Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

Objective To investigate the serum levels of C-C motif chemokine ligand 25(CCL25)and human Parkinson's disease protein 7(PARK7)in patients with sepsis and their relationship with acute lung injury(ALI).Methods 138 sepsis patients diagnosed and treated in Hefei Jingdongfang Hospital from February 2019 to February 2023 were selected as sepsis group.They were divided into ALI group(n=40)and non-ALI group(n=98)based on whether ALI occurred.70 healthy individuals who underwent physical examinations at the same time were taken as a control group.Enzyme linked immunosorbent assay was used to detect serum levels of CCL25 and PARK7.The correlation between serum CCL25,PARK7 and clinical indicators were analyzed by Pearson correlation analysis.Risk factors for secondary ALI in sepsis were conducted by multivariate logistic regression analysis.The value of serum CCL25 and PARK7 levels in predicting secondary ALI in sepsis were conducted by the receiver operating characteristic curve.Results Serum CCL25(367.52±46.87ng/L)and PARK7(54.26±17.45μg/L)in patients with sepsis was higher than that of the control group(48.17±5.26ng/L,12.31±4.12 μg/L),and the differences were statistically significant(t=46.825,19.813,all P＜0.05).ALI group patients CCL25(434.65±52.87ng/L vs 340.12±42.64ng/L),PARK7(103.47±22.51μg/L vs 34.18±7.46 μg/L),respiratory index(1.58±0.48 vs 0.88±0.07),PaCO2(50.11±6.27mmHg vs 40.42±5.20mmHg),APACHE Ⅱ score(23.37±3.82 point vs 17.15±3.41 point)and SOFA score(13.56±2.93 point vs 10.18±2.81 point)were all higher in the non-ALI group,while oxygenation index(237.14±23.56 point vs 341.14±21.37 point)and PaO2(55.87±8.03mmHg vs 63.11±7.14mmHg)were lower in the non-ALI group,and the differences were statistically significant(t=10.998,27.151,14.145,9.342,9.385,6.332,25.172,5.210,all P＜0.05).The serum levels of CCL25 and PARK7 in ALI patients were positively correlated with APACHE II score,SOFA score,respiratory index and PaCO2(r=0.579～0.801,all P＜0.05),while negatively correlated with oxygenation index and PaO2(r=-0.687,-0.643;-0.654,-0.712,all P＜0.05).Serum CCL25(OR=1.309,95%CI:1.040～1.646),PARK7(OR=1.288,95%CI:1.016～1.633),APACHE II score(OR=1.188,95%CI:1.019～1.384)and SOFA score(OR=1.197,95%CI:1.006～1.425)were independent risk factors for secondary ALI in sepsis patients.The area under the curve(95%CI)of the combination of serum CCL25 and PARK7 for predicting secondary ALI in sepsis was 0.833(0.784～0.872),which was greater than the individual indicators 0.770(0.725～0.835)and 0.741(0.691～0.790),and the differences were statistically significant(Z=4.602,4.318,P＜0.05).Conclusion Elevated serum levels of CCL25 and PARK7 in patients with sepsis are independent risk factors affecting the occurrence of secondary ALI in sepsis.The combination of the two has high predictive value for secondary ALI in sepsis.

