ObjectiveTo investigate the effects of Erchentang （ECD） on the body weight of the mouse model of simple obesity induced by a high-fat diet （HFD） and decipher the underlying mechanisms. MethodsFirstly， single-cell transcriptomics （Sc-RNAseq） was employed to analyze the transcriptional changes in the ileum tissue of mice in the normal group and model group. Then， a mouse model of simple obesity was established with a high-fat diet. The successfully modeled mice were randomly allocated into the following four groups （n=8）： model， low-dose （7.5 g·kg^-1） ECD， medium-dose （15 g·kg^-1） ECD， and high-dose （30 g·kg^-1） ECD. Additionally， 8 mice of the same age were selected as the normal group. The body weight was measured at fixed time points during the 4-week gavage period. The overall efficacy of ECD in alleviating obesity was evaluated through glucose tolerance testing， behavioral analysis， hematoxylin-eosin （HE） staining， and biochemical testing. Protein docking was employed to predict the degree of binding between corresponding proteins. Molecular docking was employed to predict the binding degree between key components of ECD and target proteins. Real-time PCR was employed to determine the mRNA levels of tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， interleukin-1β （IL-1β）， CD68， CD206， zonula occludens-1 （ZO-1）， and Claudin-5 in the ileum. Immunofluorescence staining was used to observe the expression and distribution of Claudin-5 and ZO-1. ResultsThe Sc-RNAseq results indicated that the differentially expressed genes of immune cells in the model group in comparison with the normal group were primarily enriched in biological functions related to lipid metabolism and inflammatory metabolism. Additionally， these genes were associated with the janus kinases（JAK）/signal transducers and activators of transcription （STAT） signaling pathway， an inflammation-related pathway. Compared with the normal group， the model group showed increases in body weight （P<0.01） and blood glucose level （P<0.01）， a decrease in limb strength （P<0.01）， an increase in liver weight （P<0.05）， and elevated serum alanine amino-transferase （ALT） and aspartate transferase （AST） levels （P<0.05， P<0.01）. Additionally， the model group exhibited increased hepatic fat vacuoles， notably enlarged adipocytes in the epididymal and inguinal white adipose tissue， and increased inflammation. Compared with the model group， ECD groups showed reduced body weights （P<0.01） and blood glucose levels （P<0.01）， increased limb strength （P<0.05， P<0.01）， decreased liver weights （P<0.05， P<0.01）， and declined serum ALT and AST levels （P<0.05， P<0.01）. Additionally， ECD reduced hepatic fat vacuoles and the adipocyte volume in the epididymal and inguinal white adipose tissue， and alleviated inflammation. Potential interactions existed between CD68 and ZO-1/Claudin-5， as well as between CD206 and ZO-1/Claudin-5. The key components of ECD， nobiletin， diosmetin， and naringenin， all demonstrated strong binding affinity with the target proteins ZO-1 and Claudin-5. Compared with the normal group， the model group exhibited up-regulated mRNA levels of the pro-inflammatory cytokines TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and down-regulated mRNA levels of the anti-inflammatory cytokine CD206 （P<0.01） and the tight junction proteins Claudin-5 and ZO-1 （P<0.05， P<0.01）. In comparison with the model group， the ECD groups showed down-regulated mRNA levels of TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and up-regulated mRNA levels of CD206， Claudin-5， and ZO-1 （P<0.05， P<0.01）. Compared with the normal group， the model group exhibited down-regulated expression of tight junction proteins Claudin-5 and ZO-1 （P<0.01）. Compared with the model group， ECD groups showed up-regulated expression of Claudin-5 and ZO-1 （P<0.05， P<0.01）. ConclusionECD can significantly ameliorate HFD-induced obesity and excessive body weight gain in mice by improving the inflammatory microenvironment in the ileum and further restoring the integrity of the impaired ileal barrier.

