OBJECTIVE To establish standardized operating procedures,result interpretation guidelines,and clinical application protocols for dust mite-nasal allergen challenge(NAC),and to systematically evaluate its operational reliability and safety.METHODS Patients with positive serum-specific IgE(sIgE)against mites and healthy controls were enrolled between January 2023 and December 2024.Demographic and clinical information was systematically collected.A standardized mite allergen extract was utilized to prepare the challenge solution for all participants.Bilateral synchronous nasal spray challenges were conducted using progressively increasing concentrations(1 000,3 000,10 000,and 30 000 BU/ml).During the challenge,total nasal symptom scores,visual analogue scale,acoustic rhinometry,active anterior rhinomanometry,and four-phase rhinomanometry were assessed,and all evaluation data and diagnostic outcomes were documented accordingly.RESULTS Compared to the baseline measurements,both subjective symptom scores and objective evaluation indicators in patients demonstrated statistically significant changes following NAC(P≤0.001).Among these patients,40 individuals(81.6%)exhibited a positive response to the dust mite-NAC.All healthy control subjects showed negative results in the test.CONCLUSION This study established standardized operating procedures and clinical application guidelines for the dust mite-NAC.These encompass indications,contraindications,preparation of stimulation solutions,procedural steps,operational standards,criteria for positive results,and pre-/post-examination precautions,thereby providing a clinically actionable framework for dust mite-NAC implementation.

Objective To investigate the mechanisms by which miR-23 regulates the PI3K/AKT/mTOR signaling pathway to influence myocardial remodeling,fibrosis,and angiogenesis in hypertensive heart failure(HF)rats.Methods Forty rats were randomly divided into four groups(n=10 per group):a control group,a model group,an antagomir-NC group,and an antagomir-23 group.The HF model was established using a high-salt diet,and intervention was performed via tail vein injection of antagomir-23.Cardiac function parameters,the degree of myocardial fibrosis,cell apoptosis levels,and the expression of angiogenesis-related proteins including CD31,VEGF,and bFGF were measured in each group.Concurrently,the activity of the PI3K/AKT/mTOR signaling pathway was assessed.A dual-luciferase reporter assay was conducted to confirm that miR-23 targets PI3K.Results Inhibition of miR-23 significantly improved cardiac function in hypertensive HF rats,reduced myocardial fibrosis and apoptosis,and enhanced the expression of CD31,VEGF,bFGF,and activated the PI3K/AKT/mTOR signaling pathway in hypertensive HF rats(all P<0.05).The dual-luciferase assay confirmed that miR-23 negatively regulates PI3K expression.Conclusion Inhibition of miR-23 can activate the PI3K/AKT/mTOR signaling pathway,promote angiogenesis,reduce myocardial damage,thereby delaying the progression of hypertensive heart failure.

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Objective　By exploring the function of sulfakinin (SK) and sulfakinin receptor (SKR) of Aedes aegypti, it laid a certain experimental basis and theoretical basis for the research and development of new insecticides targeting neuropeptides and their receptors. Methods　This study investigated the roles of SK and its receptor gene in Ae. aegypti using bioinformatics analysis and Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/Cas9 knockout technology. Subsequently, RNA interference technology was employed to suppress the expression of SK or its receptor in adult mosquitoes. Lastly, transcriptome sequencing technology was utilized to identify and analyze differentially expressed genes between the interference group and the control group in order to gain insights into their functions. Results　It was found that there is only one SK receptor in Ae. aegypti. In addition, during the construction of mutant strains of Ae. aegypti SK and its receptor gene, it was found that only 2% of the G0 generation mutant strains mutated to form chimeras, with a large number of male chimeras dying, and only 14% of female chimeras being able to lay eggs, ultimately resulting in no effective G1 generation mutants. Transcriptome data showed, compared to the control group, 181 genes were significantly differentially expressed after interfering with the SK gene, with 62 genes significantly upregulated and 119 genes significantly downregulated. In addition, after interference with the sulfakinin receptor, 110 genes exhibited significant differential expression, including 20 upregulated and 90 downregulated genes. Cross-analysis of the two datasets identified 46 genes with significant expression changes after interference with sulfakinin or its receptor, with only 4 genes upregulated and the remaining 42 genes significantly downregulated, and the differentially expressed genes were mainly enriched in the metabolic pathway, endocrine system, and digestive system. Conclusions　The SK and its receptor gene are highly conserved and may primarily play roles in regulating the energy metabolism and digestion functions in Ae. aegypti, thus playing an important role in regulating insect growth and development.

