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.

Objective To explore the effects of growth hormone(GH)on the proliferation,cycle,inva-sion,and migration of colon cancer cells and its possible mechanism.Methods GH3 cells with growth hor-mone-type pituitary adenoma were cultured in vitro,and the secretion of growth hormone in the supernatant of GH3 cells was detected by ELISA.Colon cancer LoVo cells in logarithmic growth phase were randomly divid-ed into the control group and the experimental group.PBS was added to the control group,while high concen-trations of recombinant GH were added to the experimental group.The two groups of cells were cultured in vitro under the same conditions.CCK-8 method was used to detect the proliferation of the cells.Flow cytome-try was used to detect the cell cycle.Transwell assay was used to detect the effect of growth hormone on the invasion and migration of the cells.Western blot was used to detect the expressions levels of E-cadherin,N-cadherin,Vimentin,and Snail-1 proteins in the cells.Results The results of ELISA showed that GH3 cells could secrete a large amount of GH,and the concentration of GH in the supernatant was(1 208±9)ng/mL.GH promoted cell growth in a dose-dependent manner within a certain concentration range,and GH 200 ng/mL was the optimal intervention concentration for subsequent experiments.Compared with the control group,the cell cycle in the experimental group changed from G1 phase to S phase and G2 phase,the ratio of G1 phase cells decreased,and the ratio of S phase cells and G2 phase cells increased(P<0.05).Compared with the control group,the number of the cell invasion and migration increased in the experimental group(P<0.05),the expression levels of N-cadherin,Vimentin,and Snail-1 was up-regulated,while the expression level of E-cadherin was down-regulated(P<0.05).Conclusion High concentration of GH promotes the prolifera-tion,invasion and migration of colon cancer cells,and induces the transition of cell cycle from G1 to S and G2 phases.The mechanism may be related to the epithelial-mesenchymal transition(EMT)of colon cancer cells promoted by high concentration of GH.

Objectives:To analyze the disease burden and changing trends of non-rheumatic valvular heart disease(NRVHD)from 1990 to 2019 in China. Methods:Based on the Global Burden of Disease 2019 database,we collected data related to NRVHD in China from 1990 to 2019,analyzed the crude incidence rate,crude prevalence rate,crude disability-adjusted life year(DALY),and age-scaled rate of NRVHD during this period,and analyzed the corresponding trends.The grey prediction model GM(1,1)was used to predict the disease burden of NRVHD in China from 2020 to 2029. Results:The crude incidence,crude prevalence,and crude DALY rates of NRVHD increased in China from 7.87/100 000,123.21/100 000,and 9.83/100 000 in 1990 to 22.85/100 000,374.16/100 000,and 11.95/100 000 in 2019;the age-standardized incidence rate and the age-standardized prevalence rate increased from 9.22/100 000 and 169.04/100 000 in 1990 to 15.30/100000 and 262.85/100 000 in 2019 respectively,with females being higher than males;the age-standardized DALY rate declined from 13.43/100 000 in 1990 to 9.07/100 000 in 2019,with females being higher than males.Joinpoint regression model analysis showed an increasing trend in the age-standardized incidence rate and age-standardized prevalence rate,and a decreasing trend in the age-standardized DALY rate(annual average percentage change[AAPC]values of 1.86%,1.72%and-1.66%,respectively),trend of change was statistically significant(all P<0.05).The burden of disease for all age groups from 1990 to 2019 showed an overall increasing trend,and the crude incidence rate,crude prevalence rate and crude DALY rate all increased with age,and the elderly group over 60 years old was the main group of disease burden.The results of the grey prediction model showed that by 2029,the age-standardized incidence rate and age-standardized prevalence rate would increase to 18.51/100 000 and 303.26/100 000,respectively,and the age-standardized DALY rate would decrease to 7.42/100 000. Conclusions:From 1990 to 2019,the age-standardized incidence rate and age-standardized prevalence rate of NRVHD in China showed an increasing trend,and the age-standardized DALY rate all showed a decreasing trend.The disease burden of NRVHD in China remains high.Women and the senior population are the main target groups needing special attention in China,and more targeted prevention and treatment strategies are needed for high-risk population.

Objective:To investigate the clinical efficacy of 595-nm pulsed dye laser (PDL) in the treatment of port-wine stains (PWS) in infants and toddlers.Methods:A retrospective analysis was conducted based on clinical data from 155 infants and toddlers with PWS treated with 595-nm PDL at West China Hospital of Sichuan University from January 2013 to October 2023, and the efficacy was evaluated according to pre- and post-treatment photographs. The children were grouped according to gender, age, lesion color, lesion area, lesion sites, and number of treatment sessions, separately, and the differences were analyzed between different groups. Further analysis was conducted to determine factors affecting efficacy of PDL for PWS. Adverse reactions after treatment were recorded. The Mann-Whitney U test and Kruskal-Wallis H test were used to analyze unidirectional ordered R × C contingency table data, the Bonferroni approach was used for multiple comparisons, and multivariate ordered logistic regression analysis was performed for multifactorial analysis. Results:After the treatment with 595-nm PDL, 135 infants and toddlers with PWS showed good response, with an overall response rate of 87.1%. Univariate analysis indicated that the efficacy was associated with the lesion area ( P = 0.016) and the number of treatment sessions ( P < 0.001), but not with age ( P = 0.340), gender ( P = 0.164), lesion color ( P = 0.530), or lesion sites ( P = 0.077), and the smaller the lesion area, the more the treatment sessions, the better the therapeutic effect. Multivariate ordered logistic regression analysis further confirmed the correlations of efficacy with lesion area ( P = 0.010) and number of treatment sessions ( P < 0.001). Adverse reactions occurred in 5 (3.2%) cases of PWS, including 2 (1.3%) of hypopigmentation, 2 (1.3%) of hyperpigmentation, and 1 (0.6%) of scar formation. Conclusion:The 595-nm PDL was safe and effective for the treatment of PWS in infants and toddlers with few adverse reactions, making it a reliable therapeutic option.

