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.

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.

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.

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.

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:To understand the current antiviral treatment status and various clinical types of treatment plans in Xiamen City so as to explore ways to improve and optimize the diagnosis and treatment standards for chronic hepatitis B.Methods:A cross-sectional survey method was used to study the antiviral treatment status and treatment plans for chronic hepatitis B patients who visited and were diagnosed in the Department of Infectious Diseases and Hepatology of all tertiary hospitals in Xiamen City at 0:00~23:59 on May 25, 2022.Results:A total of 665 cases were surveyed in this study, with an antiviral treatment rate of 81.2%(540/665). The antiviral treatment rate of patients who accorded with the current guidelines for antiviral treatment indications was 85.8%(507/591). The antiviral treatment rate for 362 outpatients was 72.9%(264/362). Among them, the antiviral treatment rates were 80.1%, 89.3%, and 25.0%(226/282, 25/28, 13/52), respectively, for patients diagnosed with chronic hepatitis B, hepatitis B cirrhosis, and hepatitis B surface antigen-carrying status. The treatment plan for all outpatient patients was mainly oral nucleos(t)ide analogues, accounting for 59.1%(214/362). The antiviral treatment rate for 303 inpatients was 91.1%(276/303). The various clinical types of antiviral therapy rates among all patients were 70%~95%. The antiviral treatment plan for inpatients was mainly based on pegylated interferon alpha treatment, accounting for 72.6%(220/303).Conclusion:Antiviral treatment for chronic hepatitis B in Xiamen City can still be strengthened to meet the current demand for expanding antiviral treatment indications. Antiviral treatment rates and various types of treatment plans differ between outpatients and inpatients; thus, further awareness and acceptance of the goal of improving antiviral therapy, especially in outpatients, and the possibility for a clinical cure based on pegylated interferon alpha treatment are needed to maximize the benefit to more patients.

Objective:To determine the correlation between the radiologic magnetic resonance imaging(MRI)depth of invasion(MRI-DOI)and pathologic depth of invasion(p-DOI)in oral cavity primary tongue squamous cell carcinoma(TSCC).Methods:Fifty-two cases of patho-logically proven primary TSCC were selected from patients admitted to The Ninth People's Hospital Affiliated to Shanghai Jiao Tong Uni-versity School of Medicine between January 2015 and December 2018.The p-DOI was measured,and the relationship between p-DOI and patients'clinicopathological parameters and prognosis were analyzed.The MRI-DOI was retrospectively measured,and the correlation between MRI-DOI and p-DOI was investigated.Results:Among the 52 patients,the average p-DOI was(8.5±5.5)(1-30)mm.p-DOI was signi-ficantly correlated with tumor size(P=0.021)and tumor site(P=0.047)when p-DOI was>5 mm,and significantly correlated with level Ⅲ lymph node metastasis(P=0.01)when p-DOI was≥10 mm.A close relationship between p-DOI>7 mm and the patient 5-year survival was also demonstrated(P=0.048).The average MRI-DOI was(10.3±4.3)mm,with a maximum of 19.9 mm and a minimum of 3.1 mm.The MRI-DOI≥10 mm also predicted poor survival in patients with TSCC(P=0.043).The MRI-DOI measured was generally slightly higher than p-DOI,with an average difference of 1.94 mm,and a strong correlation was found between MRI-DOI and p-DOI(r=0.831,P<0.001).Conclusions:MRI-based radiologic DOI measurement was useful in estimating postoperative p-DOI,and may help predict the depth of invasion of tumors preoperatively,which has important reference value for treating primary TSCC.

Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.

Objective To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children.Methods A retrospective analysis was performed on 23 chil-dren with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation(arthrography with elastic nail group)from January 2019 to December 2022,including 12 males and 11 fe-males,aged from 2 to 12 years old with an average of(7.36±1.89)years old;According to Judet fracture types,14 children were type Ⅲ and 9 children were type Ⅳ.In addition,23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation(elastic nail group),including 11 males and 12 females,aged from 2 to 14 years old with an average of(7.50±1.91)years old;Judet classi-fication included 15 children were type Ⅲ and 8 children were type Ⅳ.Operative time and intraoperative fluoroscopy times were compared between two groups.Metaizeau evaluation criteria was used to evaluate fracture reduction,and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups.Results Both groups were followed up for 12 to 24 months with an average of(16.56±6.34)months.Operative time and intraoperative fluoroscopy times of elastic nail group were(56.64±19.27)min and(21.13±7.87)times,while those of joint angiography with elastic nail group were(40.33±1 1.50)min and(12.10±3.52)times;there were difference between two groups(P＜0.05).According to Metaizeau evaluation,11 patients got excellent result,9 good and 3 fair in joint angiography with elastic nail group,while in elastic nail group,5 ex-cellent,13 good,4 acceptable,and 1 poor;the difference between two groups was statistically significant(P＜0.05).According to Tibone-Stoltz criteria,14 patients got excellent result,8 good,and 1 fair in joint arthrography with elastic nail group;while in elastic nail group,12 patients got excellent result,9 good,1 fair and 1 poor;there was no significant difference between two groups(P＞0.05).Conclusion Compared to percutaneous elastic intramedullary nail fixation,closed reduction assisted by arthrography has advantages of reduced operation time,decreased intraoperative fluoroscopy frequency,and improved fracture reduction.Arthrography enables clear visualization of the anatomical structures of radius,head,neck,bone,and cartilage in children,facilitating comprehensive display of fracture reduction and brachioradial joint alignment.This technique more pre-cisely guides the depth of elastic intramedullary nail implantation in radius neck,thereby enhancing surgical efficiency and success rate.