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 influencing factors of incident caries at age 5 among caries-free 3-year-old children in Beijing, construct a machine learning prediction model based on oral health behavioral data, and provide a scientific basis and practical tool for early risk identification, stratified prevention and control, and home-kindergarten-medical collaborative intervention of incident dental caries in preschool children. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and written informed consent was obtained from the guardians of the study participants and their guardians. Children with complete baseline data at age 3 and follow-up data at age 5 from Beijing public oral health programs were included. Oral examinations were conducted according to World Health Organization diagnostic criteria, and questionnaires were completed by guardians. Risk factors were screened by Logistic regression. The total sample was randomly divided into a test set (20%) and a validation set (80%). Five-fold cross-validation was performed on the validation set for model training and tuning, and the final model performance was evaluated on the test set. Four machine learning models—decision tree, random forest, Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM)—were constructed. Model performance was evaluated using the area under the curve (AUC), accuracy, and specificity. Shapley Additive Explanations (SHAP) was used for model interpretation. Results: The incidence of incident caries for 3 372 5-year-old children in Beijing was 50.96%. Multivariate logistic regression showed that parental caries, sleeping with milk, frequent feeding at night, no postprandial cleaning, high sugar intake, insufficient bedtime tooth brushing, and non-fluoride toothpaste use were significant risk factors (P < 0.05). Although all four machine learning models performed well, the XGBoost model performed the best (AUC = 0.806). Feature importance and SHAP analysis indicated that the frequency of bedtime tooth brushing, the frequency of candy consumption, and parental caries status were the top three predictors. Conclusion The XGBoost model based on oral health behaviors at age 3 can accurately predict the risk of incident caries in 5-year-old children in Beijing. Bedtime tooth brushing, sugar control, and parental oral health management are key points for caries prevention in preschool children.

Background Amid global climate change, extreme environmental events are occurring more frequently, and it is imperative to investigate the impacts of combined exposure to fine particluate matter (PM_2.5) and cold spells (CS) on population mortality. Objective To analyze the association between sequential extreme PM_2.5-cold spell (EP-CS) events and non-accidental mortality among residents in Zigong City from 2016 to 2021. Methods Using time-series study design, meteorological data in Zigong were collected from the Zigong Meteorological Bureau for the period from January 1, 2016 to December 31, 2021, while daily non-accidental mortality data were obtained from the mortality surveillance system of the Zigong Center for Disease Control and Prevention. We adopted the percentile method to define extreme PM_2.5 events and cold spells. We analyzed the risk effect of EP-CS events on non-accidental mortality among residents in this city and explored the potential amplification of damage resulting from different patterns of consecutive extreme events by using distributed lag nonlinear model (DLNM). We also conducted stratified analyses based on age, gender, education level, and marital status. Results The EP-CS events demonstrated a significant impact on non-accidental mortality among the local residents, exhibiting a certain lagged effect. The effects on the overall residents lasted from lag0 (RR=1.030, 95%CI: 1.013, 1.048) to lag14 (RR=1.035, 95%CI: 1.019, 1.052). Notably, the effects were more pronounced among females, individuals aged 65 years and above, and those who were never married, divorced, or widowed. Different patterns of EP-CS events all associated with adverse effects, the health impact of EP-CS events was significantly greater than that of individual PM_2.5 pollution or CS events. The analysis of lag effects across different event patterns revealed that the overall effect of EP-CS events with shorter intervals (0–7 d) had a stronger effect compared to EP-CS with longer intervals (8–14 d), and the RR values of lag14 were 1.034 (95%CI: 1.015, 1.054) and 1.017 (95%CI: 1.007, 1.027), suggesting that the damaging effect of compound events occurring in the short term was more significant. Conclusion All sequential extreme EP-CS events have an impact on non-accidental mortality among residents in this city, with compound events demonstrating a stronger effect. Females, individuals aged ≥65 years, and those who were never married, divorced, or widowed are more sensitive to EP-CS events.