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.

ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: To investigate the effects of the combined Yiqi Huoxue Jiedu formula (YHJF) on intestinal microbiota in elderly patients with pulmonary-derived sepsis and identify potential microbial targets. METHODS: A prospective randomized double-blind controlled trial was conducted. Elderly patients with pulmonary infection-induced sepsis admitted to the emergency department of Guangdong Provincial Hospital of Traditional Chinese Medicine (TCM), intensive care unit (ICU) of Fangcun Hospital, and ICU of Daxuecheng Hospital, from November 2020 to October 2021 were enrolled and randomized into two groups. Both groups received conventional Western medicine treatment. The observation group additionally received YHJF (composed of 15 g of Panax ginseng, 9 g of Panax notoginseng, and 3 g of Rheum palmatum, dissolved in 50 mL warm water) orally or via nasogastric tube twice daily for 7 days; while the control group received a placebo. Clinical data and fresh fecal samples were collected before treatment and on days 5-7 of treatment. Intestinal microbiota diversity and structure were analyzed via 16S rDNA sequencing and bioinformatics [α diversity, β diversity, and linear discriminant analysis effect size (LEfSe)]. RESULTS: Fifty-five patients were included (29 in the control group, 26 in the observation group). There were no significantly differences in gender, age, comorbidities, and baseline sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), acute gastrointestinal injury (AGI) classification score, and gastrointestinal failure (GIF) score between the two groups. Compared to the control group, the observation group showed significantly lower serum procalcitonin, APACHE II score, and greater reduction in GIF score by day 7. Thirty fecal samples were collected pre-treatment (baseline group), 29 post-treatment from the control group, and 26 from the observation group. Gut microbiota α diversity analysis revealed that Simpson index in the observation group and control group were significantly decreased compared to the baseline group [0.75 (0.53, 0.91), 0.81 (0.32, 0.91) vs. 0.88 (0.87, 0.89), both P < 0.05], but there was no significantly difference between the observation group and the control group. There were no significantly differences in Chao1, Ace, and Shannon indices among three groups. β diversity analysis indicated that distinct microbiota structures among three groups (R² = 0.096, P = 0.026). Species difference analysis showed that, at the phylum level, Firmicutes (53.69%), Actinobacteria (16.23%), Proteobacteria (15.39%), and Bacteroidetes (9.57%) dominated, with no significant intergroup differences. At the genus level, 38 taxa showed significant differences. Compared to the control group, the observation group exhibited increased Erysipelatoclostridium (P = 0.014) and Faecalibacterium (P = 0.013), and decreased Bacteroides (P = 0.009), Bilophila (P = 0.005), Eggerthella (P = 0.002), and Collinsella (P = 0.043). LEfSe analysis highlighted Lactobacillus salivarius, Erysipelatoclostridium, Collinsella, Cloacibacillus, and Bacteroides as key discriminators. CONCLUSION YHJF combined with conventional therapy alters intestinal microbiota structure in patients with elderly pulmonary-derived sepsis, with Bacteroides, Erysipelatoclostridium, and Collinsella identified as potential microbial targets.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Double-Blind Method ; Sepsis/drug therapy* ; Aged ; Prospective Studies ; RNA, Ribosomal, 16S/genetics* ; Male ; Female ; Panax notoginseng ; Rheum

Objective To evaluate the diagnostic value of transrectal contrast-enhanced ultrasound (CEUS) for rectal cancer with intestinal stenosis caused by tumors. Methods Forty-nine patients with rectal cancer underwent transrectal CEUS and magnetic resonance imaging (MRI) before surgery.Intraoperative tumor localization and postoperative pathological results were taken as the gold standard for diagnosis.The differences in T stage,localization,and tumor length of rectal cancer were compared between the two methods. Results The total accuracy rates of transrectal CEUS and MRI in diagnosing T stage were 75.5% (36/49) and 67.3% (33/49),which had no significant difference (χ²=0.8,P=0.371).The total accuracy rates of transrectal CEUS and MRI in judging tumor localization were 79.5% (39/49) and 77.5% (38/49),which had no significant difference (χ²=0.061,P=0.806).The measurement results of tumor length in pathological examination had no significant difference from the transrectal CEUS results (t=1.42,P=0.162) but a significant difference from the MRI results (t=3.38,P=0.001).Furthermore,transrectal CEUS detected 8 (16.3%) cases of colonic polyps among the 49 patients,while MRI did not detect colon lesions. Conclusions Transrectal CEUS has good consistency with MRI in T staging and localization judgement of rectal cancer with intestinal stenosis,and this method can more accurately evaluate the tumor length and simultaneously evaluate whether there is a lesion in the entire colon at the proximal end of stenosis.It can be used as a supplementary examination before rectal cancer treatment in clinical practice.
Humans ; Rectal Neoplasms/complications* ; Male ; Middle Aged ; Female ; Aged ; Contrast Media ; Ultrasonography ; Adult ; Magnetic Resonance Imaging ; Constriction, Pathologic/diagnostic imaging* ; Aged, 80 and over ; Intestinal Obstruction/etiology*

