OBJECTIVE To develop physiologically based pharmacokinetic （PBPK） model for sodium tanshinone Ⅱ A sulfonate （STS）， clopidogrel （Clo）， and its metabolites， to predict the potential drug-drug interaction （DDI） between STS and Clo during co-administration， and to identify the key factors influencing the predicte d DDI， and provide evidence for rational clinical medication. METHODS Physicochemical and pharmacokinetic parameters of Clo， its metabolites， and STS were retrieved from PubMed， DrugBank， and SwissADME for PBPK model development. The steady-state area under the plasma concentration-time curve （AUC） and maximum concentration （ c max ） of clopidogrel thiol H4 （Clo-AM） were used as indicators to evaluate the DDI between STS and Clo. Single-factor sensitivity analysis was performed to identify key parameters influencing DDI between STS and Clo during co-administration. RESULTS Compared with Clo alone， after 7 days of Clo combined with STS 40 mg， the AUC ratio and c max ratio of Clo-AM were 0.75 and 0.63， respectively. When the dose of STS was increased to 80 mg， the AUC ratio and c max ratio of Clo-AM were 0.62 and 0.56， respectively. Sensitivity analysis indicated that the absolute values of normalized sensitivity coefficients for the lipophilicity of Clo-AM， the inhibition constants of STS for CYP2C19 and CYP3A4， and the hepatic clearance of Clo-AM were 15.19， 11.34， 10.98， 3.08， respectively. These parameters were the highly sensitive parameters in the DDI between STS and Clo during co-administration. CONCLUSIONS The established PBPK model can be used to predict the DDI between STS and Clo during co-administration. Co-administration of STS and Clo may lead to decreased exposure of Clo-AM. The lipophilicity-related parameters of Clo-AM and the inhibition parameters related to CYP3A4 and CYP2C19 are key parameters influencing the prediction of Clo-AM exposure， among which the inhibitory effects of STS on CYP3A4 and CYP2C19 may be an important mechanism mediating the DDI between STS and Clo.

OBJECTIVE To develop physiologically based pharmacokinetic （PBPK） model for sodium tanshinone Ⅱ A sulfonate （STS）， clopidogrel （Clo）， and its metabolites， to predict the potential drug-drug interaction （DDI） between STS and Clo during co-administration， and to identify the key factors influencing the predicte d DDI， and provide evidence for rational clinical medication. METHODS Physicochemical and pharmacokinetic parameters of Clo， its metabolites， and STS were retrieved from PubMed， DrugBank， and SwissADME for PBPK model development. The steady-state area under the plasma concentration-time curve （AUC） and maximum concentration （ c max ） of clopidogrel thiol H4 （Clo-AM） were used as indicators to evaluate the DDI between STS and Clo. Single-factor sensitivity analysis was performed to identify key parameters influencing DDI between STS and Clo during co-administration. RESULTS Compared with Clo alone， after 7 days of Clo combined with STS 40 mg， the AUC ratio and c max ratio of Clo-AM were 0.75 and 0.63， respectively. When the dose of STS was increased to 80 mg， the AUC ratio and c max ratio of Clo-AM were 0.62 and 0.56， respectively. Sensitivity analysis indicated that the absolute values of normalized sensitivity coefficients for the lipophilicity of Clo-AM， the inhibition constants of STS for CYP2C19 and CYP3A4， and the hepatic clearance of Clo-AM were 15.19， 11.34， 10.98， 3.08， respectively. These parameters were the highly sensitive parameters in the DDI between STS and Clo during co-administration. CONCLUSIONS The established PBPK model can be used to predict the DDI between STS and Clo during co-administration. Co-administration of STS and Clo may lead to decreased exposure of Clo-AM. The lipophilicity-related parameters of Clo-AM and the inhibition parameters related to CYP3A4 and CYP2C19 are key parameters influencing the prediction of Clo-AM exposure， among which the inhibitory effects of STS on CYP3A4 and CYP2C19 may be an important mechanism mediating the DDI between STS and Clo.

