Drug-target interaction (DTI) is fundamental to novel drug research and development (R &D), playing a critical role in elucidating drug mechanisms of action and improving the cost-effectiveness of drug discovery. Although China has seen rapid accumulation of drug-target resources in recent years, the industry still faces challenges such as a shortage of original targets and excessively high target concentration. The rapid advancement of artificial intelligence (AI) has provided an efficient technological pathway for DTI prediction, establishing it as a core tool for accelerating drug discovery. This paper systematically reviews the fundamental data support framework for DTI prediction tasks, elaborating in detail on three core data types— drug characterization, target characterization, and drug-target associations-as well as the classification and application boundaries of mainstream benchmark datasets tailored to different tasks within the field. On this basis, it comprehensively surveys the technological evolution of AI-driven DTI prediction, summarizing the core paradigms and technical advances of traditional machine learning and deep learning methods in a single-modality setting, alongside cutting-edge multimodal approaches that integrate two modalities (cross-subject/within-subject fusion) and three or more modalities for multidimensional information integration. Finally, this paper analyzes the current major challenges in data quality, model generalizability and interpretability, and real-world deployment, while also discussing future trends in standardized dataset construction, generative AI, and large-scale biomedical foundation models, aiming to provide a reference for both research and industrial applications in the AI-driven DTI prediction field.

Objective To explore the clinical characteristics and risk factors of upper urinary tract stones complicated with non-alcoholic fatty liver disease(NAFLD),so as to provide reference for the prevention of this disease.Methods The clinical data of 158 NAFLD patients undergoing surgical treatment in our hospital during Jan.2022 and Jul.2023 were retrospectively analyzed.According to whether the patients were complicated with NAFLD,they were divided into the NAFLD group(n=56)and non-NAFLD group(n=102).The general data,laboratory indexes and 24-h urinary metabolic indexes were compared between the two groups,and the risk factors were analyzed with univariate and multivariate logistic regression analyses.Results Compared with the non NAFLD group,the NAFLD group had higher BMI[(28.17±4.17)vs.(24.11±3.72),P＜0.001],blood uric acid[(354.13±111.01)μmol/L vs.(294.41±93.72)μmol/L,P＜0.001],and 24-h urinary oxalate level[(37.74±15.00)mmol vs.(27.73±15.27)mmol,P＜0.001].Multivariate logistic analysis showed that BMI(OR=1.311,P＜0.001),24-h urinary oxalate(OR=1.046,P=0.004),and 24-h urinary magnesium(OR=0.599,P=0.002)were the independent factors for NAFLD with upper urinary tract stones.Conclusion NAFLD complicated with upper urinary tract stones is significantly associated with high BMI,high 24-h urinary oxalate,and low 24-h urinary magnesium.

This article reviews the research advances in the characteristics and application progress of various new models for preclinical cancer research on pancreatic cancer， analyzes and discusses the history， current research status， and advantages and disadvantages of new models of pancreatic cancer， including patient-derived tissue xenograft， conditional reprogramming， and patient derived organoids， and it also reviews the studies that have achieved clinical transformation from preclinical models and proposes possible research prospects in the future.

Objective To explore the clinical characteristics and treatment methods of female primary enteric adenocarcinoma of the urethra.Methods The diagnosis and treatment of one case were reported.The origin,etiology,imaging findings,diagnosis,treatment,and prognosis were discussed in combination with relevant literature.Results The patient is a 61-year-old female,visited our hospital due to vaginal odor complicated with urethral bleeding for 2 months,and was diagnosed with urethral adenocarcinoma after examination.She underwent partial urethral resection,urethral meatus shaping and temporary bladder fistula surgery,with negative resection margins.However,local recurrence occurred 7 months after surgery.The patient was readmitted for a second time,undergoing laparoscopic total urethral resection,anterior vaginal wall resection,bladder neck resection,and permanent bladder fistulation,followed by chemotherapy.At the 19th month after the first surgery,the patient was admitted due to tumor recurrence,and the third surgery consisted of total bladder and uterus resection,ileal neobladder,and perineal closure.Postoperative pathology indicated urethral adenocarcinoma originating from the intestines.During the 39-month follow-up,the tumor recurred twice.No recurrence or metastasis was observed after the final total pelvic exenteration.Conclusion Enteric adenocarcinoma of the urethra is extremely rare.Comprehensive treatment including surgery,radiotherapy,and chemotherapy may prolong survival,but the overall prognosis is poor,requiring long-term follow-up.