Port-wine stains (PWS) are one of the common congenital vascular malformations in dermatology, clinically manifesting as pink or red irregular patches occurring on the skin or mucosa at birth or shortly thereafter, which are often not elevated above the skin surface. In a minority of patients, vascular malformations not only affect the skin, but also involve the eyes, brain, limbs and viscera. These patients are at risk for glaucoma, epilepsy, limb pain, and other clinical conditions. In general, these conditions are referred to as PWS-associated syndromes. These syndromes are rare diseases, can affect multiple systems and exhibit a variety of clinical manifestations, which pose challenges in their diagnosis and treatment. This review focuses on the clinical manifestations, diagnoses, pathogenesis and treatment of PWS-associated syndromes.

Port-wine stains (PWS) are vascular malformations characterized by dilated capillaries and postcapillary venules in the skin. Clinically, they mainly manifest as pink or red irregular patches, most of which may become thickened, darkened in color, or even develop into nodules over age, making treatment more challenging. The mechanisms underlying the development and progression of PWS are not very clear, and may be related to heredity, gene mutations, abnormal ratios of blood vessels to nerves, etc. This review summarizes research progress in the mechanisms underlying the development and progression of PWS, so as to provide a theoretical basis for their treatment.

With advancements in perinatal and neonatal medicine, neonatal mortality rates have significantly decreased, particularly among full-term infants. However, the proportion of preterm infant deaths within neonatal mortality has markedly increased, making preterm infant mortality a critical concern. Due to the wide range of gestational ages among preterm infants, there are significant differences in mortality rates and causes of death depending on gestational age. It is crucial for perinatal medical professionals to recognize the varying mortality rates of preterm infants of gestational ages. In recent years, the mortality rate of late preterm infants in developed countries has been below 2%, with the mortality rate of very preterm infants varying from 1% to 6% depending on their gestational age, while the survival rate of extremely preterm infants of different gestational ages ranges from 60% to 95%. Compared to developed countries, China has achieved a similar mortality rate for late preterm infants, and the mortality rate for very preterm infants is gradually approaching that of developed countries. Nevertheless, there remains a significant gap in the survival rate of extremely preterm infants. This article reviews the characteristics and trends in the survival of preterm infants of different gestational ages both domestically and internationally, aiming to enhance the attention to preterm infant outcomes.

Objective To develop an auto-segmentation model based on no new U-net for delineating high-risk clinical target volume(HR-CTV)and organs-at-risk(OAR)in CT-guided brachytherapy of cervical cancer,and to explore its clinical value.Methods The CT images of 63 patients with locally advanced cervical cancer who had completed image-guided brachytherapy were collected.The HR-CTV and OAR including bladder,rectum and sigmoid colon were delineated manually by a senior oncologist,and the results were taken as the gold standard.The automatic and manual segmentation results were compared,and Dice similarity coefficient was used to evaluate HR-CTV and OAR auto-segmentation accuracies.Results The Dice similarity coefficients of HR-CTV,bladder,rectum,and sigmoid colon were 0.903±0.015,0.948±0.011,0.903±0.008,and 0.803±0.024,respectively.Conclusion The established model can realize the accurate segmentations of HR-CTV,bladder,rectum and sigmoid colon,but the oncologist still needs to scrupulously check the results.

Internal ribosome entry sites (IRESs) are functional RNA elements that can directly recruit ribosomes to an internal position of the mRNA in a cap-independent manner to initiate translation. Recently, IRES elements have attracted much attention for their critical roles in various processes including translation initiation of a new type of RNA, circular RNA (circRNA), with no 5′ cap to support classical cap-dependent translation. Thus, an integrative data resource of IRES elements with experimental evidence will be useful for further studies. In this study, we present IRESbase, a comprehensive database of IRESs, by curating the experimentally validated functional minimal IRES elements from literature and annotating their host linear and circular RNAs. The current version of IRESbase contains 1328 IRESs, including 774 eukaryotic IRESs and 554 viral IRESs from 11 eukaryotic organisms and 198 viruses, respectively. As IRESbase collects only IRES of minimal length with functional evidence, the median length of IRESs in IRESbase is 174 nucleo-tides. By mapping IRESs to human circRNAs and long non-coding RNAs (lncRNAs), 2191 cir-cRNAs and 168 lncRNAs were found to contain at least one entire or partial IRES sequence. IRESbase is available at http://reprod.njmu.edu.cn/cgi-bin/iresbase/index.php.

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.