OBJECTIVE To explore a new model of intelligent medication education for pharmaceutical outpatient clinics by constructing dynamic HTML web pages through the DeepSeek-V3-0324 large-scale model. METHODS Clinical pharmacists integrated key clinical information such as patients’ basic information， medication history and medication precautions in real time， and generated a standardized medication education list through the DeepSeek-V3-0324 large-scale model and manual review. RESULTS The DeepSeek-V3-0324 large-scale model was applied in the pharmaceutical outpatient clinics to generate a personalized medication education list， which could effectively solve the disunity of pharmacy guidance caused by the lack of standardization of medication education and the difference of individualized experience of pharmacists in the traditional pharmaceutical outpatient clinics in the face of complex cases， and medication errors caused by forgetting or misremembering information among certain special patient populations after receiving medication education. CONCLUSIONS The transformation and application of artificial intelligence technology in pharmaceutical outpatient clinics is an innovation of pharmaceutical outpatient service means， which can provide patients with immediate and personalized medication education and improve the quality of pharmaceutical care. However， it is also necessary to face the lag of database update and the lack of risk management， as well as the lack of diversification of medication education lists.

Objective To analyze the occurrence status and influencing factors of esophageal stenosis after surgery for early esophageal cancer. Methods A total of 285 patients with early esophageal cancer with endoscopic submucosal dissection (ESD) in the hospital from January 2019 to January 2021 were selected as research objects, and they were divided into control group with 237 cases (without esophageal stenosis) and study group with 48 cases (with esophageal stenosis) according to the occurrence of esophageal stenosis after surgery. The operation time, intraoperative blood loss and quality of life were compared between the two groups. The influencing factors of esophageal stenosis were analyzed. Results Compared with the control group, the study group had longer operation time, more intraoperative blood loss, and lower scores in psychological, environmental, physiological and social dimensions, and the between-group differences were statistically significant (P<0.05). Univariate analysis showed that esophageal stenosis after ESD had no correlations with gender, clinical stage, pathological type, history of drinking, the American Society of Anesthesiologists (ASA) classification, and anesthesia method (P>0.05). Patients aged ≥60 years old, damage of the muscularis propria, circumferential extent of lesion >3/4, malnutrition, tissue infiltration depth of M3+SM1, and longitudinal length of lesion >40 mm had a higher incidence of esophageal stenosis (P<0.05). Multivariate Logistics regression analysis showed that malnutrition, age ≥60 years, circumferential extent of lesion >3/4, damage of the muscularis propria, tissue infiltration depth of M3+SM1, and longitudinal length of lesion >40 mm were the main influencing factors for esophageal stenosis after ESD (P<0.05). Conclusion The occurrence of esophageal stenosis after ESD in patients with early esophageal cancer is related to factors such as damage of the muscularis propria, malnutrition, age ≥60 years, tissue infiltration depth of M3+SM1, circumferential extent of lesion >3/4, and longitudinal length of lesion >40 mm. Based on these factors, early prevention and control can be carried out to reduce the incidence of esophageal stenosis after surgery.

ObjectiveTo investigate the protective mechanism of Qianyang Yuyin granules （QYYY） on aldosterone-induced podocyte injury. MethodA total of 30 C57BL/6J mice were randomly divided into five groups： control group， model group， QYYY low dose （QYYY-L） group， QYYY high dose （QYYY-H） group， and spironolactone （SPL） group， with six mice in each group. Except for the control group， mice were implanted with osmotic minipumps and injected continuously with aldosterone （300 μg·kg^-1·d^-1） to induce renal injury. The drug administration group was given low and high doses （2.6， 5.2 g·kg^-1·d^-1） of QYYY and SPL （18 mg·kg^-1·d^-1） for 28 days. The renal pathological changes of mice were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression levels of Nephrin， Desmin， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cleaved Caspase-3， nuclear receptor subfamily 3 group C member 2 （NR3C2）， extracellular regulated protein kinases （ERK）， and phospho-ERK （p-ERK） in kidney tissue were detected by Western blot. The apoptosis levels of kidney tissue were detected by TdT-mediated dUTP nick and labeling （TUNEL） staining， and the superoxide dismutase （SOD） levels were detected. In vitro， the mice were divided into five groups： Control group， model group （aldosterone concentration of 200 nmol·L^-1）， QYYY-L group， QYYY medium dose （QYYY-M） group， and QYYY-H group （25， 50， and 100 mg·L^-1）. The effect of different concentrations of QYYY on the relative viability of aldosterone-induced podocytes was detected by cell proliferation and viability assay （CCK-8）. The expressions of Nephrin， Desmin， Bax， Bcl-2， cleaved Caspase-3， NR3C2， and p-ERK/ERK were detected by Western blot. AnnexinV-FITC/PI flow cytometry was used to detect the apoptosis levels of podocytes. Reactive oxygen species （ROS） in podocytes were observed by DCFH-DA. ResultCompared with the control group， the model group showed structural pathological changes and fibrotic conditions in the kidney， increased apoptosis levels （P<0.01）， and decreased SOD levels （P<0.01）. Aldosterone concentration at 200 nmol·L^-1 showed a significant decrease in podocyte activity （P<0.05）. Podocytes in the model group showed structural pathological changes， disordered arrangement of intercellular microfilaments， increased apoptosis levels （P<0.01）， and increased intracellular ROS levels （P<0.01）. The protein expressions of Nephrin， Bcl-2， and p-ERK/ERK in kidney tissue and podocytes were decreased （P<0.05， P<0.01）. The protein expressions of Desmin， Bax， cleaved Caspase-3， and NR3C2 were increased （P<0.05， P<0.01）. Compared with the model group， QYYY alleviated the structural damage and fibrosis of the kidney， decreased the apoptosis levels （P<0.05， P<0.01）， and enhanced the SOD content of the kidney （P<0.05， P<0.01）. QYYY improved the activity of podocytes （P<0.05， P<0.01）， restored the foot process structure of podocytes， and decreased apoptosis levels （P<0.01） and ROS levels of podocytes （P<0.01）. The protein expressions of Nephrin， Bcl-2， and p-ERK/ERK in kidney tissue and podocytes were increased （P<0.05， P<0.01）， and the protein expressions of Desmin， Bax， cleaved Caspase-3， and NR3C2 were down-regulated （P<0.05， P<0.01）. ConclusionQYYY improves aldosterone-induced podocyte injury by regulating the NR3C2/ROS/ERK pathway.