OBJECTIVE To investigate the mechanism through which Chaixian Huashen decoction(CXHSD)ameliorates lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.METHODS Component analysis:the components of CXHSD extract were analyzed via ultra-high performance liquid chromatography-high resolution mass spectrometry(UPLC-Q-Exactive HFX).Network pharma-cology analysis was conducted to predict the potential active components and underlying therapeutic targets of CXHSD for ALI treatment.① Animal experiment:mice were randomly divided into the normal control group,model(LPS)group,model+dexamethasone(DEX)4 mg·kg-1 group,model+CXHSD 10 g·kg-1 group,and model+CXHSD 20 g·kg-1 group.Except for the normal control group,ALI was induced in all the mice by intratracheal instillation of LPS.Model+CXHSD groups received daily intra-gastric administration of corresponding treatments for 7 consecutive days.The model+DEX group was administered saline intragastrically for the initial 5 d,followed by DEX for the next 2 d.ALI was induced by intratracheal instillation of LPS 5 mg·kg-1 1 h after the 6th administration of CXHSD/DEX.24 h after modeling,the severity of pulmonary edema was assessed using the wet to dry weight(W/D)ratio,and hematoxylin-eosin(HE)staining was used to evaluate histopathological damage.The levels of myeloperoxidase(MPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β in lung tissue homogenates and serum were measured by enzyme-linked immunosorbent assay(ELISA).The total protein concentration in bronchoalveolar lavage fluid(BALF)was measured by bicinchoninic acid(BCA)assay.Immunohistochemistry and Western blotting were used to assess the expression levels of toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),zonula occludens-1(ZO-1)and occludin,as well as the phosphorylation level of nuclear factor-kappa B p65(NF-κB p65).② Cell experiment:RAW264.7 cells were divided into the cell control group,LPS 1 mg·L-1 group,LPS 1 mg·L-1+DEX 1 mg·L-1 group,and LPS 1 mg·L-1+CXHSD 50,100 and 200 mg·L-1 groups.After 24 h of culture,the nitric oxide(NO)content was measured with the nitrate reductase method,the levels of TNF-α,IL-1 β and IL-6 in the cell supernatants of each group were detected by ELISA.RESULTS Network pharmacology analysis indicated that CXHSD might alleviate ALI through the NF-κB pathway.① Com-pared with the normal control group,the W/D ratio was elevated,pathological injuries aggravated(such as alveolar wall thickening,inflammatory infiltration,and alveolar congestion),histopathological damage pronounced,MPO activity increased,and total protein concentrations in BALF raised in the model group,in which levels of TNF-α,IL-6 and IL-1 β in both lung tissue and serum became higher.Concur-rently,LPS increased the expressions of p-NF-κB p65,TLR4 and MyD88,but reduced the expressions of ZO-1 and occludin.Compared with the model group,model+CXHSD groups had their pulmonary edema and lung pathological injury ameliorated as evidenced by alleviated alveolar wall thickening,inflammatory infiltration and alveolar congestion.The levels of MPO,TNF-α,IL-1 β and IL-6 in both lung tissue and serum,and the total protein concentrations in BALF were significantly decreased in the model+CXHSD groups.Additionally,the expressions of TLR4,MyD88,and p-NF-κB p65 were significantly downregulated,while those of ZO-1 and occludin were prominently upregulated.② Compared with the cell control,the levels of TNF-α,IL-1 β,IL-6 and NO in the supernatant of RAW264.7 cells were signifi-cantly increased in the LPS group.Compared with the LPS group,in the supernatant of RAW264.7 cells treated with LPS+CXHSD at 100 mg·L-1,there was no significant difference in TNF-α levels.However,in the other groups treated with LPS+CXHSD,the levels of TNF-α,IL-1 β,IL-6,and the content of NO were significantly reduced.CONCLUSION CXHSD can alleviate LPS-induced ALI by inhibiting the TLR4/NF-κB pathway,attenuating inflammation,and preserving pulmonary barrier integrity.