Allergic conjunctivitis is a common ocular surface condition. Although corticosteroids are potent anti-inflammatory agents for its management, their use is often restricted by potential side effects. Conventional eye drops face challenges such as short retention time and poor corneal permeability, resulting in low drug bioavailability. To overcome these limitations, we developed a preservative-free synthetic high-density lipoprotein (sHDL) nanodisc eye drop containing dexamethasone palmitate. This novel formulation enhances drug stability and extends retention time on the ocular surface. In a mouse model of ovalbumin (OVA)-induced allergic conjunctivitis, the nanodisc eye drop significantly alleviated symptoms while reducing corticosteroid concentration, demonstrating excellent safety and biocompatibility. This innovative approach shows great promise for the treatment of allergic conjunctivitis and may lay the groundwork for new therapeutic strategies in anterior ocular disease management.

Nucleotide analogues (NAs) and interferon are still the first-line drugs for the treatment of chronic hepatitis B (CHB), but they still cannot completely eliminate covalently closed circular DNA (cccDNA) within hepatocytes. The clinical cure, or the disappearance of HBsAg, is the ideal goal of antiviral therapy. Although interferon therapy has a significantly greater HBsAg clearance rate and seroconversion rate than NAs, combination or sequential treatment can improve the HBsAg clearance rate and seroconversion rate to a certain extent, and only a small proportion of CHB patients can achieve clinical cure. Therefore, finding indications that predict clinical cure before and during antiviral treatment is crucial for identifying patients who are more likely to achieve HBsAg clearance at an early stage, improving clinical cure rates, and reducing treatment costs. This article reviews the research progress on predictive indicators of clinical cure of chronic hepatitis B in the past five years, explores the value of each indicator in predicting clinical cure, and provides a reference for optimizing CHB treatment strategies.

Objective:To analyze the characteristics of adverse reactions of sodium-glucose cotransporter 2 inhibitors (SGLT2i), and provide a basis for the rational clinical application.Methods:The adverse drug reaction (ADR) cases of SGLT2i reported by Beijing from January 1, 2019 to June 30, 2024 were collected through searching the National Adverse Drug Reaction Monitoring System of China. The Medical Dictionary for Regulatory Activities (MedDRA) terminology set was used to standardize the description of ADR, and the involving system organ class (SOC) and preferred term (PT) was extracted. Data of ADR were analyzed descriptively and statistically. Results:A total of 409 SGLT2i-related adverse reaction reports involving 409 patients were included. Among these patients, there were 232 females and 177 males; the median age was 62(52, 70) years, and 231 cases (56.48%) were under the age of 65 years; 5 types of SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, and henagliflozin proline) were involved, and reports of dapagliflozin was the most (279 cases, 68.22%). The primary indication for medication was diabetes (404 cases, 98.78%). The majority of ADRs did not reach the severe level (395 cases, 96.58%). The 14 cases (3.42%) of severe ADR were primarily about diabetic ketoacidosis (11 cases, 11/14), of which 7 cases presented with normal blood glucose levels and 5 cases occurred after medical stress events. The outcomes of patients were improvement in 241 cases (58.92%) and recovery in 127 cases (31.05%). In total, 476 ADR occurrences were recorded among the 409 patients, involving 82 PTs, 24 of which were not listed in the drug labels. The top 2 SOCs were the infections and infestations [26.26% (125/476)] and renal and urinary disorders [13.87% (66/476)]; the top 3 PTs were urinary tract infection [23.32% (111/476)], urinary ketone detection [6.51% (31/476)], and vulvovaginal pruritus [5.88% (28/476)]; the top 3 newly identified possible ADRs (PTs) were dizziness [2.31% (11/476)], palpitations [1.89% (9/476)], and decreased appetite [1.05% (5/476)].Conclusions:Based on the ADR monitoring data in Beijing in the past 5 and a half years, SGLT2i-associated adverse reactions primarily involved the infections and infestations, and renal and urinary disorders. ADRs identified in the study such as dizziness and palpitations are not documented in the drug labels, euglycaemic ketoacidosis accounts for a high proportion of severe reactions, and most of them occur after acute stress events.

Objective:To analyze the characteristics of adverse reactions of sodium-glucose cotransporter 2 inhibitors (SGLT2i), and provide a basis for the rational clinical application.Methods:The adverse drug reaction (ADR) cases of SGLT2i reported by Beijing from January 1, 2019 to June 30, 2024 were collected through searching the National Adverse Drug Reaction Monitoring System of China. The Medical Dictionary for Regulatory Activities (MedDRA) terminology set was used to standardize the description of ADR, and the involving system organ class (SOC) and preferred term (PT) was extracted. Data of ADR were analyzed descriptively and statistically. Results:A total of 409 SGLT2i-related adverse reaction reports involving 409 patients were included. Among these patients, there were 232 females and 177 males; the median age was 62(52, 70) years, and 231 cases (56.48%) were under the age of 65 years; 5 types of SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, and henagliflozin proline) were involved, and reports of dapagliflozin was the most (279 cases, 68.22%). The primary indication for medication was diabetes (404 cases, 98.78%). The majority of ADRs did not reach the severe level (395 cases, 96.58%). The 14 cases (3.42%) of severe ADR were primarily about diabetic ketoacidosis (11 cases, 11/14), of which 7 cases presented with normal blood glucose levels and 5 cases occurred after medical stress events. The outcomes of patients were improvement in 241 cases (58.92%) and recovery in 127 cases (31.05%). In total, 476 ADR occurrences were recorded among the 409 patients, involving 82 PTs, 24 of which were not listed in the drug labels. The top 2 SOCs were the infections and infestations [26.26% (125/476)] and renal and urinary disorders [13.87% (66/476)]; the top 3 PTs were urinary tract infection [23.32% (111/476)], urinary ketone detection [6.51% (31/476)], and vulvovaginal pruritus [5.88% (28/476)]; the top 3 newly identified possible ADRs (PTs) were dizziness [2.31% (11/476)], palpitations [1.89% (9/476)], and decreased appetite [1.05% (5/476)].Conclusions:Based on the ADR monitoring data in Beijing in the past 5 and a half years, SGLT2i-associated adverse reactions primarily involved the infections and infestations, and renal and urinary disorders. ADRs identified in the study such as dizziness and palpitations are not documented in the drug labels, euglycaemic ketoacidosis accounts for a high proportion of severe reactions, and most of them occur after acute stress events.

Nucleotide analogues (NAs) and interferon are still the first-line drugs for the treatment of chronic hepatitis B (CHB), but they still cannot completely eliminate covalently closed circular DNA (cccDNA) within hepatocytes. The clinical cure, or the disappearance of HBsAg, is the ideal goal of antiviral therapy. Although interferon therapy has a significantly greater HBsAg clearance rate and seroconversion rate than NAs, combination or sequential treatment can improve the HBsAg clearance rate and seroconversion rate to a certain extent, and only a small proportion of CHB patients can achieve clinical cure. Therefore, finding indications that predict clinical cure before and during antiviral treatment is crucial for identifying patients who are more likely to achieve HBsAg clearance at an early stage, improving clinical cure rates, and reducing treatment costs. This article reviews the research progress on predictive indicators of clinical cure of chronic hepatitis B in the past five years, explores the value of each indicator in predicting clinical cure, and provides a reference for optimizing CHB treatment strategies.