Objective To study clinical efficacy of ganciclovir in the therapy of infectious mononucleosis in adults.Methods 66 adults with infectious mononucleosis in a hospital from January 2010 to December 2014 were studied retrospectively,according to drug therapy,patients were divided into ganciclovir therapy group(n=31)and symptomatic therapy group(n=35),clinical features before therapy,therapeutic efficacy,and Epstein-Barr virus(EBV)DNA negative conversion time were analyzed.Results The time of defervescence,sore throat improvement,EBV-DNA negative conversion,subside of enlarged lymph node,and transaminase recovery in ganciclovir therapy group were all shorter than symptomatic therapy group(all P<0.05).Blood routine recovery time between two groups was not significantly different(P>0.05).Conclusion Ganciclovir has a good antiviral effect on the therapy of adult infectious mononucleosis,it can rapidly relieve patients from clinical symptoms including fever,sore throat and so on.

As a member of the sirtuins family, also called Class III histone deacetylases (HDACs), SIRT6 has many catalytic enzyme activities and plays a pivotal role in biological processes including anti-aging, chromatin regulation, transcriptional control, glucose and lipid metabolism, and DNA damage repair. Recently, increasing evidences indicated that SIRT6 was related to initiation and development of tumors, such as hepatic cancer, lung cancer, breast cancer and genital system tumors. However, SIRT6 might play a dual role in tumorigenesis and progression. SIRT6 often acted as a tumor suppressor, but might play an oncogenic role. Based on our current study, we depicted the essential roles of SIRT6 in the initiation and progression of various tumors, and summarized its mode of actions, which might provide clues for cancer therapy.
Carcinogenesis ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Neoplasms ; genetics ; pathology ; Oncogenes ; Sirtuins ; genetics ; metabolism

OBJECTIVETo investigate the correlation between CT image presentations and biochemical indexes in adrenal adenomas and pheochromocytomas.

METHODSWe retrospectively analyzed the CT features, cortisol rhythm, supine and orthostatic hypertension and 24-h urine methoxy in 209 patients with benign adrenal tumors. The relationship between CT findings and the biochemical indexes were analyzed in patients with different benign adrenal tumors.

RESULTSThe 209 cases analyzed included 53 cases of cortisol adenoma, 65 cases of aldosterone adenoma, 45 cases of non-functional adenoma and 46 cases of pheochromocytomas. The plain CT scan values of the 4 groups were 17.25 ± 1.81, 14.52 ± 1.57, 12.20 ± 2.05, 42.42 ± 0.97 HU, enhanced CT values (arterial phase) were 47.82 ± 3.07, 39.23 ± 2.37, 45.35 ± 6.46, and 104.93 ± 5.84 HU, respectively, and the differences between CT scan and enhanced CT values were 30.58 ± 2.29, 24.71 ± 1.55, 33.15 ± 5.18, and 62.51 ± 5.73 HU, respectively. In cortisol adenoma group, cortisol levels measured at 16:00 and 24:00 were positively correlated with plain CT scan value (r=0.506, P=0.0001; r=0.504, P=0.0001) and enhanced CT value (r=0.514, P=0.0001; r=0.554, P=0.0001). In pheochromocytoma group, plain scan CT value and the difference between plain and enhanced CT scan value were correlated with 24-h urine methoxy adrenaline (Rho;=0.342, 0.350; P=0.020, 0.017, respectively) and norepinephrine (Rho;=0.419, 0.412; P=0.004, 0.004, respectively).