Objective To explore the clinical characteristics and treatment methods of female primary enteric adenocarcinoma of the urethra.Methods The diagnosis and treatment of one case were reported.The origin,etiology,imaging findings,diagnosis,treatment,and prognosis were discussed in combination with relevant literature.Results The patient is a 61-year-old female,visited our hospital due to vaginal odor complicated with urethral bleeding for 2 months,and was diagnosed with urethral adenocarcinoma after examination.She underwent partial urethral resection,urethral meatus shaping and temporary bladder fistula surgery,with negative resection margins.However,local recurrence occurred 7 months after surgery.The patient was readmitted for a second time,undergoing laparoscopic total urethral resection,anterior vaginal wall resection,bladder neck resection,and permanent bladder fistulation,followed by chemotherapy.At the 19th month after the first surgery,the patient was admitted due to tumor recurrence,and the third surgery consisted of total bladder and uterus resection,ileal neobladder,and perineal closure.Postoperative pathology indicated urethral adenocarcinoma originating from the intestines.During the 39-month follow-up,the tumor recurred twice.No recurrence or metastasis was observed after the final total pelvic exenteration.Conclusion Enteric adenocarcinoma of the urethra is extremely rare.Comprehensive treatment including surgery,radiotherapy,and chemotherapy may prolong survival,but the overall prognosis is poor,requiring long-term follow-up.

OBJECTIVE To investigate the mechanism through which Chaixian Huashen decoction(CXHSD)ameliorates lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.METHODS Component analysis:the components of CXHSD extract were analyzed via ultra-high performance liquid chromatography-high resolution mass spectrometry(UPLC-Q-Exactive HFX).Network pharma-cology analysis was conducted to predict the potential active components and underlying therapeutic targets of CXHSD for ALI treatment.① Animal experiment:mice were randomly divided into the normal control group,model(LPS)group,model+dexamethasone(DEX)4 mg·kg-1 group,model+CXHSD 10 g·kg-1 group,and model+CXHSD 20 g·kg-1 group.Except for the normal control group,ALI was induced in all the mice by intratracheal instillation of LPS.Model+CXHSD groups received daily intra-gastric administration of corresponding treatments for 7 consecutive days.The model+DEX group was administered saline intragastrically for the initial 5 d,followed by DEX for the next 2 d.ALI was induced by intratracheal instillation of LPS 5 mg·kg-1 1 h after the 6th administration of CXHSD/DEX.24 h after modeling,the severity of pulmonary edema was assessed using the wet to dry weight(W/D)ratio,and hematoxylin-eosin(HE)staining was used to evaluate histopathological damage.The levels of myeloperoxidase(MPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β in lung tissue homogenates and serum were measured by enzyme-linked immunosorbent assay(ELISA).The total protein concentration in bronchoalveolar lavage fluid(BALF)was measured by bicinchoninic acid(BCA)assay.Immunohistochemistry and Western blotting were used to assess the expression levels of toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),zonula occludens-1(ZO-1)and occludin,as well as the phosphorylation level of nuclear factor-kappa B p65(NF-κB p65).② Cell experiment:RAW264.7 cells were divided into the cell control group,LPS 1 mg·L-1 group,LPS 1 mg·L-1+DEX 1 mg·L-1 group,and LPS 1 mg·L-1+CXHSD 50,100 and 200 mg·L-1 groups.After 24 h of culture,the nitric oxide(NO)content was measured with the nitrate reductase method,the levels of TNF-α,IL-1 β and IL-6 in the cell supernatants of each group were detected by ELISA.RESULTS Network pharmacology analysis indicated that CXHSD might alleviate ALI through the NF-κB pathway.① Com-pared with the normal control group,the W/D ratio was elevated,pathological injuries aggravated(such as alveolar wall thickening,inflammatory infiltration,and alveolar congestion),histopathological damage pronounced,MPO activity increased,and total protein concentrations in BALF raised in the model group,in which levels of TNF-α,IL-6 and IL-1 β in both lung tissue and serum became higher.Concur-rently,LPS increased the expressions of p-NF-κB p65,TLR4 and MyD88,but reduced the expressions of ZO-1 and occludin.Compared with the model group,model+CXHSD groups had their pulmonary edema and lung pathological injury ameliorated as evidenced by alleviated alveolar wall thickening,inflammatory infiltration and alveolar congestion.The levels of MPO,TNF-α,IL-1 β and IL-6 in both lung tissue and serum,and the total protein concentrations in BALF were significantly decreased in the model+CXHSD groups.Additionally,the expressions of TLR4,MyD88,and p-NF-κB p65 were significantly downregulated,while those of ZO-1 and occludin were prominently upregulated.② Compared with the cell control,the levels of TNF-α,IL-1 β,IL-6 and NO in the supernatant of RAW264.7 cells were signifi-cantly increased in the LPS group.Compared with the LPS group,in the supernatant of RAW264.7 cells treated with LPS+CXHSD at 100 mg·L-1,there was no significant difference in TNF-α levels.However,in the other groups treated with LPS+CXHSD,the levels of TNF-α,IL-1 β,IL-6,and the content of NO were significantly reduced.CONCLUSION CXHSD can alleviate LPS-induced ALI by inhibiting the TLR4/NF-κB pathway,attenuating inflammation,and preserving pulmonary barrier integrity.

Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group，the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters，stone-removal rate，complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L，P=0.001]，difference in the white blood cell (WBC) level [(0.24±2.12)×10 cells/L vs. (1.19±2.17)×10 cells/L，P=0.016]，incidence of fever (2.8% vs. 16.9%，P=0.028) and overall complication rate (5.6% vs. 19.6%，P=0.042) were significantly lower in the dual-control group than in the conventional group，while the stone-clearance rate was slightly higher (88.9% vs. 82.5%，P=0.346)，with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm，intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications，which is worthy of clinical promotion.

OBJECTIVE To compare the efficacy of ceftazidime and avibactam （CZA） monotherapy and combination therapy in the treatment of carbapenem-resistant Gram-negative bacteria （CRGNB） infections， and analyze the influencing factors. METHODS The data of patients with CRGNB infection who received CZA treatment from January 2020 to March 2025 were collected retrospectively. The patients were divided into the CZA monotherapy group （52 cases） and the CZA combination therapy group （85 cases） according to treatment regimen. The therapeutic effects of the two groups were compared， and the drug susceptibility results of isolated strains were recorded. The multivariate Logistic regression model was used to analyze the factors influencing clinical efficacy of CRGNB patients. RESULTS The bacterial clearance rate of patients was significantly higher in the CZA combination therapy group than in the CZA monotherapy group （P＝0.012）. However， when comparing the 30-day mortality rate and the clinical response rate between the two groups， no statistically significant differences were observed （P＞0.05）. Among the isolates， carbapenem-resistant Klebsiella pneumoniae had the highest sensitivity to tigecycline （87.3%） and carbapenem-resistant Pseudomonas aeruginosa showed 90.9% sensitivity to amikacin. Five isolates were resistant to CZA. The multivariate Logistic regression showed， lung infection， receiving continuous renal replacement therapy （CRRT）， and inadequate treatment courses were significantly correlated with clinical treatment failure （P＜0.05）. CONCLUSIONS For CRGNB infection， the clinical efficacy of CZA combination therapy is similar to that of monotherapy， but the combination therapy has a higher bacterial clearance rate. Lung infections， receiving CRRT and inadequate treatment courses （No. are independent risk factors for clinical treatment failure.