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

BACKGROUND: The urban-rural disparities in overweight and obesity among children and adolescents are narrowing, and there is a need for long-term and updated data to explain this inequality, understand the underlying mechanisms, and identify priority groups for interventions. METHODS: We analyzed data from seven rounds of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted from 1985 to 2019, focusing on school-age children and adolescents aged 7-18 years. Joinpoint regression was used to identify inflection points (indicating a change in the trend) in the prevalence of overweight and obesity during the study period, stratified by urban/rural areas and sex. Annual percent change (APC), average annual percent change (AAPC), and 95% confidence interval (CI) were used to describe changes in the prevalence of overweight and obesity. Polynomial regression models were used to predict the prevalence of overweight and obesity among children and adolescents in 2025 and 2030, considering urban/rural areas, sex, and age groups. RESULTS: The prevalence of overweight and obesity in urban boys and girls showed an inflection point of 2000, with AAPC values of 10.09% (95% CI: 7.33-12.92%, t = 7.414, P <0.001) and 8.67% (95% CI: 6.10-11.30%, t = 6.809, P <0.001), respectively. The APC for urban boys decreased from 18.31% (95% CI: 4.72-33.67%, t = 5.926, P = 0.027) to 4.01% (95% CI: 1.33-6.75%, t = 6.486, P = 0.023), while the APC for urban girls decreased from 13.88% (95% CI: 1.82-27.38%, t = 4.994, P = 0.038) to 4.72% (95% CI: 1.43-8.12%, t = 6.215, P = 0.025). However, no inflection points were observed in the best-fit models for rural boys and girls during the period 1985-2019. The prevalence of overweight and obesity for both urban and rural boys is expected to converge at 35.76% by approximately 2027. A similar pattern is observed for urban and rural girls, with a prevalence of overweight and obesity reaching 20.86% in 2025. CONCLUSIONS The prevalence of overweight and obesity among Chinese children and adolescents has been steadily increasing from 1985 to 2019. A complete reversal in urban-rural prevalence is expected by 2027, with a higher prevalence of overweight and obesity in rural areas. Urgent action is needed to address health inequities and increase investments, particularly policies targeting rural children and adolescents.
Humans ; Child ; Adolescent ; Female ; Male ; Rural Population/statistics & numerical data* ; Overweight/epidemiology* ; Prevalence ; China/epidemiology* ; Pediatric Obesity/epidemiology* ; Obesity/epidemiology* ; Urban Population

Silent mutations within the RAS  gene have garnered increasing attention for their potential roles in tumorigenesis and therapeutic strategies. Kirsten-RAS ( KRAS ) mutations, predominantly oncogenic, are pivotal drivers in various cancers. While extensive research has elucidated the molecular mechanisms and biological consequences of active KRAS  mutations, the functional significance of silent mutations remains relatively understudied. This review synthesizes current knowledge on KRAS  silent mutations, highlighting their impact on cancer development. Silent mutations, which do not alter protein sequences but can affect RNA stability and translational efficiency, pose intriguing questions regarding their contribution to tumor biology. Understanding these mutations is crucial for comprehensively unraveling KRAS -driven oncogenesis and exploring novel therapeutic avenues. Moreover, investigations into the clinical implications of silent mutations in KRAS -mutant tumors suggest potential diagnostic and therapeutic strategies. Despite being in early stages, research on KRAS  silent mutations holds promise for uncovering novel insights that could inform personalized cancer treatments. In conclusion, this review underscores the evolving landscape of KRAS  silent mutations, advocating for further exploration to bridge fundamental biology with clinical applications in oncology.
Humans ; Mutation/genetics* ; Neoplasms/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Animals