Objective: To evaluate the current situation of thermal environment in primary and secondary school classrooms during winter, and to analyze students thermal comfort needs, so as to provide a basis for improving classroom thermal environment. Methods: From December 16 to 26, 2024, a stratified cluster random sampling method was used to select 90 classrooms from 15 primary and secondary schools in centralized/air conditioned heating areas(Liaoning Province, Tianjin City, Shanghai City) and naturally ventilated areas(Anhui Province and Jiangxi Province)for on site environmental measurement. A questionnaire survey was conducted among 743 students. The differences between groups using the χ 2 test were compared. Based on actual measurement data, a predicted mean vote prepared percentage of dissatisfied (PMV-PPD) model for centralized/air conditioned classrooms and an adaptive model for naturally ventilated classrooms were established, and the thermal neutral temperature and comfort interval were calculated. Results: The average outdoor temperature during on site measurement was 4.00(0.20，7.00)℃. In classrooms with centralized or air conditioned heating systems, the measured average temperature was (19.33±2.59)℃, with a thermal comfort range of 20.35-25.35 ℃ and a thermal neutral temperature of 22.85 ℃. And 13.92% of students reported feeling cold, while 80.80% felt comfortable. In classrooms with natural ventilation, the measured average temperature was (12.26±1.83)℃, with a thermal neutral temperature of 19.67 ℃ and a thermal comfort range of 16.17-23.17 ℃. About 48.33% of students reported feeling cold, and 49.81 % felt comfortable.The results of univariate analysis showed that there were statistically significant differences in shoe thickness, temperature sensation, relative humidity sensation and wind speed sensation between centralized/air conditioned heating areas ( χ 2= 7.01 , 31.47, 13.57, 13.80,all P <0.05). There were also statistically significant differences in school stage for primary and secondary school students, body mass index, classroom location for seat, temperature sensation, relative humidity sensation and wind speed sensation between naturally ventilated areas ( χ 2=42.13, 11.13, 11.04, 60.39, 29.27, 38.46,all P <0.05). Conclusions There are differences in thermal environment and students subjective thermal comfort in primary and secondary schools under different ventilation modes in winter. The temperature standards for heated classrooms should be revised, and differentiated environmental regulation strategies should be adopted based on different ventilation methods to improve students health and comfort levels.

ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

Objective To evaluate the efficacy of Yunpi Runtong Formula(composed of Haematitum,Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Alba,Cinnamomi Ramulus,Ophiopogonis Radix,Angelicae Sinensis Radix,Cannabis Fructus,Aurantii Fructus Immaturus,Cimicifugae Rhizoma,Picrorhizae Rhizoma,etc.)in treating functional constipation(FC)of spleen deficiency type in children and to analyze its effects on gut microbiota,defecation patterns,and the serotonin(5-HT)signaling pathway.Methods A total of 160 children with FC of spleen deficiency type treated at Shanxi Institute of Traditional Chinese Medicine from August 2022 to August 2024 were enrolled and randomly divided into a control group and a study group,with 80 patients in each group.The control group received conventional western medicine(lactulose oral solution)treatment,while the study group received Yunpi Runtong Formula treatment in addition to the control group's treatment.Both groups underwent treatment for one month.Changes in traditional Chinese medicine(TCM)syndrome scores,defecation parameters[mean defecation time,spontaneous complete bowel movements(SCBM),Bristol Stool Form Scale(BSFS)],gastrointestinal function markers[substance P(SP),gastrin(GAS),motilin(MLT)],gut microbiota composition,and 5-HT signaling pathway components(serum 5-HT levels,5-HT3R and 5-HT4R protein expression)were analyzed.Clinical efficacy and safety were evaluated.Results(1)The intergroup comparison(by chi-square test)showed that the study group exhibited significantly higher total efficacy[95.00％(76/80)]than the control group[81.25％(65/80);P＜0.01].(2)Both groups exhibited reduced TCM syndrome scores(defecation duration,stool features,difficulty of defecation,interval of defecation,and secondary symptoms;all P＜0.05),with greater improvements in the study group(P＜0.01).(3)After treatment,both groups had shorter mean defecation time,increased SCBM,and higher BSFS scores(all P＜0.05),and the study group demonstrated superior improvements(P＜0.01).(4)Serum SP,GAS,and MLT levels increased in both groups(P＜0.05),with more pronounced elevations in the study group(P＜0.01).(5)Gut microbiota analysis revealed decreased levels of Enterococcus and Enterobacter(P＜0.05)and increased levels of Bifidobacterium and Lactobacillus(P＜0.05)in both groups,with the study group showing significantly greater modulation(P＜0.01).(6)The 5-HT pathway activation(serum 5-HT,5-HT3R/5-HT4R expression)was enhanced in both groups(P＜0.05),more markedly in the study group(P＜0.01).(7)No adverse events or abnormal liver/renal function were observed.Conclusion Yunpi Runtong Formula combined with lactulose effectively alleviates FC symptoms,improves defecation patterns,gastrointestinal function,and gut microbiota,likely via 5-HT pathway activation,with high safety.