Objective To observe the clinical efficacy of Yinlian Gargle in the treatment of acute radiation-induced oropharyngeal mucositis after nasopharyngeal carcinoma radiotherapy.Methods Thirty-two patients with nasopharyngeal carcinoma,who had received first radiation,were randomly split into two groups:the trial group(19 cases)and the control group(13 cases).After all groups were treated with radiotherapy and chemotherapy,the control group was given rinse treatment with saline whereas the trial group was given Yinlian Gargle.The incidence of severe acute radiation-induced oropharyngeal mucositis,the duration and intensity of oropharyngeal discomfort and pain(NRS score),quality of life(QOL-NPC score),duration and intensity of radiation-induced side effects(SE-QOL-NPC score)and symptoms of dry mouth(SE1 score)were monitored before and after intervention in two groups.Results The incidence of grade Ⅲ or above radiation-induced oropharyngeal mucositis until the sixth week of radiotherapy in the trial group was considerably lower than that in the control group(P＜0.001),while the incidence of grade I or above radiation-induced oropharyngeal mucositis at 1 month after radiotherapy in the trial group was obviously lower than that in the control group(P＜0.001).The NRS score of pharyngeal discomfort of the trial group was lower than that of the control group starting from the second week of radiotherapy(P＜0.05).The NRS score of oral and oropharyngeal pain was lower than that of the control group starting from the fourth week of radiotherapy(P＜0.05).The SE1 score of the trial group was higher than that of the control group starting from the fifth week of radiotherapy(P＜0.05).After one month of the completion of the radiotherapy,the NRS score of pharyngeal discomfort and the NRS score of oral and oropharyngeal pain in the trial group were lower than those of the control group(P＜0.001).The QOL-NPC score,SE-QOL-NPC score,and SE1 score were all higher than those in the control group(P = 0.05 or P＜0.05).Conclusion Patients with nasopharyngeal cancer can greatly reduce their risk of developing severe acute radiation-induced oropharyngeal mucositis,effectively delay and relieve related symptoms,and enhance quality of life by consistently using Yinlian Gargle during radiotherapy.Additionally,a month after the completion of radiotherapy,it still has positive therapeutic effects on acute radiation-induced oropharyngeal mucositis.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Curettage is the main treatment method for oral maxillofacial cystic lesions,but simple curettage may easily damage surrounding structures such as adjacent teeth and nerves,leading to incomplete removal of the cyst and large jaw defects.The curettage assisted by endoscopy can provide a good surgical field for the surgeons,can clearly identify the important anatomical structure during the operation and can remove the cyst wall tissue as much as possible,thereby reducing the damage and reducing the recurrence rate of the lesion.This article combines the characteristics of maxillofacial surgery with clinical treatment experience,summarizes relevant literature from both domestic and international sources,and engages in discussions with experts in order to provide reference for the clinical treatment of jaw cystic lesions with endo-scope assisted curettage.

Objective lo contrast the diagnostic efficacies of perineal and transrectal approaches for combined prostate biopsies guided via magnetic resonance imaging(MRI)and ultrasound fusion imaging.Method A retrospective analysis of clinical data from 271 patients subjected to combined prostate biopsies guided by MRI and ultrasound fusion imaging at the first people's hospital of Wuxue city and Wuhan Tongji Hospital from January 2022 to November 2023 was conducted.They were divided into two groups according to the puncture path,132 cases were transrectal and 139 cases were perineal.The differences between the detection rates of prostate cancer(PCa)and clinical significant prostate cancer(csPCa)across different prostate imaging reporting and data system(PI-RADS)scores and lesion localizations within the two puncture paths were compared.Results The detection rates of PCa in the perineal and transrectal puncture groups(68.3％vs.59.8％,P=0.145)and csPCa(64.7％vs.55.3％,P=0.112)did not exhibit statistically significant differences.However,the perineal puncture group experienced fewer complications.For patients with a PI-RADS score of 4,both PCa(77.2％vs.56.1％,P=0.027)and csPCa(71.9％vs.48.8％,P=0.02)detection rates were higher via the perineal combined biopsy),compared to the transrectal path.Additionally,for apical(PCa:84.3％vs.48.7％,P=0.001;csPCa:81.8％vs.48.7％,P=0.004)and anterior(PCa:77.1％vs.46.5％,P=0.006;csPCa:68.6％vs.44.2％,P=0.031)prostate lesions,the detection rates via the perineal combined biopsy were considerably higher than those of the transrectal path.Conclusion For patients carrying a PI-RADS score of 4 or with prostate lesions situated at the apical or anterior section,the perineal approach for biopsy sampling emerges as the most appropriate method.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

In recent years,China has made great progress in basic nanomedicine,nanotoxicology and nanobiology research.Nanotechnology has been continuously applied in biomaterial and medical device,more and more medical devices applying nanomaterials are developed and manufactured.In order to gain more comprehension and accurate understanding of the research and industrial development in nanobiomaterial medical devices,this study reviewed the common nanomaterial in medical devices and the regulatory situation of nanomaterial medical devices at home and abroad,and discussed the current challenges in biological evaluation of nanomaterial medical devices,with a view to providing ideas for the safety evaluation and research of related products.