Objective:To explore the effect and safety of mesenchymal stem cell exosome microneedle introduction in the treatment of melasma.Methods:Thirty cases of female patients with stable melasma in the Department of Dermatology, Changsha Meilai Medical Beauty Hospital, aged (36±5) years and with a disease duration of (42.4±20.7) months, from July 2021 to July 2022, were retrospectively included. According to Fitzpatrick skin typing, 23 cases of type Ⅲ and 7 cases of type Ⅳ were included. All patients were locally anesthetized with lidocaine cream for 30 min, and rolled with a 0.5 mm needle in a zigzag pattern with even force, in the order of the right cheek, the left cheek, the forehead, the nose, the mandible, and the upper lip. During the rolling process, 3 ml of MSC exosome medical liquid wound dressing was applied to the facial skin, and after it was fully absorbed, exosome was locally readministered in the area of melasma. Treatment ended with a slight redness at the site of application. 1 MSC exosome wound dressing was appllied as a cold compress for 15 min after treatment. Treatment was given once every 2 weeks for 6 consecutive sessions. All the patients were followed up at 4 and 12 weeks after the last session, and the area and severity index of melasma (MASI) were scored before and after the treatment, the clinical efficiency and patient satisfaction rate and the incidence of adverse reactions were also counted.Results:At 4 and 12 weeks after the end of treatment, the skin color of all 30 patients was brighter than that before treatment, and no recurrence of melasma symptoms seen. At 12 weeks after the end of treatment, the decrease rate of MASI score was 66.1%, among which the decrease rate of MASI score in patients with type Ⅲ melasma was 63.9%, and the decrease rate of MASI score in patients with type Ⅳ melasma was 63.9%. Among the 30 patients, 1 case was cured, 25 cases showed obvious improved, 4 cases were improved, and no cases were ineffective, with an effective rate of 86.7% (26/30). Five patients were very satisfied, 18 patients were satisfied, 6 patients were generally satisfied, and 1 patient was dissatisfied; the patient satisfaction rate was 76.7% (23/30). No serious adverse reactions occurred in all patients.Conclusions:MSC exosome microneedle introduction is safe and effective in the treatment of melasma without serious adverse reactions.

Objective:To understand the residents' cognition of commercial long-term insurance in Tianjin so as to provide a reference for improving service effect and quality of long-term insurance.Methods:A total of 31 residents from six districts of Tianjin were selected for semi-structured interviews from December 2022 to February 2023 by the convenient sampling method, and the data were analyzed by Colaizzi 7-step analysis method.Results:Three themes were extracted, namely, inadequate interpretation and promotion of commercial long-term insurance, immature development of commercial long-term insurance, and the ability of commercial long-term insurance to help caregivers reduce their family burden.Conclusions:The residents of Tianjin have a low awareness of commercial long-term insurance, which cannot meet the needs of most residents. It is urgent to strengthen their publicity further and improve their system.

Objective To identify the pathogenic bacteria such as Staphylococcus aureus and Enterococcus faecalis in bloodstream infec-tions with high confidence based on three deep learning models such as GoogleNet,ResNet101,and Vgg19,compare the performance and classification ability of these models,and explore the feasibility of applying the deep learning models for the rapid identification of pathogenic bacteria in bloodstream infections.Methods The preprocessed Gram-stained bacterial images,including 1 682 images for Staphylococcus aureus and 1 723 for Enterococcus faecalis,and 688 blank control microscopic images were input into three models for training and validation,respectively.Among them,1 344 images for Staphylococcus aureus,1 376 for Enterococcus faecalis,and 544 blank control images were used for training,and the remaining images were used for validation.The model with the best performance was identified according to the classification parameters between the models.Results The ResNet101 model had the lowest cross-en-tropy loss value(0.008 710 3),the largest Epoch value(93),and the highest accuracy rate(99％)for identifying the three types of validation set images.The cross-entropy loss value,Epoch value,and accuracy rate of the GoogleNet model were 0.063 89,86 and 98.6％,respectively,for identifying the three types of validation set images.Those of the Vgg19 model were 0.035 682,86 and 97.7％,respectively.Conclusion The ResNet101 model has the best performance in the classification of three kinds of images.The deep learning model may accurately,reliably and rapidly identify the Gram-stained images of pathogenic bacteria such as Staphylococcus aureus and Enterococcus faecalis in bloodstream infections.

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.