AIM:To assess the efficacy of intravitreal conbercept for treating neovascular age-related macular degeneration(nAMD)under a treat-and-extend(T & E)regimen.METHODS: A retrospective analysis was conducted on nAMD patients followed over a 2-year period(May 2020 to May 2022). All eyes received three monthly loading intravitreal injections of conbercept, followed by a T& E regimen in which the injection interval was extended by 2 or 4 wk according to disease activity, up to a maximum of 16 wk. When disease activity recurred, the interval was shortened. Patients were divided into initial and non-initial treatment groups based on treatment history. Best-corrected visual acuity(BCVA), central macular thickness(CMT), injection frequency, and intervals between injections over the 24-month follow-up were compared.RESULTS:Totally 27 patients(15 males and 12 females, 33 eyes)were enrolled. In the initial treatment group(18 eyes, mean age 65.72±12.32 y), BCVA significantly improved at 1, 3, and 6 mo(P<0.05), and CMT significantly improved at 1 and 3 mo(P<0.05). In the non-initial treatment group(15 eyes, mean age 69.00±9.21 y), BCVA improved significantly at 3 mo(P<0.05), whereas CMT remained stable(P >0.05). Baseline CMT was similar between the groups(P>0.05). However, significant differences were observed at multiple post-injection time points(P<0.05). The total number of injections did not differ between the groups(P>0.05). Intervals between injections varied, with the majority at 4 and 3-4 mo in the initial and non-initial treatment groups, respectively.CONCLUSION:Initiating intravitreal conbercept therapy under a T & E regimen results in superior visual and anatomical outcomes compared with non-initial treatment.

OBJECTIVE To explore the improvement effects of Suting pingchuan decoction （STPC） on bronchial asthma in rats and its potential mechanism. METHODS Male SD rats were randomly divided into blank group， model group， STPC low-， medium- and high-dose groups （4.14， 8.28， and 16.56 g/kg， respectively， based on the crude drug dosage）， and dexamethasone group （positive control， 1 mg/kg）， with 8 rats in each group. Except for the blank group， the other groups were sensitized by intraperitoneal injection of ovalbumin and challenged by nebulized inhalation of ovalbumin to establish a bronchial asthma model. From the day of nebulization challenge， rats of each group were administered the corresponding drug solution or normal saline by gavage 1 hour before aerosolization， once a day， for 7 consecutive days. During the experiment， behavioral changes in rats of each group were observed. After the last administration， the levels of inflammatory factors （interleukin-1β， interleukin-18） in bronchoalveolar lavage fluid （BALF）， and oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] in lung tissue were determined； pathological changes in lung tissue were observed； cell apoptosis in lung tissue， and the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） and the protein expressions of NLRP3， cleaved caspase-1， caspase-1， gasdermin D （GSDMD） and gasdermin D-N-terminal domain （GSDMD-N） in lung tissue were detected. RESULTS Compared with the blank group， rats in the model group showed symptoms such as scratching their ears and noses and frequent sneezing； the lung tissue structure was severely damaged， and there was obvious inflammatory cell infiltration. The levels of inflammatory factors in BALF， as well as the level of MDA， TUNEL-apoptotic cell rate， the mRNA expression of NLRP3， and the protein expressions of NLRP3， cleaved caspase-1， caspase-1， GSDMD-N and GSDMD in lung tissue were significantly increased or up-regulated， while the level of SOD in lung tissue was significantly decreased （ P ＜0.05 or P ＜0.01）. Compared with the model group， the above symptoms and pathological damages of lung tissue in each drug group were significantly improved， and all quantitative indicators （except for the protein expressions of GSDMD in the STPC groups， as well as the level of SOD， and the protein expressions of cleaved caspase-1， caspase-1 and GSDMD-N in the STPC low-dose group） were significantly reversed （ P ＜0.05 or P ＜0.01）. CONCLUSIONS STPC can improve airway inflammation and lung tissue damage in rats with bronchial asthma， reduce the level of oxidative stress， and decrease the release of inflammatory factors such as IL-1β and IL-18. Its mechanism of action may be related to the inhibition of pyroptosis activation mediated by the NLRP3/caspase-1/GSDMD signaling pathway.

