%CI =1.05-1.57) ( P <0.05), compared with the class 1 dietary pattern. Conclusions Multi ethnic first grade middle school students in Yunnan Province follow various dietary patterns. Unhealthy dietary patterns increase the risk of depressive symptoms. The dietary patterns of multi ethnic middle school students in Yunnan Province should be adjusted to promote the establishment of healthy dietary patterns and reduce the risk of depression symptoms in middle school students.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.