Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective To explore a method for rapid and differential diagnosis of rejection after kidney transplantation through urine hyperspectral imaging technology. Methods Hyperspectral data information from urine samples of 118 recipients after kidney transplantation was collected, and a deep learning model was constructed to diagnose and classify the types of rejection. Results A deep learning diagnostic model based on the 34-layer residual network (ResNet-34) was constructed, and 118 patients were included and divided into the training set and the test set. Based on the pathological results of the transplanted kidney puncture, the urine samples of the patients were classified into five groups: the non-rejection group, the T-cell-mediated rejection group, the antibody-mediated rejection group, the mixed rejection group and the nephropathy recurrence group. The results showed that the diagnostic sensitivities of the model for the above five groups were 0.960, 0.980, 0.930, 0.940 and 0.943 respectively, and the diagnostic specificities were 0.983, 0.993, 0.997, 0.989 and 0.989 respectively. The overall diagnostic accuracy rate reached 95.7%. Conclusions The study provides a non-invasive, rapid and accurate auxiliary diagnostic method for the differential diagnosis of rejection after kidney transplantation.

Objective To analyze the application of dual-energy CT virtual monoenergetic imaging(Mono+)technology com-bined with personalized contrast agent injection protocols in the diagnosis of lower extremity artery atherosclerosis in diabetes patients.Methods A total of 102 diabetes patients with suspected lower extremity artery atherosclerosis were selected.All patients received dual-energy CT Mono+technology combined with personalized contrast agent injection protocols.Based on personalized contrast agent injection protocols,the patients were divided into group A(34 cases,1.5 m L/kg),group B(34 cases,1.2 m L/kg),and group C(34 cases,1.0 m L/kg).All patients underwent dual-source CT scanning,and the results of ultrasound Doppler vascular imaging within one week were used as the gold standard to evaluate the consistency between dual-energy CT Mono+technology and ultra-sound Doppler vascular imaging under personalized contrast agent injection protocols.Results The CT values,signal-to-noise ratio and contrast-to-noise ratio of the abdominal iliac segment,femoral popliteal segment and lower knee segment in group B were higher than those in group A and group C(P<0.05).The CT values of the femoral popliteal and lower knee segments in group C were higher than those in group A(P<0.05).Among the 102 diabetes patients,84 were diagnosed with lower extremity artery athero-sclerosis confirmed by ultrasound Doppler vascular imaging.The positive predictive values for diagnosing lower extremity artery ath-erosclerosis in groups A,B,and C were 93.90%,97.65%,and 93.98%,respectively.The negative predictive values were 65.00%,94.14%,and 68.42%,respectively.The consistency with ultrasound Doppler vascular imaging was 0.690,0.897,and 0.715,respec-tively.Group B exhibited a higher diagnostic accuracy than groups A and C(P<0.05).Conclusion The dual-energy CT Mono+technology combined with personalized contrast agent injection protocols demonstrate good efficacy in diagnosing lower extremity artery atherosclerosis in diabetes patients,with the best imaging quality observed with the contrast agent injection protocol of 1.2 m L/kg.

Objective To analyze the MRI imaging characteristics of brain metastases in non-small cell lung cancer(NSCLC)with different epidermal growth factor receptor(EGFR)mutation types and programmed cell death-ligand 1(PD-L1)expression,and to provide imaging diagnostic support for patients who can't undergo genetic and immunohistochemical testing.Methods A retrospec-tive selection was performed in 88 patients diagnosed with brain metastases of NSCLC,all patients were divided into EGFR mutation group and wild group according to the results of genetic testing,and patients with EGFR mutation group were divided into EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expression negative group according to whether the expression of PD-L1 was≥1％.The clinical data and MR image characteristics of brain metastases were compared in EGFR mutation group and wild group,as well as in EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expres-sion negative group.Results There were statistically significant differences in smoking history and intracranial symptoms between EGFR mutation group and wild group(P＜0.05).The edema diameter,edema index and enhancement ratio of EGFR mutation group and wild group were(0.67±1.10)cm,0.39±0.54,0.32±0.17 and(1.57±2.04)cm,1.05±1.21,0.53±0.27,respectively,and the differences were statistically significant(P＜0.05).There were 43 cases and 23 cases in EGFR mutation group and wild group with ≥2 metastases,respectively,and the difference was statistically significant(P＜0.05).Compared with＞60 years old,there were 15 patients(75％)of EGFR mutation with PD-L1 expres-sion positive in≤60 years old(P＜0.05).Conclusion Compared with EGFR wild patients,patients with EGFR mutation have more brain metastases(≥2),milder enhancement,less peritumoral edema,and fewer intracranial symptoms at initial diagnosis,and patients with EGFR mutation aged≤60 years are more likely to have PD-L1 expression positive.