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective:To investigate the efficacy and safety of transurethral incision for the treatment of ureterocele in infants.Methods:A retrospective analysis of 28 cases of ureterocele admitted from March 2012 to May 2023 were reviewed, all of which were less than 1 year old, 16 male and 12 female, with an average age of(5.7±3.5)months. The ureterocele was located on the left side in 8 cases, on the right side in 15 cases, and bilaterally in 5 cases. There were 12 cases of single system ureterocele, of which 7 cases were unilateral and 5 cases were bilateral. Duplex system ureterocele was observed in 16 cases, all of which were unilateral. Clinical manifestations: urinary tract infection in 13 cases, 11 cases of ureterocele or hydronephrosis and ureteral dilation were found during antenatal examination, and 4 cases of ureterocele were found after birth. Urological ultrasound, intravenous pyelography(IVP) and voiding cystourethrography(VCUG) were performed in all children, and 17 cases underwent magnetic resonance urolography (MRU), and confirm the diagnosis of ureterocele preoperatively. All of the cases were performed the transurethral incision.The ureterocele was punctured and incised 1-2 mm at the base of the bulge, and 2-4 points were punctured according to the bulge atrophy. Bilateral ureteroceles were punctured and incised simultaneously. Postoperative urine routine test, urinary tract color ultrasound and VCUG were performed to determine if there is urinary tract infection, hydronephrosis, ureteral dilation and bulging, and whether a second surgery is needed.Results:All operations were conducted successfully. The intraoperative bleeding was less than 3 ml and no intraoperative complications. The operative time was (28.4±10.3) min. The median postoperative follow-up was 34 (32, 36) months. Six cases underwent postoperative VCUG examination. Eleven children were recovered well with single systemic ureterocele. One child developed grade Ⅳ vesicoureteral reflux(VUR)and combined with bladder diverticulum, and ureterocele underwent open diverticulotomy and ureteral reimplantation six months after surgery. Nine children were recovered well with duplex systemic ureterocele. Six cases of children developed infection, of which 2 cases had an infection once within one month after TUI, and the other four cases still had intermittent infections after six months and VCUG was performed, and one case showed grade Ⅲ VUR of the lower ureter, which was observed conservatively, while the other three cases had enlarged cysts but no VUR, and upper heminephrectomy was performed, and the patients recovered well after surgery. Except for these 6 exceptions, in another case, after ten years of follow-up, the ureterocele became larger but no VUR, and the results were good after a second transurethral incision. There was no significant difference in the postoperative infections, new VUR cases, and secondary surgeries between the two groups.Conclusions:Transurethral incision has good surgical effect on children with single system ureterocele and duplex system ureterocele, and has advantages of easy operation, less trauma, safety and effectiveness, and few complications. It deserves to be recommended as the treatment of choice, especially for infants and young children.

This study analyzed the epidemiological characteristics and trends of respiratory syncytial virus (RSV) infections among inpatients with acute respiratory infections (ARI) in a children′s hospital in Shenzhen City inpatients from 2020 to 2023. From January 2020 to December 2023, multiple reverse transcription polymerase chain reaction (RT-PCR) combined with capillary electrophoresis fragment analysis technology was used to detect the nucleic acids of 12 respiratory pathogens, including RSV, in hospitalized children diagnosed with ARI. The patients were divided into six age groups: 0 to <6 months, 6 months to <1 year, 1 to <2 years, 2 to <5 years, 5 to <10 years, and 10 to <18 years. A total of 53 033 children were tested, including 6 830 RSV positive cases, with an overall positivity rate of 12.88%. The annual RSV positivity rates from 2020 to 2023 were 20.04%, 16.18%, 4.89%, and 13.33%, respectively, with statistically significant differences between the years ( χ2=1 185.994, P<0.001). The positive rate of RSV detection decreased with increasing age across all years (all P trend<0.05). From 2020 to 2023, the proportion of RSV-positive cases aged 2 to 5 years and older showed an increasing trend ( P trend<0.001 for all