Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To observe the value of radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced hepatobiliary phase(HBP)MRI for assessing clinical pathological stage of hepatic fibrosis(HF).Methods Data of 240 patients with pathologically/clinically diagnosed and clinical pathological staged HF who underwent Gd-EOB-DTPA enhanced MR examination were retrospectively analyzed.The liver-to-muscle signal intensity ratio(SIR1)and liver-to-spleen signal intensity ratio(SIR2)were measured based on HBP images.Radiomics features of HBP images were extracted and screened to construct radiomics models.The signal intensity ratio(SIR)-radiomics combined models were constructed based on SIR and radiomics signatures.Receiver operating characteristic(ROC)curves were drawn to evaluate the efficacy of each model for assessing clinical pathological stage of HF.Results The area under the curve(AUC)of SIR1 and SIR2 models for assessing clinical pathological stage of HF were 0.63-0.70 and 0.65-0.71,respectively.The most effective radiomics model for assessing HF,significant HF,advanced HF and early cirrhosis was support vector machine(SVM),SVM,light gradient boosting machine and K-nearest neighbor model,respectively,with the AUC in validation set of 0.87,0.82,0.81 and 0.80,respectively,while the AUC of SIR-radiomics combined models in validation set of 0.88,0.82,0.82 and 0.81,respectively.Conclusion The radiomics models based on Gd-EOB-DTPA enhanced HBP MRI were helpful for assessing clinical pathological stage of HF.Combining with HBP SIR could improve their efficacy.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

A Clinical pharmacist was fully involved in the anticoagulation drug treatment management process of a 104-year-old patient with a large area of cerebral infarction combined with chronic kidney disease stage Ⅴ and secondary deep vein thrombosis.After the patient was diagnosed with deep vein thrombosis,the clinical pharmacist comprehensively analyzed the patient's super-advanced age,history of atrial fibrillation,large area of cerebral infarction,extremely poor kidney function,deep vein thrombosis,and high bleeding risk indicated by the HAS-BLED score.They worked with the clinical doctor to develop an individualized anticoagulation treatment strategy for the patient.At the beginning of the treatment,warfarin was given to the patient at a daily dose of 1.25 mg,and the patient's coagulation indicators and kidney function were dynamically rechecked.The patient's blood creatinine level did not show significant changes throughout the anticoagulation treatment process.On the 8th day of medication,the patient's INR was 2.47,and the clinical pharmacist suggested adjusting the Warfarin to an alternate-day dose of 1.25 mg and 0.625 mg.Subsequently,the patient's INR was 2.41,and the condition improved,leading to discharge.Throughout the anticoagulation drug management process,the clinical pharmacist participated in the clinical decision-making for anticoagulant drug selection,provided professional medication guidance,and pharmacological monitoring to ensure the safe clinical use of drugs for special populations.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Immmunosuppressants are mainly used to reduce rejection after solid organ transplantation,so as to improve the success rate of organ transplantation.However,long-term use of immunosuppressants can also serious-ly impair the immune function of patients,thereby increasing the risk of viral infection and postoperative complica-tions,leading to transplant failure.Therefore,patients need to use both immunosuppressants and antiviral agents.If some immunosuppressants with antiviral effects are found,the patient's burden of taking medicines will be greatly reduced.Currently,the immunosuppressants with antiviral effect have been focused by researchers.The gradual re-vealing of the antiviral mechanism of these immunosuppressants will help to optimize the treatment plan of postope-rative rehabilitation of organ transplant recipients.Based on the mechanism of rejection of transplanted organ,this paper systematically describes the types of viruses which closely related to infection of organ transplant patients and the molecular mechanism of some immunosuppressants in antiviral aspects,which further provides a new idea for clinical prevention and treatment of viral infection due to organ transplantation.