Objective To analyze the application of dual-energy CT virtual monoenergetic imaging(Mono+)technology com-bined with personalized contrast agent injection protocols in the diagnosis of lower extremity artery atherosclerosis in diabetes patients.Methods A total of 102 diabetes patients with suspected lower extremity artery atherosclerosis were selected.All patients received dual-energy CT Mono+technology combined with personalized contrast agent injection protocols.Based on personalized contrast agent injection protocols,the patients were divided into group A(34 cases,1.5 m L/kg),group B(34 cases,1.2 m L/kg),and group C(34 cases,1.0 m L/kg).All patients underwent dual-source CT scanning,and the results of ultrasound Doppler vascular imaging within one week were used as the gold standard to evaluate the consistency between dual-energy CT Mono+technology and ultra-sound Doppler vascular imaging under personalized contrast agent injection protocols.Results The CT values,signal-to-noise ratio and contrast-to-noise ratio of the abdominal iliac segment,femoral popliteal segment and lower knee segment in group B were higher than those in group A and group C(P<0.05).The CT values of the femoral popliteal and lower knee segments in group C were higher than those in group A(P<0.05).Among the 102 diabetes patients,84 were diagnosed with lower extremity artery athero-sclerosis confirmed by ultrasound Doppler vascular imaging.The positive predictive values for diagnosing lower extremity artery ath-erosclerosis in groups A,B,and C were 93.90%,97.65%,and 93.98%,respectively.The negative predictive values were 65.00%,94.14%,and 68.42%,respectively.The consistency with ultrasound Doppler vascular imaging was 0.690,0.897,and 0.715,respec-tively.Group B exhibited a higher diagnostic accuracy than groups A and C(P<0.05).Conclusion The dual-energy CT Mono+technology combined with personalized contrast agent injection protocols demonstrate good efficacy in diagnosing lower extremity artery atherosclerosis in diabetes patients,with the best imaging quality observed with the contrast agent injection protocol of 1.2 m L/kg.

Objective To analyze the MRI imaging characteristics of brain metastases in non-small cell lung cancer(NSCLC)with different epidermal growth factor receptor(EGFR)mutation types and programmed cell death-ligand 1(PD-L1)expression,and to provide imaging diagnostic support for patients who can't undergo genetic and immunohistochemical testing.Methods A retrospec-tive selection was performed in 88 patients diagnosed with brain metastases of NSCLC,all patients were divided into EGFR mutation group and wild group according to the results of genetic testing,and patients with EGFR mutation group were divided into EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expression negative group according to whether the expression of PD-L1 was≥1％.The clinical data and MR image characteristics of brain metastases were compared in EGFR mutation group and wild group,as well as in EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expres-sion negative group.Results There were statistically significant differences in smoking history and intracranial symptoms between EGFR mutation group and wild group(P＜0.05).The edema diameter,edema index and enhancement ratio of EGFR mutation group and wild group were(0.67±1.10)cm,0.39±0.54,0.32±0.17 and(1.57±2.04)cm,1.05±1.21,0.53±0.27,respectively,and the differences were statistically significant(P＜0.05).There were 43 cases and 23 cases in EGFR mutation group and wild group with ≥2 metastases,respectively,and the difference was statistically significant(P＜0.05).Compared with＞60 years old,there were 15 patients(75％)of EGFR mutation with PD-L1 expres-sion positive in≤60 years old(P＜0.05).Conclusion Compared with EGFR wild patients,patients with EGFR mutation have more brain metastases(≥2),milder enhancement,less peritumoral edema,and fewer intracranial symptoms at initial diagnosis,and patients with EGFR mutation aged≤60 years are more likely to have PD-L1 expression positive.

