This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective: To investigate the characteristics and HIV confirmed positive status among individuals attending HIV voluntary counseling and testing (VCT) clinics in Inner Mongolia Autonomous Region, so as to provide the basis for enhancing interventions targeting high-risk populations for AIDS. Methods: Demographic information, reasons for consultation, consulting institutions, and HIV antibody testing data of individuals attending VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023 were collected through the VCT database of the Chinese Center for Disease Control and Prevention. The characteristics of individuals attending VCT were described. Factors affecting HIV confirmed positive among VCT clinic attendees were analyzed using a multivariable logistic regression model. Results: A total of 249 919 individuals attended VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023, including 128 069 males (51.24%) and 121 850 females (48.76%). The majority of attendees were aged 25-<35 years, accounting for 92 445 cases (36.99%). Among them, 785 cases were confirmed as HIV positive, with a positivity rate of 0.31%. Multivariable logistic regression analysis revealed that males (OR=4.787, 95%CI: 3.562-6.434), 45-<65 years of age (45-<55 years, OR=7.723, 95%CI: 1.786-33.406; 55-<65 years, OR=7.689, 95%CI: 1.757-33.653), being unmarried (OR=2.143, 95%CI: 1.580-2.906), junior high school education or below (OR=1.147, 95%CI: 1.042-2.430), having the history of high-risk behaviors or exposure risks (commercial heterosexual behaviors, OR=2.717, 95%CI: 1.707-4.324; non-commercial non-fixed heterosexual behaviors, OR=5.421, 95%CI: 3.763-7.809; homosexual behaviors, OR=70.774, 95%CI: 48.409-103.473; having an HIV-positive spouse/fixed partner/mother, OR=100.024, 95%CI: 62.490-160.100; drug injection, OR=5.366, 95%CI: 2.213-13.014), and seeking general hospitals or traditional Chinese medicine hospitals (OR=1.973, 95%CI: 1.650-2.360) were associated with a higher risk of HIV confirmed positive. Conclusions HIV confirmed positive among individuals attending VCT clinics in Inner Mongolia Autonomous Region is associated with gender, age, marital status, educational level, reasons for consultation, and consulting institutions. It is recommended to strengthen health education and targeted interventions for high-risk populations to reduce the risk of HIV infection.

Objective　Exploring the risk factors and degree of influence on treatment regression of patients with etiologically positive pulmonary tuberculosis in Bijie city, so as to provide reference for the precise prevention and treatment of pulmonary tuberculosis epidemic. Methods　The medical records of registration, treatment and management of pulmonary tuberculosis patients in Bijie City with positive etiology from 2017 to 2022 were derived from the Tuberculosis Monitoring Report Information Management System. Statistically significant variables were screened using binary logistic regression. Revealing interdependencies between factors and conditional probabilities by constructing Bayesian network models. 　Results　A total of 21 662 cases of etiologically positive pulmonary tuberculosis were registered in Bijie City from 2017 to 2022, with etiologically positive rate of 48.60% and a successful treatment rate of 89.52%, both of which were on the rise overall (χ2trend=2 618.15, P<0.001; χ2trend=102.84, P<0.001). A multifactorial analysis showed that gender, age, ethnicity, occupation, patient origin, HIV test results, migrating population, and treatment classification were influencing factor for the successful treatment rate (P<0.05). The Bayesian network model showed that age and treatment classification were the direct factors affecting the treatment outcome, while gender, occupation and patient origin were the indirect factors. Conditional probability showed that patients<20 years of age and initial treatment had the highest rate of successful treatment (96.75%), with a 3.25% probability of having an adverse outcome; Patients≥80 years of age who were retreated had the lowest rate of successful treatment (58.70%), with a 41.30% probability of having an adverse outcome. Conducting causal effect speculation, when preventing tuberculosis in older persons aged 60 years and over, and the other patients are newly treated patients, the successful treatment rate increased from 89.50% to 93.10%, with an increase of 3.60%; Nearly 50.00% fewer farmers are without tuberculosis, and the source of the other patients is active detection (health check-ups and proactive screening), with an increase in the successful treatment rate from 89.50% to 91.70%, with a change in the conditional probability value of 2.20%. Conclusions　Consultation and management of male, elderly, re-treatment, farmer, HIV-positive pulmonary tuberculosis patients in Bijie should be strengthened. Meanwhile, causal correlation effect inference using Bayesian networks is important for precise prevention, control and treatment of diseases.

OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.

OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

Objective: To investigate whether fibroblast growth factor 18(FGF18) can induce human gingival fibroblasts(HGFs) isolatedin vitroto differentiate into osteoblast-like cells, and to explore the mechanism of osteogenesis. Methods : HGFs were isolated, cultured and identified by tissue block method. The third generation of HGFs were divided into experimental group and control group. FGF18 and L-DMEM was added to the experimental group while L-DMEM was added to the control group.The effects of different concentrations of FGF18(0, 0.01, 0.02, 0.04, 0.06 mg/L) on proliferation of HGFs were detected by Methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay. Alkaline phosphatase(ALP) and alizarin red staining were used to detect the osteogenesis and mineralization ability of the cells after induction. RT-PCR, immunocytochemistry staining, and Western blot were used to detect the expression of genes and proteins related to osteogenesis and BMP2 in the BMP signaling pathway. Results: Compared with the control group, the experimental group could promote the proliferation of HGFs at 3, 5, 7, 9, and 11days(P<0.05),ALP activity and mineral salt deposition increased after induction at 14 and 21 days(P<0.05), and the expressions of ALP, OPN, OCN mRNA and BMP2 mRNA in BMP signaling pathway significantly increased(P<0.01). The expressions of OPN, OCN and BMP2 protein at 21 days were significantly higher than those at 14 days(P<0.01). Conclusion FGF18 can promote the proliferation of HGFs, and induce the differentiation of HGFs into functional osteoblasts. The osteogenic mechanism is related to the upregulation of BMP2.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

BACKGROUND:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing injury.As approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive Care(MIMIC-IV),a prediction system for the ED triage stage would be helpful.Previous methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to find a light-weight,convenient prediction method through machine learning. METHODS:We accessed the MIMIC-IV for sepsis patient data in the EDs.Our dataset comprised demographic information,vital signs,and synthetic features.Extreme Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED admission.Additionally,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's results.Ten percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold cross-validation. RESULTS:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±0.02.The model achieved similar performance on the testing set of 1,662 patients.SHAP values showed that the five most important features were acuity,arrival transportation,age,shock index,and respiratory rate. CONCLUSION:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage.This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

ObjectiveTo investigate the effect and mechanism of modified Guizhi Fulingwan in preventing colorectal adenoma （CRA） in mice by regulating mitochondrial apoptosis pathway through the regulation of the phosphatase and tensin homolog （PTEN）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty SPF-grade male C57BL/6 mice were randomly divided into six groups： Normal group， model group， low， medium， and high dose groups of modified Guizhi Fulingwan （13， 26， 52 g·kg^-1·d^-1）， and positive control aspirin group （0.015 g·kg^-1·d^-1）. A mouse model of CRA was chemically induced using azoxymethane （AOM） and dextran sulfate sodium （DSS）. During the modeling process， mice received modified Guizhi Fulingwan or aspirin. Body weight of mice was measured weekly during the treatment. After 9 weeks， the number of adenomas formed was observed. Serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the histopathologic changes in adenoma tissues. The expression of Cyclin D₁ and proliferative nuclear antigen （Ki67） was detected by immunohistochemistry （IHC）. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to assess the apoptosis in adenoma tissues. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to observe the mRNA and protein expression levels of PTEN， PI3K， Akt， phosphorylated PI3K （p-PI3K）， phosphorylated Akt （p-Akt）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， cytochrome C （Cyt C）， Caspase-9， and caspase-3. ResultCompared with the normal group， the model group showed no significant change in body weight from week 1 to week 2， but a significant decrease from week 3 to week 9 （P<0.05，P<0.01）. The colorectal length was significantly shortened， and the colorectal weight increased with visible varying sized tumor-like protrusions on the mucosal surface （P<0.01）. Serum levels of TNF-α， IL-6， and IL-1β were elevated （P<0.01）. Histopathology showed disordered epithelial gland structure， elongated nuclei with pathological mitosis， and numerous lymphocytic infiltrations in the lamina propria. The positive expression rates of Cyclin D₁ and Ki67 were significantly increased （P<0.01）， while the apoptosis rate of adenoma cells was significantly decreased （P<0.01）. Expression levels of PI3K， Akt， Bcl-2 mRNA and proteins， as well as p-PI3K and p-Akt proteins， were significantly increased （P<0.01）， whereas PTEN， Bax， Cyt C， Caspase-9， and Caspase-3 mRNA and protein levels were significantly decreased （P<0.05， P<0.01）. Compared with the model group， all drug treatment groups showed an increase in body weight （P<0.01）， decreased intestinal weight， increased colorectal length， reduced number of adenomas significantly （P<0.05， P<0.01）， and significantly lowered serum levels of TNF-α， IL-6， and IL-1β （P<0.01）. Histopathology indicated improved glandular structure and reduced neutrophil infiltration in the mucosal lamina propria. The positive expression rates of Cyclin D₁ and Ki67 significantly decreased （P<0.01）， while the apoptosis rate of adenoma cells significantly increased （P<0.05， P<0.01）. Expression levels of PI3K， Akt， Bcl-2 mRNA and proteins， and p-PI3K and p-Akt proteins were significantly reduced （P<0.05， P<0.01）， while PTEN， Bax， Cyt C， Caspase-9， and Caspase-3 mRNA and protein levels significantly increased （P<0.05， P<0.01）. The high-dose modified Guizhi Fulingwan group exhibited the most significant intervention effects. ConclusionModified Guizhi Fulingwan may prevent CRA in mice by regulating the PTEN/PI3K/Akt signaling pathway and inducing the mitochondrial apoptosis pathway.