Objective To investigate the infectivity of hepatitis A virus(HAV)cell-adapted strain in a type Ⅰ interferon receptor-deficient mouse model.Methods The biological charateristics of HM175/18f were identified,including the viral protein expression and viral proliferation by indirect immunofluorescence,Western blot and real-time quantitative RT-PCR in vitro.Then,type Ⅰ interferon receptor-deficient A129 mice were infected with HM175/18f via intravenous injection.The viral RNA load in serum,feces and liver tissues of infected mice were detected to determine the replication of HAV in vivo.The level of serum alanine aminotransferase(ALT)and HE staining of liver tissues were used to evaluate liver injury.Additionally,the dynamic changes of HAV-specific IgG antibody was detected to assess the humoral immune response induced by HM175/18f.Results A129 mice infected with HM175/18f did not show obvious clinical symptoms,nor was the ALT level significantly elevated.However,viral RNA persisted in the liver tissue of infected mice until 42 days after infection.There was focal infiltration of lymphocytes and neutrophils in the liver tissue of infected mice,but no focal necrosis was observed.More importantly,HM175/18f infection caused significant viremia and sustained fecal virus shedding.In addition,HM175/18f induced a significant HAV-specific humoral immune response in A129 mice.Conclusion Our study has revealed the infectivity of HAV cell-adapted strain HM175/18f in type Ⅰ interferon receptor-deficient mice,and identified the attenuated characteristics of HM175/18f,which not only contributes to our understanding of the pathogenesis of HAV,but also expand the applications of a type Ⅰ interferon receptor-deficient mouse model in the study of hepatitis A.

Objective:To evaluate the clinical and prognostic differences in acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) children under different diagnostic criteria (World Health Organization (WHO) 2016 and WHO 2022 criteria).Methods:In this retrospective cohort study, clinical characteristics and prognosis information of 260 acute myeloid leukemia (AML) children admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2017 to August 2021 were analyzed retrospectively. According to WHO 2016 and WHO 2022 diagnostic criteria, patients were divided into AML-MRC group and non-AML-MRC group, the prognostic and genetic differences between two groups were compared respectively. Meanwhile, the characteristics of children with 8 MRC-related genes defined in WHO 2022 diagnostic criteria were described. Mann-Whitney U test, chi-square test were used for comparison between groups. Survival curve was plotted by Kaplan-Meier method, and comparison between groups was performed by Log-Rank method. Results:Among the 260 children, there were 148 males and 112 females. The follow-up time was 26 (16, 38) months. A total of 28 children (10.8%) were diagnosed with AML-MRC according to the WHO 2016 diagnostic criteria. Compared with non-AML-MRC children, the frequency of PTPN11, RUNX11, SH2B3, MPL and STAG2 mutations was higher in AML-MRC children (25.0% (7/28) vs. 4.3% (10/232), 14.3% (4/28) vs. 3.9% (9/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 0.9% (2/232), all P<0.05). The 2-year overall survival (OS) and events free survival (EFS) rate of 28 AML-MRC children under WHO 2016 diagnostic criteria were worse than those of 232 non-AML-MRC children ((62.1±10.8)% vs. (94.5±1.6)%, χ2=22.1 ,P<0.001;(48.0±10.6)% vs. (70.9±3.2)%, χ2=6.33, P=0.012). Twenty-seven children (10.4%) were eventually diagnosed with AML-MRC according to WHO 2022 criteria, their 2-year OS rate were worse than 233 non-AML-MRC children ((60.8±11.1)% vs. (94.5±1.6)%, χ2=24.49 ,P<0.001), and there was no statistically significant difference in EFS rate between two groups at 2 years ((55.1±10.8)% vs. (70.1±3.2)%, χ2=2.44 , P=0.119). Conclusions:Compared with the 2022 WHO diagnostic criteria, the survival rates of children with AML-MRC under the 2016 WHO diagnostic criteria were worse than that of children without MRC.The new version of the AML-MRC diagnostic criteria emphasizes the importance of genes.