OBJECTIVE To explore the effects of levosimendan on cardiac function， hemodynamics and prognosis of patients with septic shock complicated with myocardial depression， and evaluate the safety of levosimendan. METHODS Patients with septic shock complicated with myocardial depression who were admitted to the Department of Critical Care Medicine of Chongqing University Three Gorges Hospital from April 2021 to August 2023， underwent adequate fluid resuscitation， had a mean arterial pressure （MAP） ≥65 mmHg， and received pulse indicator continuous cardiac output （PiCCO） monitoring were enrolled. The patients were randomly divided into dobutamine group and levosimendan group according to a random number table， with 20 patients in each group. Both groups received intravenous infusion of Norepinephrine bitartrate injection at a dose of 0.1-2.0 μg/（kg·min）. On this basis， the dobutamine group additionally received intravenous infusion of Dobutamine hydrochloride injection at a dose of 5- 10 μg/（kg·min） for 3 to 7 days， while the levosimendan group additionally received intravenous infusion of Levosimendan injection at a dose of 0.1-0.2 μg/（kg·min） for 24 hours. Heart rate （HR） and hemodynamic parameters [systolic blood pressure， diastolic blood pressure， MAP， central venous pressure （CVP）]， PiCCO monitoring parameters [cardiac function index （CFI）， cardiac index （CI）， stroke volume index （SVI）， extravascular lung water index， global end-diastolic volume index， pulmonary vascular permeability index （PVPI）， global ejection fraction （GEF）， systemic vascular resistance index， left ventricular contractility index]， and prognosis indicators [death within 3 days after administration， mechanical ventilation time，intensive care unit （ICU） stay time， 28-day mortality rate] were compared between the two groups before treatment and at 24 and 72 hours after treatment. Adverse reactions were E-mail：recorded for both groups. RESULTS Compared with before treatment in the same group， CFI， CI and GEF at 24 hours after treatment， CI and GEF at 72 hours after treatment in the dobutamine group， as well as SVI at 24 hours after treatment and SVI and GEF at 72 hours after treatment in the levosimendan group were significantly increased； PVPI at 72 hours after treatment in the dobutamine group was significantly decreased （P＜0.05）. Compared with the dobutamine group during the same period， patients in the levosimendan group had significantly lower HR and significantly higher CVP at 24 hours after treatment （P＜0.05）. Within 3 days after administration， there were no deaths in either group； there were no statistically significant differences in mechanical ventilation time， ICU stay time， 28-day mortality rate， or the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS For patients with septic shock complicated with myocardial depression who have undergone adequate fluid resuscitation and have a MAP of ≥65 mmHg， levosimendan is comparable to dobutamine in improving cardiac function and hemodynamic parameters， without affecting patients’ prognosis or increasing the risk of adverse reactions such as hypotension.

Objective:To summarize the clinicopathologic characteristics of undifferentiated embryonal sarcoma of the liver.Methods:The clinical data of 16 patients with undifferentiated embryonal sarcoma of the liver admitted to Shandong Provincial Hospital and Yantai Yuhuangding Hospital from Jan 2000 to Jan 2023 was retrospectively analyzed.Results:The diagnosis of undifferentiated embryonal sarcoma in all the 16 patients was established by postoperative pathology. The clinical manifestations of the patients were mainly asymptomatic abdominal mass, abdominal pain and discomfort. The laboratory examination was mostly nonspecific, the image exam showed mostly solid cystic mass. 14 cases underwent radical surgical resection.The minimum survival time was 7 months, maximum survival time was 121 months with median survival time of 35.9 months.Conclusions:Undifferentiated embryonal sarcoma of the liver is an extremely rare malignant tumor of the liver. The disease lacks specific clinical manifestations. CT examination can assist in the diagnosis of the disease. Diagnosis of undifferentiated embryonal sarcoma of the liver depends on pathological examination. The prognosis of patients is poor, surgical resection of the tumor is an effective treatment.

Six patients with factor Ⅴ deficiency were admitted in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2006 to December 2022. All 6 patients presented with symptoms of coagulation dysfunction, 4 patients had recurrent nose bleeding, gingival bleeding, skin ecchymosis as the main manifestations, 1 patient had lower abdominal pain and ovarian active bleeding, and 1 patient had heavy menstruation. The prothrombin time and activated partial thromboplastin time were significantly prolonged, the factor Ⅴ level was significantly lower than normal, and the thrombin time was basically normal in all patients. Four patients received non-surgical treatment and transfusion of fresh frozen plasma; the bleeding symptoms were significantly relieved during hospitalization, and no aggravation of bleeding symptoms was found during follow-up. One patient with active ovarian hemorrhage underwent emergency surgical suture to stop bleeding, and fresh frozen plasma and prothrombin complex were given perioperatively; and no more bleeding occurred during follow-up. One patients with excessive menstruation underwent curettage plus hysteroscopic endometrial ablation, and the amount of menstruation was significantly reduced. It is suggested that the bleeding symptoms of coagulation factor Ⅴ deficiency vary in severity, which can be effectively alleviated by infusion of the fresh frozen plasma in most cases.