Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

AIM To establish an HPLC method for the simultaneous content determination of 5-hydroxymethylfurfural,chlorogenic acid,caffeic acid,strychnine,paeoniflorin,ferulic acid,paeoniflorin Ⅰ,epimedium glycoside,psoralen,isopsoralen and glycyrrhetinic acid in Bunao Soft Capsules.METHODS The analysis was performed on a 35 ℃ thermostatic Waters Symmetry C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.RESULTS Eleven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.47％-103.30％with RSDs of 1.13％-2.80％.CONCLUSION This simple and reliable method can be used for the quality control of Bunao Soft Capsules.

Chronic obstructive pulmonary disease (COPD) poses a significant public health challenge in China due to its high prevalence and substantial disease burden. Primary healthcare institutions (PHIs) serve as the cornerstone for COPD prevention and management. However, they currently face critical challenges, including inadequate diagnostic capacity, suboptimal treatment standardization, and limited patient awareness. In recent years, national efforts have initiated the development of a primary-level COPD prevention and management network. Key strategies include incorporating COPD into the Fundamental Public Health Service Program (FPHSP), strengthening lung function screening, promoting tiered diagnosis and treatment systems, establishing central-local coordination mechanisms, and implementing National Major Public Health Service Programs. Future directions necessitate focused efforts on: constructing integrated prevention and treatment models; optimizing the two-way referral system; enhancing screening for high-risk populations; leveraging digital health empowerment; and establishing a multi-dimensional quality evaluation system. These concerted actions are essential to build a comprehensive, high-quality COPD healthcare management system within primary care settings, ultimately contributing to the goals of the Healthy China Initiative (2019-2030).

Objective:To explore the differences in bacterial communities within tissues during the process of oral mucosal carcinogenesis, and analyze the relationship between the high-abundance species Prevotella intermedia (Pi) and the occurrence and development of oral mucosal carcinogenesis. Methods:Fresh tissue samples were collected from patients diagnosed with oral leukoplakia (OLK), oral squamous cell carcinoma (OSCC), and healthy controls (HC) at Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, from January 2022 to November 2024, following strict inclusion criteria. Bacterial DNA was extracted from these specimens, and the 2bRAD sequencing for microbiome (2bRAD-M) was employed to analyze and compare the α and β diversity, as well as the community composition of bacteria within tissues, aiming to identify specifically expressed bacteria. Subsequently, paraffin-embedded clinical specimens were collected: 15 cases in the OLK group (including 4 cases of simple hyperplasia, 6 cases of mild dysplasia, and 5 cases of moderate to severe dysplasia), 12 cases in the OSCC group, and 5 cases in the HC group. A 4-nitroquinoline N-oxide (4NQO)-induced OLK progression mouse model was also constructed. Mice were randomly divided into three groups using a random number table, with six in each group. The negative control group was given distilled water to drink; Group 1 was given distilled water containing 4NQO to drink until week 12, while Group 2 was given distilled water containing 4NQO to drink until week 22. After the mice were sacrificed, their tongue tissue were collected and fixed. Fluorescence in situ hybridization (FISH) with specific probes was used to validate the presence of Pi in human and mouse tissue sections, analyzing the correlation between histopathological grading and the invasion depth of Pi.Results:The 2bRAD-M microbial analysis revealed that the relative abundance of Pi in OSCC tissues (10.80%) was significantly higher than in the HC group (0.50%) ( P=0.001) and OLK group (0.70%) ( P=0.002). FISH probe detection showed that the fluorescence intensity of Pi in human OSCC tissues [123.50 (101.00, 142.30)] was higher than in the HC group [0.00 (0.00, 28.50)], simple hyperplasia OLK [0.00 (0.00, 35.25)], and mild dysplasia OLK [24.50 (0.00, 55.50)] groups, with statistically significant differences respectively ( P=0.002, P=0.003, P=0.005). However, there was no significant difference compared to moderate to severe dysplasia OLK [56.00 (28.00, 62.50)] ( P=0.210). The fluorescence area of Pi in human OSCC tissues [8 615.00 (7 439.00, 11 084.00)] was significantly larger than in the HC group [0.00 (0. 00, 45.00)], simple hyperplasia OLK group [0.00 (0.00, 81.00)], mild dysplasia [49.00 (0.00, 151.00)], and moderate to severe dysplasia groups [1 450.00 (454.00, 2 892.00)], with highly significant differences ( P<0.001). There was a significant correlation between the invasive depth of Pi and the degree of histopathological grading ( P<0.001). In mice, the fluorescence intensity of Pi in OSCC tissues [120.00 (110.00, 127.00)] was significantly higher than in the HC group [0.00 (0.00, 12.25)] ( P<0.01), but showed no significant difference compared with the OLK group [50.00 (0.00, 58.00)] ( P>0.05). The fluorescence area of Pi in mice OSCC tissues [11 020.00 (6 790.00, 12 102.00)] was significantly larger than in the HC group [0.00 (0.00, 56.75)] and the OLK group [0.00 (0.00, 751.50)] ( P=0.006, P=0.043). There is a significant correlation between the depth of invasion of Pi and the degree of histopathological grading ( P<0.01). Conclusions:This study suggests that Pi in oral mucosal tissue may be a potential biomarker for early detection of OSCC and play an important role in the carcinogenesis process of oral mucosa.

