OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

AIM: To compare the efficacy of highly aspherical lenslets(HAL), defocus incorporated multiple segments(DIMS), and single-vision spectacle lenses(SVL)in slowing myopia progression in children and adolescents.

METHODS: In this retrospective cohort study, myopic children and adolescents aged 6-16 y who were prescribed spectacle lenses at the hospital between January 2023 and June 2023 were included. Participants were divided into the HAL, DIMS, and SVL groups according to the correction modality voluntarily selected by participants and their guardians. The follow-up duration was 12 mo. After 12 mo of wear, changes from baseline in sphere, cylinder, spherical equivalent(SE), axial length(AL), flat corneal curvature(K1), steep corneal curvature(K2), mean corneal curvature, and binocular visual function \〖binocular cross-cylinder(BCC), negative/positive relative accommodation(NRA/PRA)\〗 were compared among the three groups after 12-month spectacle wear. Three groups were further stratified by age into age≤10 y and age>10 y subgroups to explore the effect of age on myopia control efficacy of defocus lenses.

RESULTS: A total of 159 myopic participants(159 eyes; only the right eye was included for each subject)were enrolled. In the HAL group(55 participants), there were 24 males and 31 females, with a mean age of 10.07±2.14 y. The DIMS group consisted of 60 participants(33 males, 27 females), with a mean age of 10.02±1.88 y. The SVL group included 44 participants(21 males, 23 females), with a mean age of 10.59±1.93 y. There were no significant differences in K1, K2, mean corneal curvature, NRA, BCC, and PRA among the three groups after 12-month spectacle wear(all P>0.05). There were statistically significant differences in the changes in sphere, SE, and AL(all P<0.05). The changes in sphere, cylinder, SE, and AL in the HAL and DIMS groups were significantly lower than those in the SVL group(all P<0.0167). The DIMS group showed a significantly smaller cylinder progression than the SVL group(P<0.0167). In participants aged≤10 y, the change in spherical power in the HAL group was significantly smaller than those in the DIMS group and SVL group after 12-month spectacle wear(all P<0.0167). The change in cylindrical power in the DIMS group was smaller than that in the SVL group(all P<0.0167). Among participants aged>10 y, the changes in spherical power, SE, and AL in both the HAL group and DIMS group were significantly smaller than those in the SVL group after 12-month spectacle wear(all P<0.0167).

CONCLUSION: Both HAL and DIMS lenses can effectively slow the progression of refractive error and AL elongation in children and adolescents, without significant adverse effects on binocular visual function. Among children≤10 y, HAL lenses yield superior spherical power control, whereas DIMS lenses provide better astigmatism control than SVL.

Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

Objective To analyze the tumor characteristics associated with achieving pathological complete response(pCR) and tumor prognosis in the patients undergoing laparoscopic rectal cancer surgery after neoadjuvant chemoradiotherapy(nCRT). Methods A retrospective review was conducted on clinical and pathological data of locally advanced rectal cancer(LARC) patients who underwent nCRT at Renji Hospital from January 2017 to January 2024. Factors influencing the achievement of pCR were analyzed, and the patients prognosis of pCR group and non-pCR group was compared. Results Univariate analysis, multivariate Logistic regression analysis, and receiver operating characteristic (ROC) curve analysis showed that tumor length less than 5 cm(cutoff value 5.24 cm) and baseline carcinoembryonic antigen(CEA) less than 5 μg/L(cutoff value 5.33 μg/L) were independent predictors of achieving pCR after nCRT in LARC patients. Prognostic survival analysis showed that the 3-year overall survival(OS) rate for pCR group and non-pCR group were 92.86% and 82.46%, respectively (P=0.193), and the 3-year disease-free survival (DFS) rate were 85.71% and 70.18%, respectively (P=0.141), with no statistically significant differences between the two groups. Conclusions Tumor length and baseline CEA level are independent predictors for achieving pCR after nCRT in LARC patients. Additionally, there were no statistically significant differences in 3-year OS and DFS between pCR group and non-pCR group.

Objective To investigate the effects of exosomes derived from hypoxia-treated mesenchymal stem cells on chondrocyte injury.Methods After mesenchymal stem cells were subjected to hypoxic treatment,the secreted exosomes were collected and co-cultured with IL-1β-stimulated chondrocytes.Cell viability was assessed using the CCK-8 assay,while apoptosis was evaluated by flow cytometry and the measurement of Caspase-3 and PARP activities.Intracellular levels of ROS,Fe2+,and MDA were quantified using commercial assay kits.The expression of GPX4,SLC7A11,and ACSL4 was analyzed at both mRNA and protein levels via qRT-PCR and Western blot,respectively.Additionally,the secretion of COL2A1,MMP13,ADAMTS5,TNF-α,IL-6,and PGE2 was determined by ELISA.Results Chondrocyte viability was significantly enhanced following the uptake of exosomes derived from hypoxia-treated mesenchymal stem cells(H-Exo)(P<0.05).IL-1β treatment reduced chondrocyte viability,increased Caspase-3 and PARP activities,and promoted apoptosis(P<0.05);however,H-Exo effectively reversed IL-1 β-induced apoptotic effects.Furthermore,IL-1 β markedly down-regulated the expression of GPX4 and SLC7A11,up-regulated ACSL4 expression,and elevated intracellular levels of ROS,Fe2+,and MDA(P<0.05),indicating the induction of ferroptosis.Both the ferroptosis inhibitor and H-Exo significantly attenuated IL-1β-triggered ferroptosis,and H-Exo counteracted the detrimental effects of IL-1β as well as those induced by a ferroptosis inducer.Additionally,IL-1β suppressed the expression of the chondrogenic marker COL2A1,up-regulated the catabolic enzymes MMP13 and ADAMTS5,and enhanced the secretion of pro-inflammatory cyto-kines TNF-α,IL-6,and PGE2(P<0.05).Notably,H-Exo alleviated IL-1β-mediated inflammation and restored the balance between chondrogenic anabolism and catabolism.Conclusions Exosomes secreted by mesenchymal stem cells under hypoxic conditions can effectively inhibit chondrocyte apoptosis and ferroptosis,thereby alleviating cellular injury.These findings suggest that such exosomes exert a protective effect on chondrocytes and hold prom-ise as a novel therapeutic strategy for cartilage repair.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets