Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Abstract The cooccurrence of multi disease among children and adolescents has become increasingly prominent, necessitating a shift from "single disease separate treatment" to "multi disease co prevention". Focusing on four common health problems in children and adolescents, namely, myopia, depression, overweight/obesity, and spinal abnormalities, the paper systematically reviews the association between four categories of factors, society, environment, family, and individual behavior, and the co occurrence of the aforementioned health problems. The findings indicate that particulate matter 2.5 exposure, light at night, physical inactivity, excessive screen time, and unhealthy diet constitute the primary cross dimensional risk network. Based on these findings, the paper proposes a collaborative action framework involving family, school, and society, emphasizing systematic strategies ranging from upstream environmental governance to downstream behavioral intervention, so as to provide evidence for the practice and policy making of multi disease co-prevention in children and adolescents.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Transoral endoscopic thyroidectomy vestibular approach(TOETVA)has become a research hotspot because of its cosmetic advantages of no scar on the body surface,but there is still a risk of unique complications,among which mandibular sensory dysfunction is the most common,mainly related to mental nerve injury.This review focuses on the key anatomical structures closely related to the establishment of TOETVA space and the occurrence of complications.A deep understanding of the related anatomical structures of maxillofacial region and neck,especially the location and variation of mental nerve,the course of mandibular marginal branches of facial nerve,the level of mandibular muscles and the adjacent relationship of blood vessels,is the key to safely implement TOETVA and reduce postoperative complications.Preoperative image evaluation,intraoperative precise anatomy,following the design of safe area and improving the operation method in the future will contribute to the further promotion of this operation.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Circular RNA(circRNA)is a single-stranded RNA with a covalently closed loop structure,which has a more stable structure and lower immunogenicity than linear RNA.Many studies have shown that circRNA has characteristics such as conservation,stability,and tissue specificity,and can act as a microRNA(miRNA)sponge to interact with proteins and translation templates,and regulate biological functions such as gene expression and signal transduction.Based on the characteristics and various bio-logical functions of circRNA,some endogenous circRNA plays an important regulatory role in the occur-rence and development of tumors and has the potential to be used as biomarkers and therapeutic targets.In addition,mRNA drugs have limitations such as instability,easy degradation,low translation efficien-cy,and immunogenicity in practical applications.Engineered translatable exogenous circRNA can solve some of the limitations of linear mRNA application and become a new type of potential efficient drug.In this paper,we introduce the circRNA biogenesis mechanisms,specific biological functions,and the cur-rent status of diagnosis and treatment applications in tumors.This includes the diagnostic application of endogenous circRNA in tumors,the design and synthesis strategies of exogenous circRNA,and the cur-rent progress in the design and application of engineered circRNA vaccines using their stable and efficient protein expression functions in the treatment of tumors.Finally,we discuss the current clinical diagnostic application problems of circRNA,the challenges of exogenous circRNA therapeutic applications,and the prospects of the field.

Objective To explore the safety of establishing the veno-arterial extracorporeal membrane oxygenation(VA-ECMO)pipeline through percutaneous puncture and the effectiveness of high-risk percutaneous coronary intervention(HR-PCI)under VA-ECMO assistance.Methods In this single-center retrospective study,patients who underwent HR-PCI assisted by VA-ECMO at Wuhan Asian Heart Hospital from December 2022 to December 2023 were included.The primary endpoint was the safety of establishing the VA-ECMO pipeline through percutaneous puncture,mainly characterized by extracorporeal membrane oxygenation(ECMO)-related complications,including severe bleeding/hematoma at the wound,arteriovenous fistula,pseudoaneurysm,peripheral arterial dissection,etc.The secondary endpoint was the effectiveness of HR-PCI under VA-ECMO assistance,defined as major adverse cardiovascular and cerebrovascular events(MACCE)at 6-month follow-up,including the composite events of all-cause death,non-fatal myocardial infarction,repeat revascularization,and ischemic stroke.Results Among the 189 patients included in the study,15(7.9％)had severe bleeding/hematoma at the puncture wound caused by VA-ECMO,8(4.2％)had wound infection,1(0.5％)had arteriovenous fistula,4(2.1％)had pseudoaneurysm,3(1.6％)had peripheral arterial dissection,8(4.2％)had systemic embolism,8(4.2％)had acute kidney injury,3(1.6％)had acute neurological injury,and 1(0.5％)died.percutaneous coronary intervention(PCI)was successful in 182 cases(96.3％),and a total of 36 cases(19.0％)had PCI-related complications.164 patients completed 6-month follow-up,among which 4(2.4％)had all-cause death,11(6.7％)had non-fatal myocardial infarction,11(6.7％)had unplanned repeat revascularization,and 2(1.2％)had the composite event of ischemic stroke.Conclusions Ultrasound-guided percutaneous puncture for establishing the VA-ECMO pipeline has high safety,and HR-PCI patients assisted by VA-ECMO have good short-term effects.