CONCLUSIONPlain and enhanced CT scan values and their combination have important value in differential diagnosis of adenoma and pheochromocytoma tumor, CT values combine with biochemical indexes can reduce misdiagnosis and missed diagnosis of pheochromocytoma.

Adenoma ; chemistry ; diagnosis ; Adrenal Gland Neoplasms ; chemistry ; diagnosis ; Diagnosis, Differential ; Diagnostic Errors ; Humans ; Hydrocortisone ; Hypertension ; Pheochromocytoma ; chemistry ; diagnosis ; Retrospective Studies ; Tomography, X-Ray Computed

Objective To investigate the correlation between CT image presentations and biochemical indexes in adrenal adenomas and pheochromocytomas. Methods We retrospectively analyzed the CT features, cortisol rhythm, supine and orthostatic hypertension and 24-h urine methoxy in 209 patients with benign adrenal tumors. The relationship between CT findings and the biochemical indexes were analyzed in patients with different benign adrenal tumors. Results The 209 cases analyzed included 53 cases of cortisol adenoma, 65 cases of aldosterone adenoma, 45 cases of non-functional adenoma and 46 cases of pheochromocytomas. The plain CT scan values of the 4 groups were 17.25±1.81, 14.52±1.57, 12.20±2.05, 42.42±0.97 HU, enhanced CT values (arterial phase) were 47.82 ± 3.07, 39.23 ± 2.37, 45.35 ± 6.46, and 104.93 ± 5.84 HU, respectively, and the differences between CT scan and enhanced CT values were 30.58±2.29, 24.71±1.55, 33.15±5.18, and 62.51±5.73 HU, respectively. In cortisol adenoma group, cortisol levels measured at 16:00 and 24:00 were positively correlated with plain CT scan value (r=0.506, P=0.0001;r=0.504, P=0.0001) and enhanced CT value (r=0.514, P=0.0001;r=0.554, P=0.0001). In pheochromocytoma group, plain scan CT value and the difference between plain and enhanced CT scan value were correlated with 24-h urine methoxy adrenaline (ρ=0.342, 0.350; P=0.020, 0.017, respectively) and norepinephrine (ρ=0.419, 0.412; P=0.004, 0.004, respectively). Conclusion Plain and enhanced CT scan values and their combination have important value in differential diagnosis of adenoma and pheochromocytoma tumor, CT values combine with biochemical indexes can reduce misdiagnosis and missed diagnosis of pheochromocytoma.

Objective To investigate the correlation between CT image presentations and biochemical indexes in adrenal adenomas and pheochromocytomas. Methods We retrospectively analyzed the CT features, cortisol rhythm, supine and orthostatic hypertension and 24-h urine methoxy in 209 patients with benign adrenal tumors. The relationship between CT findings and the biochemical indexes were analyzed in patients with different benign adrenal tumors. Results The 209 cases analyzed included 53 cases of cortisol adenoma, 65 cases of aldosterone adenoma, 45 cases of non-functional adenoma and 46 cases of pheochromocytomas. The plain CT scan values of the 4 groups were 17.25±1.81, 14.52±1.57, 12.20±2.05, 42.42±0.97 HU, enhanced CT values (arterial phase) were 47.82 ± 3.07, 39.23 ± 2.37, 45.35 ± 6.46, and 104.93 ± 5.84 HU, respectively, and the differences between CT scan and enhanced CT values were 30.58±2.29, 24.71±1.55, 33.15±5.18, and 62.51±5.73 HU, respectively. In cortisol adenoma group, cortisol levels measured at 16:00 and 24:00 were positively correlated with plain CT scan value (r=0.506, P=0.0001;r=0.504, P=0.0001) and enhanced CT value (r=0.514, P=0.0001;r=0.554, P=0.0001). In pheochromocytoma group, plain scan CT value and the difference between plain and enhanced CT scan value were correlated with 24-h urine methoxy adrenaline (ρ=0.342, 0.350; P=0.020, 0.017, respectively) and norepinephrine (ρ=0.419, 0.412; P=0.004, 0.004, respectively). Conclusion Plain and enhanced CT scan values and their combination have important value in differential diagnosis of adenoma and pheochromocytoma tumor, CT values combine with biochemical indexes can reduce misdiagnosis and missed diagnosis of pheochromocytoma.