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.

Colorectal cancer(CRC),a highly prevalent malignant tumor worldwide,has shown a continuously increasing incidence,particularly with the rise of early-onset CRC in young populations.Neoadjuvant therapy,as an important strategy for locally advanced CRC,shows significant potential to downstage tumors,improve radical surgical cure rates,and enhance prognosis.In this paper,a 39-year-old male patient with sigmoid colon adenocarcinoma at clinical stage cT4aN2aM0(stage ⅢC)is reported.Genetic testing revealed a mutation in the oncogene KRAS(G13D)and microsatellite stability(MSS).The patient also had significantly elevated carcinoembryonic antigen(CEA),lymph node metastasis,and suspected pelvic implant nodules,with a high risk of invasiveness and potential peritoneal metastasis.Because he had a refractory subtype of CRC with poor response to traditional immunotherapy,the patient was treated with neoadjuvant therapy,comprising CapeOx regimen(capecitabine+oxaliplatin),followed sequentially by sluzumab;after 6 treatment cycles,the tumor shrank significantly,and laparoscopic radical sigmoid colon resection was successfully performed,with no residual(ypT0N0)confirmed by postoperative pathology.This case suggests that for patients with KRAS-mutated MSS CRC resistant to traditional immunotherapy,a combination of CapeOx chemotherapy followed by programmed death-1(PD-1)inhibitors may induce a deep pathological response and provide translational treatment opportunities for locally advanced patients.However,the universality and long-term benefits of this treatment regimen still require further longitudinal studies and clinical follow-up.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Colorectal cancer(CRC),a highly prevalent malignant tumor worldwide,has shown a continuously increasing incidence,particularly with the rise of early-onset CRC in young populations.Neoadjuvant therapy,as an important strategy for locally advanced CRC,shows significant potential to downstage tumors,improve radical surgical cure rates,and enhance prognosis.In this paper,a 39-year-old male patient with sigmoid colon adenocarcinoma at clinical stage cT4aN2aM0(stage ⅢC)is reported.Genetic testing revealed a mutation in the oncogene KRAS(G13D)and microsatellite stability(MSS).The patient also had significantly elevated carcinoembryonic antigen(CEA),lymph node metastasis,and suspected pelvic implant nodules,with a high risk of invasiveness and potential peritoneal metastasis.Because he had a refractory subtype of CRC with poor response to traditional immunotherapy,the patient was treated with neoadjuvant therapy,comprising CapeOx regimen(capecitabine+oxaliplatin),followed sequentially by sluzumab;after 6 treatment cycles,the tumor shrank significantly,and laparoscopic radical sigmoid colon resection was successfully performed,with no residual(ypT0N0)confirmed by postoperative pathology.This case suggests that for patients with KRAS-mutated MSS CRC resistant to traditional immunotherapy,a combination of CapeOx chemotherapy followed by programmed death-1(PD-1)inhibitors may induce a deep pathological response and provide translational treatment opportunities for locally advanced patients.However,the universality and long-term benefits of this treatment regimen still require further longitudinal studies and clinical follow-up.