Objective To explore the application low of stimulation parameters of transcutaneous electrical acupoint stimulation(TEAS)and transcranial direct current stimulation(tDCS)for post-stroke movement disorders based on data mining.Methods The relevant clinical research literature was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed and Web of Science from January 2000 to May 2023.A database was set up after quality assessment.Frequency analysis,association rules and complex network analysis were used to explore the application law of core acupoints and electrical stimulation parameters.Results A total of 79 articles were included and 128 groups of data were contained.For TEAS,the core acupoints included Waiguan(TE5),Shousanli(LI10),Zusanli(ST36),Hegu(LI4),Neiguan(PC6),Yanglingquan(GB34),etc.,while the most commonly used acupoint combinations of upper limb and lower limb were Shousanli(LI10)-Waiguan(TE5)and Yanglingquan(GB34)-Zusanli(ST36).Among the electrical stimulation parameters of TEAS,the frequencies used vary widely,and 100 Hz was most commonly used,while 2 Hz TEAS was also mainly used for stimulating acupoints located on upper limbs in the treatment of flaccid paralysis.The application of other electrical stimulation parameters was relatively consistent.The bidirectional symmetrical square-wave with 200-250 μs pulse-width was used in majority of studies.The stimulus intensity was mostly determined by patient tolerance.For tDCS,stimulation electrodes were often positioned on the projection of the primary M1,and the safe stimulus intensity was mostly set as 1 to 2 mA.Conclusion In the treatment of post-stroke movement disorders,appropriate acupoints and electrical stimulation parameters of TEAS should be determined on the muscle strength and muscle tension of stroke patients at different stages after stroke,particularly the selection of electric stimulating frequency.

Objective To explore the functional changes of the glial lymphatic system in patients with spontaneous intracerebral hemorrhage(sICH)by MR diffusion tensor imaging(DTI).Methods The clinical and imaging data of 32 sICH patients(sICH group)and 31 healthy volunteers(control group)were retrospectively collected,and the diffusivity values of DTI in different direc-tions were collected from all the subjects,the diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index was calculated,the difference of DTI-ALPS index values between the sICH group and the control group was compared,the changes in the function of the glial lymphatic system in sICH patients were evaluated,and the correlation between DTI-ALPS index and clinical indi-cators in sICH patients was further analyzed.Results The DTI-ALPS index of cerebral hemispheres on the lesions side of sICH group was significantly lower than that on the unaffected side(P＜0.01,t=-5.03),and lower than that on the left side of control group(P＜0.01,t=-9.85)and the right side(P＜0.01,t=-8.80).In addition,vascular endothelial growth factor(VEGF)tes-ting was performed in 8 of the 32 patients,and the levels[(187.40±19.11)pg/mL]were significantly higher than the normal range(0-142.20 pg/mL).Conclusion Through the quantitative analysis of the DTI-ALPS index,the damage to the function of the glial lymphatic system of sICH can be reflected,and perhaps the mechanism of pathophysiological changes in the brain after sICH can be reflected from a new perspective by using MR DTI technology.