Objective:To investigate the independent risk factors for the occurrence of early urinary incontinence after Holmium laser enucleation of the prostate(HoLEP), and to construct a clinical risk predictive model for postoperative urinary incontinence.Methods:A retrospective analysis was conducted on the clinical data of 384 patients who underwent HoLEP between February 2019 and July 2024 at the Second Affiliated Hospital of Zhengzhou University. The cohort had a mean age of (68.3 ± 6.5) years, with a body mass index (BMI) of 22.45 (20.11, 24.39) kg/m 2. The median duration of lower urinary tract symptoms was 60 (36, 60) months. Of the patients, 104 (27.1%) had a history of diabetes mellitus, 139 (36.2%) had hypertension, and 54 (14.1%) had a preoperative indwelling urinary catheter. Additionally, 136 patients (35.4%) had a preoperative prostate-specific antigen (PSA) level ≥ 4 ng/ml, and 197 patients (51.3%) had a preoperative residual urine volume ≥ 50 ml. The International Prostate Symptom Score (IPSS) was ≥ 19 in 227 cases (59.1%). Preoperative detrusor instability was observed in 169 cases (44.0%), with a median maximal urinary flow rate of 5.9 (4.5, 9.3) ml/s and a median urinary flow rate of 4.0 (3.4, 7.3) ml/s. Moreover, 148 cases (38.5%) had a preoperative prostate volume ≥ 65 ml, and the preoperative median maximum urethral length (MUL) was 13.99 (12.40, 16.24) mm. Postoperative follow-up allowed for division of the patients into two groups: those with recovery of urinary control function and those with early postoperative urinary incontinence. The general characteristics of both groups were compared. Independent risk factors for early postoperative urinary incontinence were identified through multifactorial logistic regression. Variables with statistically significant differences were included in a column chart model created using R software. Internal validation was performed through repeated sampling with the Bootstrap method to assess the model's discriminative ability. Calibration curves were plotted to examine the consistency between predicted and actual outcomes, and the Hosmer-Lemeshow test was used to evaluate the model's fit. Results:This study included 384 patients, with 313 in the urinary control function recovery group and 71 in the early incontinence group. There were statistically significant difference between the two groups in age [≥70 years old: 91 (29.1%) vs. 33 (46.5%)], prostate volume [≥65 ml: 110 (35.1%) vs. 38 (53.5%)], MUL [14.21 (12.63, 16.24) mm vs. 13.12 (12.21, 13.95) mm], and non-inhibitory contraction of the urethra muscle in both groups [125 (39.9%) vs. 44 cases (62.0%)] ( P < 0.05). No significant differences were observed between the two groups in terms of BMI, disease duration, history of diabetes mellitus, preoperative catheterization, IPSS, preoperative PSA, residual bladder urine volume, maximum urinary flow rate, average urinary flow rate, operative time, or duration of indwelling urinary catheterization ( P > 0.05). Multifactorial logistic regression analysis revealed that age ≥ 70 years ( OR = 0.414, 95% CI 0.230-0.746, P = 0.003), prostate volume ≥ 65 ml ( OR=0.451, 95% CI 0.251-0.812, P=0.008), MUL( OR=0.688, 95% CI 0.590-0.802, P<0.001), and detrusor instability, uninhibited detrusor contraction ( OR=0.526, 95% CI 0.279-0.994, P=0.048) were independent risk factors for early postoperative urinary incontinence following HoLEP. A prediction model was developed based on these findings, and internal validation showed a C-index of 0.753. The calibration curve was close to the ideal curve, indicating that the model has good predictive performance. Conclusions:Age ≥70 years, prostate volume ≥65 ml, MUL, and uninhibited contraction of the urethra muscle were independent influences on early urinary incontinence after HoLEP, and the nomogram constructed in this way had good predictive performance for the risk of developing early urinary incontinence after HoLEP.