Objective The study aims to investigate the impact of microRNA-874-3p(miR-874-3p)regulation of plakophilin 3(PKP3)on the malignant biological behavior of lung adenocarcinoma cells and its underlying mechanism.Methods Immunohistochemistry and immunocytochemistry were used to detect the expression of PKP3 in lung adenocarcinoma tissue microarray and lung adenocarcinoma cell line A549 cells respectively,and the relationship between PKP3 and clinicopathological features of lung adenocarcinoma patients was analyzed.Select lung adenocarcinoma cell line A549,the experiment was divided into A549 cell group(blank control group),miR-NC group(transfected with miR-NC)and miR-mimics group(transfected with miR-874-3p mimics),sh-NC group(control group transfected with PKP3 silencing plasmid),sh-PKP3 group(transfected with PKP3 silencing plasmid),miR+pcDNA-PKP3 group(transfected with miR-874-3P mimics+pcDNA-PKP3,rescue group)and miR+pcDNA-NC group(transfected with miR-874-3p mimics+pcDNA-NC).The proliferation,invasion,migration and apoptosis of cells in each group were detected.ENCORI database was used to predict the upstream gene of PKP3,and dual luciferase assay was used to detect the targeting relationship between miR-874-3p and PKP3.MAPK/mTOR pathway-related proteins were detected by Western blotting.Results The expression of PKP3 in lung adenocarcinoma tissue was significantly higher than that in adjacent tissues.The high expression of PKP3 was related to clinical stage,tumor size,and lymph node metastasis(P＜0.05).Compared with the human normal lung epithelial cells(BEAS-2B),the expression of PKP3 in A549 cells increased significantly,and the expression of miR-874-3p decreased(P＜0.05).Overexpression of miR-874-3p decreased the PKP3 expression level(P＜0.05).Compared with the control group,both overexpression of miR-874-3p and silenced PKP3 inhibited the cloning and invasion ability of A549 cells,caused cell cycle arrest,and decreased the expression levels of cyclin dependent kinase 4(CDK4),cyclin D1,cyclin E1 proteins in A549 cells(P＜0.05).The expressions of Bax protein and Caspase-3 protein were up-regulated(P＜0.05),and apoptosis increased.Overexpression of PKP3 could reverse the biological behavior of overexpression of miR-874-3p.Overexpression of miR-874-3p and silencing of PKP3 significantly decreased the expressions of P38 MAPK and mTOR phosphorylated proteins.Conclusion MiR-874-3p can negatively regulate PKP3 expression and inhibit the malignant biological behavior of A549 cells through MAPK/mTOR pathway.

High partial pressure oxygen is widely used in the treatment of ischemic and hypoxic diseases and in diving.However,chronic inhalation of gas with high oxygen partial pressure can have a toxic effect on the body,that is,oxygen toxicity.The lung is one of the target organs where injury is the most pronounced and direct after exposure to high partial pressure oxygen.This article reviews the research progress in pathogenesis and diagnosis of pulmonary oxygen toxicity in the hope of providing a reference for related prevention and treatment.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

Objective To study the expression of regulator of cullins-1(ROC1)and ubiquitin binding enzyme 9(UBC9)in non-muscle invasive bladder cancer(NMIBC)and their relationship with clinicopathological features and prognostic value of transurethral resection of bladder tumor(TURBT).Methods Retrospective analysis was conducted on 104 patients with NMIBC who underwent TURBT at Northwest University First Hospital from April 2018 to February 2021.Immunohistochemistry was used to detect the expression of ROC1 and UBC9 in tissues.Follow-up was conducted for 3 years,and Kaplan-Meier curve analysis and COX regression analysis were used to identify factors affecting the prognosis of NMIBC patients.Results The positive rates of ROC1(67.31%)and UBC9(69.23%)in NMIBC cancer tissues were higher than those in adjacent tissues(9.62%,7.69%),and the differences were statistically significant(χ2=73.125,83.200,all P<0.001).There was a positive correlation between the expression of ROC1 and UBC9 in NMIBC cancer(r=0.719,P<0.001).The positivity rates of ROC1(87.23%,90.00%)and UBC9(89.36%,88.33%)in cancer tissues with a maximum tumor diameter of≥2cm,T1 stage were higher than those in cancer tissues with a maximum tumor diameter of<2cm(50.88%,52.63%),Ta/Tis stage(36.36%,43.18%),and the difference were statistically significant(χ2=15.474～33.188,all P<0.05).After TURBT surgery,there were 29 cases of local recurrence,10 cases of metastasis,and 2 deaths of bladder cancer,the 3-year progression-free survival(PFS)rate was 60.58%(63/104).The 3-year PFS of NMIBC patients in the ROC1 positive and negative groups was 47.14%(33/70)and 88.24%(30/34),and the 3-year PFS of patients in the UBC9 positive and negative groups was 47.22%(34/72)and 90.63%(29/32),the differences were statistically significant(Log-rank χ2=15.341,15.931,all P<0.001).Multivariate COX regression analysis showed that ROC1 positivity,UBC9 positivity,maximum tumor diameter≥2cm and T1 phase were risk factors affecting the prognosis of NMIBC patients(all P<0.001).Conclusion The expression of ROC1 and UBC9 is elevated in NMIBC,which is related to the maximum diameter and stage of the tumor.Combined detection of ROC1 and UBC9 can help evaluate the prognosis of NMIBC patients.