Non-small cell lung cancer （NSCLC） is a malignant tumor of the respiratory system with a high incidence. The early symptoms are not typical， and most patients are diagnosed at an advanced stage， which seriously threatens the lives and health of people. Surgery， chemotherapy， and targeted therapy are the main means of treatment at present， but the consequent drug resistance and adverse reactions restrict these treatment methods with certain limitations. In recent years， with the development of traditional Chinese medicine （TCM） in tumor resistance， TCM has attracted extensive attention for its obvious therapeutic effect and fewer adverse reactions. Numerous signaling pathways are involved in the formation and development of NSCLC， where phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway is one of the key regulatory pathways. The PI3K/Akt/mTOR signaling pathway affects the proliferation， invasion， and metastasis of NSCLC cells by affecting the cycle， inhibiting the apoptosis， inhibiting the autophagy of tumor cells， and promoting tumor neovascularization. As revealed by the recent literature， Chinese medicine plays an indispensable role in NSCLC cell autophagy， cell cycle， apoptosis， invasion and metastasis， neovascularization， and reversal of drug resistance by regulating the PI3K/Akt/mTOR signaling pathway. Although some Chinese medicinal extracts or compounds have made great breakthroughs in some mechanisms of action in the treatment of NSCLC， these studies only remain at the level of in vitro cell experiments and animal studies in vivo. Researchers are faced with the great challenge of "transforming the research results of Chinese medicines into clinical applications". Based on the current research status in China and abroad， this paper reviewed Chinese medicine in the intervention in NSCLC through the regulation of PI3K/Akt/mTOR signaling pathway in recent years， in order to open up new ideas for NSCLC drug therapy research and also provide a useful reference for further mechanism research.

Objective:To analyze the distribution of ages at the interhospital transfer of outborn very preterm infants in China and to compare their perinatal characteristics and outcomes at discharge and neonatal intensive care unit (NICU) treatment.Methods:A total of 3 405 outborn very premature infants with a gestational age of 24-31 +6 weeks who were transferred to the NICUs of the Chinese Neonatal Network (CHNN) in 2019 were included in this retrospective study. According to the age at transfer, they were divided into three groups: early transfer (≤1 d), delayed transfer (>1-7 d) and late transfer (>7 d) groups. Analysis of variance, t-test, Chi-square test (Bonferroni correction), Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the general clinical condition, treatment, and outcomes at discharge among the three groups. Results:The median gestational age was 29.7 weeks (28.3-31.0 weeks) and the average birth weight was (1 321.0 ± 316.5) g for these 3 405 infants. There were 2 031 patients (59.6%) in the early transfer group, 406 (11.9%) in the delayed transfer group and 968 (28.4%) in the late transfer group. Infants who received continuous positive airway pressure ventilation and tracheal intubation in the delivery room accounted for 8.4% (237/2 806) and 32.9% (924/2 805), respectively. A total of 62.7% (1 569/2 504) of the mothers received antenatal glucocorticoid therapy and the ratio in the early transfer group was 68.7% (1 121/1 631), which was higher than that in the delayed transfer group [56.1% (152/271), χ2=16.78, P<0.017] and the late transfer group [49.2% (296/602), χ2=72.56, P<0.017]. The total mortality rate of very premature infants was 12.7% (431/3 405), and the mortality rates in the early, delayed and late transfer groups were 12.4% (252/2 031), 16.3% (66/406) and 11.7% (113/968), respectively ( χ2=5.72, P=0.057). The incidences of severe intraventricular hemorrhage, late-onset sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge were all higher in the delayed and late transfer groups than in the early transfer group, respectively. The incidences of retinopathy of prematurity, retinopathy of prematurity requiring treatment and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge in the late transfer group were significantly higher than that in the delayed transfer group (Bonferroni correction, all P<0.017). In the late transfer group, the median age of very premature infants at discharge was 66.0 d (51.0-86.0 d), and the corrected gestational age at discharge was 38.9 weeks (37.1-41.2 weeks), and both were greater than those in the early transfer [48.0 d (37.0-64.0 d), Z=260.83; 36.9 weeks (35.7-38.3 weeks), Z=294.32] and delayed transfer groups [52.0 d (41.0-64.0 d), Z=81.49; 37.4 weeks (36.1-38.7 weeks), Z=75.97] (all P<0.017). Conclusions:Many very premature infants need to be transferred to higher-level hospitals after birth. The later the very premature infants are transferred, the higher the incidence of complications will be. It is suggested that intrauterine or early postnatal transport may improve the prognosis of very premature infants.