Objective To conduct a quantitative risk assessment of Listeria monocytogenes(LM)in prepackaged,non-vacuum sealed,short shelf-life,ready-to-eat meat products in Chengdu using the@Risk software.Methods Based on monitoring data of LM contamination in pre-packaged,non-vacuum sealed,refrigerated ready-to-eat meat products in Chengdu obtained from a previous study,a risk assessment model was established.The risk of LM infection caused by consuming cooked meat products in different groups of people was quantitatively assessed.In addition,the growth of LM in cooked meat products,from retail to consumption,was also taken into consideration in the assessment.Results In Chengdu,the numbers of potential cases of listeriosis caused by consumption of prepackaged,non-vacuum sealed,refrigerated ready-to-eat meat products were 0.01(95％confidence interval[CI]:0-1.71 × 10-2)per year per million in healthy individuals aged 5-＜65 years old,0.22(95％CI:0-2.67 × 10-1)in healthy individuals aged 65 and above,and 2.88(95％CI:3.85 × 10-8-4.35)in pregnant women.According to the results of the sensitivity analysis,the initial pollution level of LM in the retail stage was the most important factor affecting the prevalence(R=0.25),followed by retail temperature(R=0.08),retail time(R=0.07),and amount of consumption per meal(R=0.07).Conclusions For pre-packaged,non-vacuum sealed,cooked meat products,the most important measure to reduce the prevalence of listeriosis is to control the initial contamination level,which requires food processing plants to regularly clean and strictly disinfect the processing environment and equipment to minimize LM contamination at the source.Retail delicatessens should strictly maintain a storage temperature below 5.0℃ and strictly adhere to product shelf-life recommendations.As for consumers,they should consume these meat products as soon as possible after purchase or store them under refrigerated conditions and shorten the storage time.Pregnant women should thoroughly heat the meat products before eating to reduce the risk of listeriosis.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Objective:To explore the differences in bacterial communities within tissues during the process of oral mucosal carcinogenesis, and analyze the relationship between the high-abundance species Prevotella intermedia (Pi) and the occurrence and development of oral mucosal carcinogenesis. Methods:Fresh tissue samples were collected from patients diagnosed with oral leukoplakia (OLK), oral squamous cell carcinoma (OSCC), and healthy controls (HC) at Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, from January 2022 to November 2024, following strict inclusion criteria. Bacterial DNA was extracted from these specimens, and the 2bRAD sequencing for microbiome (2bRAD-M) was employed to analyze and compare the α and β diversity, as well as the community composition of bacteria within tissues, aiming to identify specifically expressed bacteria. Subsequently, paraffin-embedded clinical specimens were collected: 15 cases in the OLK group (including 4 cases of simple hyperplasia, 6 cases of mild dysplasia, and 5 cases of moderate to severe dysplasia), 12 cases in the OSCC group, and 5 cases in the HC group. A 4-nitroquinoline N-oxide (4NQO)-induced OLK progression mouse model was also constructed. Mice were randomly divided into three groups using a random number table, with six in each group. The negative control group was given distilled water to drink; Group 1 was given distilled water containing 4NQO to drink until week 12, while Group 2 was given distilled water containing 4NQO to drink until week 22. After the mice were sacrificed, their tongue tissue were collected and fixed. Fluorescence in situ hybridization (FISH) with specific probes was used to validate the presence of Pi in human and mouse tissue sections, analyzing the correlation between histopathological grading and the invasion depth of Pi.Results:The 2bRAD-M microbial analysis revealed that the relative abundance of Pi in OSCC tissues (10.80%) was significantly higher than in the HC group (0.50%) ( P=0.001) and OLK group (0.70%) ( P=0.002). FISH probe detection showed that the fluorescence intensity of Pi in human OSCC tissues [123.50 (101.00, 142.30)] was higher than in the HC group [0.00 (0.00, 28.50)], simple hyperplasia OLK [0.00 (0.00, 35.25)], and mild dysplasia OLK [24.50 (0.00, 55.50)] groups, with statistically significant differences respectively ( P=0.002, P=0.003, P=0.005). However, there was no significant difference compared to moderate to severe dysplasia OLK [56.00 (28.00, 62.50)] ( P=0.210). The fluorescence area of Pi in human OSCC tissues [8 615.00 (7 439.00, 11 084.00)] was significantly larger than in the HC group [0.00 (0. 00, 45.00)], simple hyperplasia OLK group [0.00 (0.00, 81.00)], mild dysplasia [49.00 (0.00, 151.00)], and moderate to severe dysplasia groups [1 450.00 (454.00, 2 892.00)], with highly significant differences ( P<0.001). There was a significant correlation between the invasive depth of Pi and the degree of histopathological grading ( P<0.001). In mice, the fluorescence intensity of Pi in OSCC tissues [120.00 (110.00, 127.00)] was significantly higher than in the HC group [0.00 (0.00, 12.25)] ( P<0.01), but showed no significant difference compared with the OLK group [50.00 (0.00, 58.00)] ( P>0.05). The fluorescence area of Pi in mice OSCC tissues [11 020.00 (6 790.00, 12 102.00)] was significantly larger than in the HC group [0.00 (0.00, 56.75)] and the OLK group [0.00 (0.00, 751.50)] ( P=0.006, P=0.043). There is a significant correlation between the depth of invasion of Pi and the degree of histopathological grading ( P<0.01). Conclusions:This study suggests that Pi in oral mucosal tissue may be a potential biomarker for early detection of OSCC and play an important role in the carcinogenesis process of oral mucosa.