This study established the HPLC fingerprints, characteristic chromatograms, and a multi-component content determination method for Bidens bipinnata and B. biternata. The chemical pattern recognition analysis was then employed to clarify the characteristic indexes of quality differences between the two original plants of Bidentis Herba, providing a reference for establishing the quality standards of Bidentis Herba. HPLC was launched on an Agilent Poroshell 120 EC-C_(18) chromatographic column(4.6 mm×250 mm, 4 μm) by gradient elution with a mobile phase of 0.1% aqueous phosphoric acid-acetonitrile at a flow rate of 0.7 mL·min~(-1), detection wavelength of 270 nm, column temperature of 25 ℃, and an injection volume of 5 μL. The similarity between the fingerprints of 18 batches of Bidentis Herba samples and the common pattern(R) ranged from 0.572 to 0.933. A total of 23 chromatographic peaks were calibrated. Through comparison with the reference substances, six components(neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, rutin, and hyperoside) were identified and subjected to quantitative analysis. The characteristic fingerprints of B. bipinnata and B. biternata were calibrated with 20 and 17 characteristic peaks, respectively. Among them, peaks 8, 9, 22, and 23 were the characteristic peaks of B. bipinnata, and peak 7 was the characteristic peak of B. biternata, which can be used to distinguish the two original plants of Bidentis Herba. The relative standard deviation of the content of the above-mentioned six components ranged from 36% to 123%. The cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) classified the 18 batches of Bidentis Herba samples into two categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, three characteristic indexes, rutin, isochlorogenic acid A, and isochlorogenic acid B, were identified. The analytical method established in this study can comprehensively evaluate the consistency of Bidentis Herba samples derived from different original plants, specifically identify the differential components between them, and effectively distinguish the two original plants of Bidentis Herba, providing a basis for the differentiation between different original plants and the quality control of Bidentis Herba.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Bidens/chemistry*