ObjectiveTo explore the effects and mechanism of the modified Danggui Yinzi on "itch-anxiety" model rats of chronic urticaria （CU）. MethodsThe 36 SPF-grade 6-8-week-old female SD rats were randomly divided into a blank control group，a model group，a positive control group，a low-dose modified Danggui Yinzi group，a medium-dose modified Danggui Yinzi group，and a high-dose modified Danggui Yinzi group. A "itch-anxiety" model was established by intraperitoneal injection of a suspension of sodium chloride and aluminum hydroxide and ovalbumin，combined with chronic unpredictable emotional stress stimulation. After successful modeling，rats in each group were administered drugs by gavage. The positive control group was given intragastric administration of the drug solutions of cetirizine and fluoxetine （2.08 mg·kg^-1·d^-1 fluoxetine， 2 mg·kg^-1·d^-1 cetirizine）， the low-，medium-，and high-dose modified Danggui Yinzi groups were administered traditional Chinese medicine at 1.44，2.88， 5.76 g·kg^-1， respectively，while the blank control group and model group were given an equal volume of normal saline. All interventions lasted for 15 days. Behavioral changes were evaluated by the elevated plus-maze test （detecting the percentage of entries into the open arms （OE%），the percentage of time spent in the open arms （OT%），and the total number of entries into the open and closed arms （TNE）），the open-field test （detecting total activity，average movement speed，and latency to enter the central area），and scratching behavior observation. Pathological changes of skin tissues were observed by hematoxylin-eosin （HE） staining and toluidine blue staining，while those of amygdala tissues were observed by HE staining，Nissl staining，and immunofluorescence detection of ionized calcium-binding adapter molecule-1 （Iba-1）. The content of immunoglobulin E （IgE），interleukin-33 （IL-33），histamine in serum and glutamate in the amygdala was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of striatal-enriched protein tyrosine phosphatase （STEP），N-methyl-D-aspartate receptor subunit 2B （NR2B）， calmodulin-dependent protein kinase Ⅱ （CaMKⅡ），phosphorylated CaMKⅡ （p-CaMKⅡ），mitogen-activated protein kinase （MAPK），phosphorylated MAPK （p-MAPK），nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB），phosphorylated NF-κB （p-NF-κB），and postsynaptic density protein-95 （PSD-95） in the amygdala. ResultsCompared with the blank control group，the model group rats showed obvious anxiety-like behaviors （decreased OE%，OT%，and TNE，reduced total activity，slower average movement speed，and prolonged latency to enter the central area），increased scratching times，obvious skin inflammation and mast cell degranulation，severe amygdala tissue damage，increased glutamate content in the amygdala，and elevated levels of IgE and IL-33 in serum. The expression of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala increased，while the expression of PSD-95 protein decreased （P<0.05）. Compared with the model group，the modified Danggui Yinzi group of each dose had increased OE%，OT%，TNE，total activity，and average movement speed，shortened latency to enter the central area， reduced scratching times，alleviated skin inflammation and mast cell degranulation，relieved amygdala tissue damage，decreased glutamate content in the amygdala，and reduced levels of IgE and IL-33 in serum. Moreover，compared with the model group，the low -，medium-，and high-dose modified Danggui Yinzi groups showed decreased expression levels of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala，and increased expression of PSD-95 protein. There was a significant dose-effect relationship，with the high-dose group showing the most significant regulatory effect （P<0.05）. ConclusionThe modified Danggui Yinzi has a therapeutic effect on "itch-anxiety" model rats of CU. Its mechanism may be related to regulating glutamate metabolism in the amygdala，modulating the STEP/NR2B/CaMKⅡ/MAPK/NF-κB pathway，and regulating the expression of PSD-95.

Objective: To identify the latent profile characteristics and associated factors of family intergenerational transmission of proactive health behaviors in overweight and obesity junior high school students, so as to provide a reference for promoting active health in adolescents. Methods: From October to December 2024, a stratified cluster random sampling method was employed to select 4 932 junior high school students with overweight and obesity from 18 junior high schools of three cities representing the eastern (Yantai), central (Zibo), and western (Zaozhuang) regions of Shandong Province. Latent profile analysis was used to explore the heterogeneity of family intergenerational transmission among those students. Univariate analysis and multiple Logistic regression analysis were conducted to identify factors associated with different profiles and to examine the influence of profile membership on junior high school students proactive health levels. Results: The intergenerational transmission of health behaviors in junior high school students could be classified into 3 latent profiles:the moderate modeling dysfunctional group (5.88%, n =290), the low modeling advantage deficient group (41.79%, n =2 061), and the high modeling functional harmonious group ( 52.33 % n =2 581). Univariate analysis showed that gender, urban/rural area, region location, paternal/maternal education level, family economic status, and only child status were significantly associated with the classification of latent profiles of intergenerational transmission in families of overweight and obesity junior high school students ( χ 2=7.63-165.22, all P <0.05). Multiple Logistic regression analysis revealed that, using the moderate modeling dysfunctional group as the reference, male students ( OR =0.71) and those residing in coastal cities ( OR =0.74) were less likely to belong to the low modeling advantage deficient group (both P <0.05); students with moderate family economic status were more likely to belong to the low modeling advantage deficient group ( OR =1.72， P <0.05). Conversely, students living in urban areas ( OR =1.43), those with fathers ( OR =2.53) or mothers ( OR =2.48) having a college degree or above, and those with moderate ( OR =3.89) or good ( OR =2.42) family economic status were more likely to be classified into the high modeling functional harmonious group (all P < 0.05 ). Using the low modeling advantage deficient group as the reference, residing in coastal cities ( OR =1.26), living in urban residence ( OR =1.14), having parents (father or mother) with a college education or above ( OR =1.91, 2.33), moderate or good family economic status ( OR = 2.27 , 3.17), and being an only child ( OR =1.19) were associated with a higher probability of belonging to the high modeling functional harmonious group (all P < 0.05 ). There was a statistically significant difference in active health behaviors among students across different latent profiles of family intergenerational transmission ( F =494.79, P <0.01). Conclusions The heterogeneity of family intergenerational transmission is associated the level of proactive health behaviors among junior high school students. Therefore, precision interventions should be implemented based on different categories of family intergenerational transmission, so as to strengthen the efficacy of intergenerational transmission of health behaviors and promote proactive health among junior high school students.