{L-End}Objective To investigate the influencing factors of work-related musculoskeletal disorders (WMSDs) that affect neck-shoulder-back among manufacturing workers. {L-End}Methods A total of 8 250 front-line workers from 27 manufacturing enterprises in Henan Province and Hubei Province were selected as the research subjects using cluster sampling method. The Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of neck-shoulder-back (include neck, shoulder, upper back, and lower back) WMSDs in the past year. The log-binomial model, principal component analysis (PCA) and multivariate logistic regression analysis were used to analyze the influencing factors of WMSDs in the neck-shoulder-back. {L-End}Results The prevalence of WMSDs was 77.2%. The prevalence of neck-shoulder-back WMSDs was 50.9%. The prevalence ratios of WMSDs were relatively higher among the neck, shoulder, and upper back (all P<0.05). The results of PCA improved logistic regression analysis showed that the influencing factors of neck-shoulder-back WMSDs were individual factors, biomechanical factors, psychosocial factors and environmental factors. In terms of individual factors, the risk of neck-shoulder-back WMSDs was higher in females than in males (P<0.05). With the increase of age, length of service, and education level, the risk of neck-shoulder-back WMSDs increased among manufacturing workers (all P<0.05). The risk of neck-shoulder-back WMSDs of workers in textile, clothing, shoes and hats manufacturing industry was relatively lower than that in the other nine industries (all P<0.05). In terms of the biomechanical factors, spending a lot of effort to operate tools/machines, sitting for a long time at work,bending greatly bending and turning at the same time, neck leaning forward or maintaining this posture for a long time, neck twisting or maintaining this posture for a long time and uncomfortable position resulting in difficulty exerting exertion were all risk factors of neck-shoulder-back WMSDs among manufacturing workers (all P<0.05) Bending slightly for a long time was a protective factor for neck-shoulder-back WMSDs among manufacturing workers (P<0.05). In terms of the psychosocial factors, doing the same work every day, self-determination in resting time between works staff shortage, and frequent overtime work were risk factors for neck-shoulder-back WMSDs among manufacturing workers (all P<0.05). Adequate resting time was a protective factor for neck-shoulder-back WMSDs among manufacturing workers (P<0.01). In terms of environmental factors, working under cold or fluctuating temperature, having nothings to lean on, and soles slipping or falling at work were all risk factors for neck-shoulder-back WMSDs among manufacturing workers (all P<0.05). {L-End}Conclusion Manufacturing workers are prone to suffer from neck-shoulder-back WMSDs. The influencing factors include individual factors, biomechanical factors (force load and static load), psychosocial factors and environmental factors.

{L-End}Objective To explore the interaction between social psychology and workload factors on neck work-related musculoskeletal disorders (WMSDs) in manual workers. {L-End}Methods Manual workers in Henan Province and Hubei Province were selected as the research subjects using typical sampling method. The Chinese Musculoskeletal Questionnaire was used to investigate the prevalence of neck WMSDs in the research subjects. A total of 4 327 workers with neck WMSDs were selected as the case group, and 4 327 workers without neck WMSDs were selected as the control group in a 1∶1 pairing. Conditional logistic regression analysis was used to compare the relevant risk factors in the two groups, and the additive interaction model was established to analyze the interactions between the risk factors. {L-End}Results The univariate conditional logistic analysis results showed that dynamic load, static load, power load and psychosocial factors increased the risk of neck WMSDs in manual workers (all P<0.05). In terms of the social psychological factors, insufficient rest time had the greatest impact workers, with the odds ratio (OR) and 95% confidence interval (CI) of 1.799 (1.647-1.965). In terms of dynamic load, static load and power load, repeated similar movements of the head per minute (bending, twisting), forward bending of the neck or maintaining this posture for a long time, and lifting heavy objects>20 kg had the greatest impact, with the OR and 95%CI of 1.599 (1.470-1.739), 1.984 (1.805-2.181) and 1.241 (1.093-1.408), respectively. There was a synergistic interaction between insufficient rest time and forward bending of the neck or maintaining this posture for a long time, and the relative excess risk due to interaction (95%CI) and attributable proportion (95%CI) were 0.420 (0.187-0.652) and 0.171 (0.066-0.276), respectively. There is no interaction between insufficient rest time and repeated similar movements of the head per minute (bending, twisting), and lifting heavy objects >20 kg. {L-End}Conclusion The interaction between insufficient rest time and forward bending of the neck or maintaining this posture for a long time (static load) can increase the risk of neck WMSDs in manual workers, which is an additive synergistic effect.