Objective:To evaluate the efficacy of multimodal prehabilitation in patients with refractory functional constipation undergoing Jinling procedure(modified Duhamel surgery).Methods:In this prospective randomized controlled trial,80 patients with refractory functional constipation scheduled for Jinling procedure at the Department of General Surgery,the General Hospital of Eastern Theater Command between January 2020 and December 2021 were enrolled.Participants were randomly assigned to either the observation group(n=40,multimodal prehabilitation)or control group(n=40,routine nursing care).Outcome measures included:time to first flatus,time to first ambulation,defecation volume on postoperative day 5,length of hospitalization,nutritional markers(hemoglobin,albumin,total protein at postoperative day 7),anxiety/depression scores(Hospital Anxiety and Depression Scale,HADS),and total complication rates.Results:Compared to controls,the first ventilation time(48.02±6.15)h,first ambulation time(49.92±5.58)h,defecation volume on the fifth day(234.50±51.03)mL,hospital stay(13.15±2.64)d,anxiety score(43.68±3.45)points,depression score(43.81±1.58)points,and the total incidence of postoperative complications(15%)were significantly lower in the observation group(all p values<0.05).By contrast,the serum levels of hemoglobin(115.60±11.60)g/l,albumin(41.19±5.79)g/L and total protein(61.64±4.94)g/L on day 7 post-operatively were significantly higher in the observation group than those in the control group(P<0.05).Conclusions:Multimodal prehabilitation enhances postoperative intestinal recovery,reduces complications,improves nutritional status,and shortens hospital stays in refractory functional constipation patients undergoing Jinling procedure,supporting its clinical adoption.