Vancomycin is a glycopeptide antibiotic widely used for severe infections caused by gram-positive bacteria. Nevertheless， its clinical application is limited by a narrow therapeutic window and inter-individual differences in pharmacokinetics. Conventional dosing regimens rely on clinical experience and population pharmacokinetic models， which make precise therapy difficult. The emergence of machine learning provides new insights into tackling the above challenges. By integrating multi-dimensional data including demographic characteristics， clinical indicators and combined medications， machine learning can assist individualized medication for patients and improve the capacity for vancomycin dose prediction， in vivo exposure assessment and renal toxicity risk warning. However， the application of machine learning still faces multiple challenges such as poor data quality， weak model generalization ability and insufficient interpretability. Its clinical value needs to be further confirmed by prospective studies and external validation. Future research may consider deep integration of machine learning and population pharmacokinetic models to better support vancomycin individualized medication.

ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.

At present, there is no effective drug treatment for obstructive sleep apnea hypopnea syndrome (OSAHS). It is usually treated by mechanical ventilation through a ventilator. In this paper, a non-invasive bi-level breathing therapy system suitable for home scenarios is developed. The system supports single-level and bi-level positive airway pressure therapies, and introduces the function of inspiratory synchronous trigger based on flow monitoring to enhance the synchrony of patient-ventilator synchronization. The test results show that the performance indicators of the system meet expectations. Each ventilation mode can operate normally and can meet the requirements for the use of home non-invasive ventilators.
Humans ; Sleep Apnea, Obstructive/therapy* ; Equipment Design ; Noninvasive Ventilation/instrumentation* ; Respiration, Artificial

Objective To explore the prognostic value of serum growth hormone releasing peptide(Ghre-lin),angiopoietin like protein 4(ANGPTL4)combined with Geriatric Nutritional Risk Index(GNRI)in eld-erly patients with chronic pulmonary heart disease(CPHD).Methods From January 2019 to January 2022,a total of 98 elderly patients with CPHD admitted to the Hai'an People's Hospital were selected as the CPHD group,and another 98 healthy individuals who underwent physical examinations were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to determine the levels of serum Ghrelin and ANGPTL4.Multivariate Logistic regression was applied to analyze the influencing factors of prognosis in elderly patients with CPHD.Receiver operating characteristic(ROC)curve was plotted to analyze the predic-tive value of serum Ghrelin,ANGPTL4 combined with GNRI in the prognosis of CPHD.Results Compared with the control group,the level of serum Ghrelin and GNRI in the CPHD group were obviously reduced(P＜0.05),while the level of ANGPTL4 was obviously increased(P＜0.05).Compared with the survival group,the GNRI and Ghrelin level in the death group were obviously reduced(P＜0.05),while the level of AN-GPTL4 was obviously increased(P＜0.05).Multivariate Logistic regression results showed that ANGPTL4 was a risk factor affecting the prognosis of elderly CPHD patients(P＜0.05),while Ghrelin and GNRI were protective factors affecting the prognosis of elderly CPHD patients(P＜0.05).ROC curve results showed that the combination of serum Ghrelin,ANGPTL4,and GNRI had the largest area under the curve(AUC)in predicting the prognosis of elderly CPHD patients,which was better than that of the individual predictions of serum Ghrelin,ANGPTL4,and GNRI(P＜0.05).Conclusion The level of serum Ghrelin decreases and the level of ANGPTL4 increases in elderly patients with CPHD.The combination of the two with GNRI could better predict the prognosis of CPHD patients and has high predictive value.