years). Compared to 2023, the median age of RSV-infected children was lower in 2020 ( Z=7.826, P<0.001) and 2021 ( Z=6.106, P<0.001). The proportion of severe infections requiring ICU admission did not change significantly across all years ( χ2=0.179, P=0.981). The RSV epidemic season in 2020 mainly occurred during 28-43 weeks, and in 2021, it spanned from 22-43 weeks. However, in 2022, the season was delayed until the 49th week and lasted for three weeks. In 2023, the seasonal epidemic appeared earlier, starting in the 14th week and lasting for 28 weeks. From 2020 to 2023, the rate of RSV co-infections with other pathogens (mycoplasma pneumoniae, human parainfluenza virus, human bocavirus, human coronavirus, human metapneumovirus, and influenza A) significantly increased (all P trend<0.01). In conclusion, the epidemiological characteristics of RSV infections in Shenzhen Children′s Hospital changed from 2020 to 2023. In 2022, there were only delayed, low-intensity and short-lived seasonal epidemics. However, in 2023, there was an earlier and prolonged epidemic, with increased infections in children aged 2 to 5 years and older and a rise in co-infections, while the proportion of severe infections requiring ICU admission remained unchanged.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To explore the expression level of Porphyromonas gingivalis, downstream of tyrosine kinase 3 (DOK3) and tumor-associated macrophage (TAM) in the tumor immunomicroenvironment of oral squamous cell carcinoma (OSCC) and the correlation with clinicopathological characteristics and prognosis of patients.Methods:A retrospective case-control study was conducted. The clinical data of 200 OSCC patients with Porphyromonas gingivalis-positive confirmed by 16S rDNA sequencing technology in the First Affiliated Hospital, Xinjiang Medical University between June 2008 and June 2020 were collected. The tumor tissues and the corresponding adjacent normal mucosal tissues of 6 OSCC patients (including 3 cases with Porphyromonas gingivalis -positive and 3 cases with Porphyromonas gingivalis-negative) were selected for high-throughput sequencing to screen differentially co-expressed genes. Immunohistochemistry method was used to detect the expressions of Porphyromonas gingivalis, DOK3, and CD206 (a TAM marker). The median H score of OSCC tissues was used as the threshold to categorize the expression level of Porphyromonas gingivalis, DOK3 and CD206 into low-expression (H score < threshold) and high-expression (H score ≥ threshold) groups. The overall survival (OS) analysis was conducted by using the Kaplan-Meier method, and the log-rank test was employed.Results:The high-throughput sequencing results revealed that DOK3 is a differentially co-expressed gene among normal oral mucosa, Porphyromonas gingivalis-positive, and Porphyromonas gingivalis-negative OSCC. In 200 patients with Porphyromonas gingivalis-positive OSCC, 139 exhibited high expression of Porphyromonas gingivalis (H score ≥ 7 points), while 61 showed low expression (H score < 7 points). There were statistically significant differences in the expression levels of Porphyromonas gingivalis in patients with different survival status, pathological T stage, pathological N stage, clinical stage, tumor diameter, degree of tumor differentiation and recurrence (all P < 0.05). Among the 139 OSCC patients with high expression of Porphyromonas gingivalis, 92 cases showed high expression of DOK3 (H score ≥ 6 points) and 47 showed low expression (H score < 6 points); 78 cases exhibited high expression of CD206 (H score ≥ 6 points), while 61 showed low expression (H score < 6 points). There were statistically significant differences in the DOK3 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different age, survival status, pathological T stage, pathological N stage, and recurrence (all P < 0.05). There were statistically significant differences in the CD206 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different pathological T stage, clinical stage, and degree of tumor differentiation (all P < 0.05). The expression of Porphyromonas gingivalis was positively correlated with the expressions of DOK3 and CD206 (both P < 0.01). At the last follow-up on April 6th, 2024, the median follow-up time was 45 months (3 to 106 month range). The median OS time of the 200 patients was 2 429 d, and the 3-year OS rate was 63.9%. The OS of OSCC patients with high expressions of Porphyromonas gingivalis, DOK3, and CD206 was worse than that in those with low expressions (all P < 0.05). Conclusions:The high expression levels of Porphyromonas gingivalis, DOK3, and TAM are associated with a poor prognosis of OSCC patients, suggesting their potential as key biomarkers for prognostic evaluation.