Objective:To study the correlation between coronary artery stenosis of coronary computed tomography angiography(CCTA)and computed tomography fractional flow reserve(CT-FFR)in single cardiac cycle.Methods:A total of 100 patients with highly suspected coronary artery stenosis who visited our hospital from Jan 2023 to Jan 2025 were selected as the study subjects.All patients underwent CCTA examination in single cardiac cycle,and the examination results were input into professional software to assess the degree of CCTA coronary artery stenosis,and CT-FFR values of them were measured and calculated.Results:According to the results of CCTA assessment,there were 15 cases with mild stenosis,61 cases with moderate stenosis,and 24 cases with severe stenosis in 100 patients with suspected coronary artery stenosis.The results of Pearson correlation analysis indicated that there was a negative correlation between CCTA coronary artery stenosis and CT-FFR in single cardiac cycle(r=-0.690,P<0.001).The area under curve(AUC)value of the receiver operating characteristic(ROC)curve of CT-FFR was 0.940(95%CI was 0.892-0.989)in assessing coronary artery stenosis,and the sensitivity,specificity,cutoff value and Youden index of that were respectively 0.776,0.933,0.815 and 0.709.Conclusion:There is a close correlation between the degree of CCTA coronary artery stenosis and CT-FFR in single cardiac cycle,which means the smaller CT-FFR value indicates higher degree of CCTA coronary artery stenosis.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

Objective:The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer(HSPC).Methods:Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chi-nese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups.The patients in the control group were treated with androgen deprivation therapy(ADT).And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group.The baseline data of the two groups were analyzed.After 36 months of treat-ment,the differences between the two groups were compared in terms of overall survival(OS),prostate-specific antigen(PSA)level,PSA response rate,Functional Assessment Scale for Prostate Cancer Therapy(FACT-P),Chinese medicine evidence scores,testoster-one level and safety.Results:A total of 80 study subjects were included in this study,including 42 cases in the treatment group and 38 cases in the control group.There was no statistical difference in the baseline data between the two groups before treatment(P＞0.05).At the end of the observation period,a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months(P＜0.05).There was no statistically signif-icant difference in PSA levels in the treatment group at 3 months(P＞0.05).And the differences in the proportion of PSA50(98.1％vs 91.4％),PSA90(92.9％ vs 84.6％)and the proportion of decrease in PSA(56.7％vs 33.8％)in the treatment group were found compared to those in the control group after 6 months of tre atment.After 12 months of treatment,the scores of FACT-4 and re-nal-yang deficiency in the treatment group were(95.28±7.93)and(15.73±5.70)respectively,compared to the scores in the con-trol group([85.46±10.12]and[18.20±4.27](P＜0.05).However,there was no significant difference in serum testosterone([0.60±0.24]nmol/L vs[1.09±2.10]nmol/L)between the two groups(P＞0.05).After 24 months of treatment,there were significant differences in in the FACT-4 total score([97.95±7.54]vs[80.33±8.58]),renal-yang deficiency syndrome score([14.64±5.15]vs[24.94±8.75])between the treatment group and the control group(P＜0.05).However,there was no signifi-cant difference in serum testosterone([0.73±1.01]nmol/L vs[0.59±0.25]nmol/L)between the two groups(P＞0.05).Bet-ter therapeutic results were showed in the treatment group in terms of total FACT-P score,physical situation score,social and family situation score,emotional state score,functional state score,additional score and renal-yang deficiency symptom score(P＜0.05).After treatment,there was no serious adverse reaction in the course of treatment,and no obvious abnormality was found in the liver and kidney function of the patients from two groups.Conclusion:Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients,and the earlier the intervention,the longer the overall survival of the pa-tients.In addition,this treatment regimen can increase the PSA response rate,improve patients'quality of life,and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.