AIM: To compare the effectiveness of foldable capsular body(FCB)with traditional scleral buckling(SB)in the treatment of experimental retinal detachment animal models.METHODS: After successfully establishing rhegmatogenous retinal detachment(RRD)animal models, 24 New Zealand white rabbits were randomly divided into three groups(RRD models group, SB group, and FCB group), with 8 rabbits in each group. The FCB and SB groups underwent SB and FCB surgeries for the RRD animal models, while the RRD models group only consists of RRD models without any surgical intervention during the follow-up period. The follow-up duration was 3 mo. Wide-field neonatal fundus imaging system and ophthalmic B-ultrasound were used to assess the fundus conditions before and after surgery. The Icare® TONOVET Plus tonometer was utilized to evaluate intraocular pressure changes before and after surgery. The Eaton and Draize scoring systems were selected to monitor postoperative inflammatory reactions.RESULTS: The retinal reattachment rates in the FCB and SB groups were 87.5% and 75.0%, respectively, with no statistically significant difference between the groups(P>0.05). The intraocular pressure in both the FCB and SB groups increased postoperatively compared to preoperative levels(P<0.01), and there were no significant differences in intraocular pressure at any time points during the follow-up period between the groups(P>0.05). The intraocular pressure in the RRD models group remained at a low level throughout the follow-up period. The average surgical time for the FCB group was 16.87±2.29 min, which was shorter than 46.25±4.74 min in the SB group(t=-15.166, P<0.001). According to the Eaton and Draize scoring systems, the FCB group had lower grades of conjunctival hyperemia and edema in the early postoperative period compared to the SB group, indicating milder inflammatory reactions(P<0.05).CONCLUSION: Both FCB and SB are effective in treating experimental RRD. Compared to SB, FCB is simpler to operate, and also has a shorter surgical time and milder postoperative inflammatory reactions.

Abstract As a systematic psychological intervention method, bibliotherapy possesses advantages such as low cost, high accessibility, and significant efficacy. The paper systematically reviews the recent research progress of bibliotherapy in the field of adolescent mental health intervention including covering preventive, therapeutic, developmental, personalized, and comprehensive approaches. It discusses the effectiveness and key influencing factors of these interventions. Findings indicate that bibliotherapy can effectively reduce the risk of depressive and anxiety symptoms in adolescents, and improve their emotional regulation skills and social adaptability. Different types of interventions demonstrate varied effects across different populations. Personalized and comprehensive intervention models can further enhance the outcomes, to provide theoretical basis and practical guidance for the development of localized bibliotherapy intervention programs.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Barrett's esophagus(BE),a precancerous state of esophageal adenocarcinoma,poses a major challenge for prevention and treatment owing to its complex mechanism of inflammation-cancer transformation and the lack of effective clinical treatment and torsion strategies.Building upon the"preventing disease progression"theory,this study aimed to address the critical clinical challenge of intercepting the pathological progression during the inflammation-cancer transformation of BE by proposing an innovative"two critical nodes-three stages"pathomechanism framework.The pathogenesis of BE originates from liver depression and qi stagnation.The pathological progression evolves through two critical nodes:liver depression transforming into heat and heat transforming into blood stasis,representing a three-stage evolutionary pattern of qi stagnation,heat transformation,and blood stasis formation.Acidic bile salts,acting as a pathogenic toxin,permeate the entire process and catalyze carcinogenesis.Based on this understanding,the therapeutic principles of"treatment from the liver"and"truncation and torsion"were established,emphasizing stage-specific interventions.For the qi stagnation stage,treatment focuses on soothing the liver and regulating qi,as well as moistening,harmonizing,and descending the qi.This is achieved by combining modified Chaihu Shugan Powder with Xuanfu Daizhe Decoction,while using pungent and drying herbs cautiously and supplementing them with light and floral herbs.In the heat transformation stage,the strategy aims to clear the liver and drain heat while protecting yin and harmonizing the stomach,employing modified Huaganjian combined with Yiguanjian and supplemented with Jinlingzi Powder to clear depressed fire.For the blood stasis formation stage,treatment involves activating blood and resolving stasis,combined with supporting healthy qi and removing toxins.This is achieved using a modified Gexia Zhuyu Decoction,supplemented with Liujunzi Decoction,and additions such as Radix Salviae Miltiorrhizae and turtle carapace to disperse nodules and reduce masses.This theoretical framework establishes a diagnostic and therapeutic model characterized by the integration of disease mechanisms with pathology and the mutual reference of macro-level signs with micro-level indicators.It provides a comprehensive clinical practice pathway,complete with principles,methods,formulas,and herbs,for the stage-specific interception of inflammation-cancer transformation in BE using traditional Chinese medicine.