Objective Evaluation of the clinical efficacy of f trochanteric flip osteotomy combined with Kocher-Langen-beck approach for high acetabular posterior wall fracture.Methods Between January 2020 and December 2022,20 patients with high acetabular posterior wall fractures were retrospectively analyzed,including 12 males and 8 females,aged 18 to 75 years old.They were divided into two groups according to the different surgical methods.Ten patients were treated with greater trochanteric osteotomy combined with Kocher-Langenbeck approach as the observation group,including 5 males and 5 fe-males,aged from 18 to 75 years old.Ten patients were treated with Kocher-Langenbeck approach alone as the control group,including 7 males and 3 females,aged from 18 to 71 years old.Matta reduction criteria were used to evaluate the reduction quality of the two groups,and Harris score was used to compare the hip function of the two groups at the latest follow-up.The operation time,blood loss and postoperative complications of the two groups were analyzed.Results All patients were followed up for 10 to 24 months.According to the Matta fracture reduction quality evaluation criteria,the observation group achieved anatomical reduction in 6 cases,satisfactory reduction in 3 cases,and unsatisfactory reduction in 1 case,while the control group only achieved anatomical reduction in 3 cases,satisfactory reduction in 3 cases,and unsatisfactory reduction in 4 cases.At the final follow-up,the Harris hip score ranged from 71.4 to 96.6 in the observation group and 65.3 to 94.5 in the control group.According to the results of Harris score.The hip joint function of the observation group was excellent in 6 cases,good in 3 cases,and fair in 1 case.The hip joint function of the control group was excellent in 2 cases,good in 3 cases,fair in 3 cases,and poor in 2 cases.In the observation group,the intraoperative blood loss ranged from 300 to 700 ml,and the operation dura-tion ranged from 120 to 180 min;in the control group,the intraoperative blood loss ranged from 300 to 650 ml,and the opera-tion duration ranged from 100 to 180 min.Complications in the observation group included 1 case of traumatic arthritis and 1 case of heterotopic ossification,while complications in the control group included 3 cases of traumatic arthritis,3 cases of het-erotopic ossification and 1 case of hip abduction weakness.Conclusions Trochanteric flip osteotomy combined with the Kocher-Langenbeck approach significantly improved anatomical fracture reduction rates,enhanced excellent and good hip joint function outcomes,and reduced surgical complication incidence compared to the Kocher-Langenbeck approach alone.Clinical application of this combined approach is promising,although larger studies are needed for further validation.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

ObjectiveTo explore the improvement effect of Flos Puerariae， Hoveniae Semen， and their compatibility on acute alcoholic gastric mucosal injury， and lay a foundation for further development of Flos Puerariae， Hoveniae Semen， and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. MethodThe acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor （15 mL·kg^-1）. A total of 120 male ICR mice were randomly divided into 8 groups， namely， the blank group， model group， omeprazole group （0.026 g·kg^-1）， Flos Puerariae-Hoveniae Semen （compatibility） high， medium， and low-dose groups （29.2，14.6， 7.3 g·kg^-1）， Flos Puerariae group （19.5 g·kg^-1）， and Hoveniae Semen group （19.5 g·kg^-1）， with 15 mice in each group. After one week of adaptive feeding， the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg^-1 for 3 d. From the 4^th day， after 1 h of administration， Erguotou liquid was administrated at the rate of 15 mL·kg^-1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration， the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph， and the activity of ethanol dehydrogenase （ADH） in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of nuclear transcription factor-κB （NF-κB） p65 and NF-κB inhibitory protein α （IκBα） were detected by real-time polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in serum of mice in the model group was increased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased （P<0.01）， and the mRNA expression of IκBα was decreased （P<0.01）. As compared with the model group， the drunkenness time of the omeprazole group， high and medium-dose compatibility groups， and Flos Puerariae group was prolonged （P<0.05）， the sober up time of the high and medium-dose compatibility groups was shortened （P<0.05）， the ethanol concentration in the serum of the high-dose compatibility group was decreased （P<0.05）， the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased （P<0.05）， the macroscopic injury score of the high， medium， and low-dose compatibility groups and Flos Puerariae group was decreased （P<0.05）， the score of pathological injury in the omeprazole group， high， medium， and low-dose compatibility groups， and Flos Puerariae group was decreased （P<0.01）， the expression of IL-6 in serum of all drug groups was decreased （P<0.05）， the expression of IL-1β in serum of the omeprazole group， high， medium， and low-dose Flos Puerariae groups， and Hoveniae Semen group was decreased （P<0.05）， the expression of TNF-α in serum of high and medium-dose groups was decreased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased （P<0.05）， and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high， medium， and low-dose compatibility groups was increased （P<0.05）. As compared with the high-dose compatibility group， the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened （P<0.01）， the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged （P<0.01）， the concentration of ethanol in the serum of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group increased （P<0.05）， the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased （P<0.05）， the pathological injury score of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， the content of IL-1β in serum of low-dose compatibility group， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased （P<0.05）. As compared with the medium-dose compatibility group， the drunkenness time in the Hoveniae Semen group was shortened （P<0.05）， the sober up time in the Flos Puerariae group was prolonged （P<0.05）， the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased （P<0.01）， and the content of IL-1β in serum of the low-dose compatibility group， the Flos Puerariae group， and Hoveniae Semen group was increased （P<0.05）. As compared with the low-dose compatibility group， the pathological injury score of the Hoveniae Semen group was increased （P<0.05）. ConclusionFlos Puerariae， Hoveniae Semen， and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice， which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa， and the high-dose compatibility group has the optimal effect.

Objective:To explore the prediction model of tissue chip technology for the chemotherapy response of patients with colorectal cancer.Methods:217 patients with colorectal cancer who had received standardized chemotherapy in the Affiliated People’s Hospital of Ningbo University from Jan. 2017 to Dec. 2019 were prospectively selected. The patients were randomly divided into training set (152 cases) and test set (65 cases) according to the ratio of 7:3, and were followed up for 6 months. The clinical data of the patients in the training set were compared, the expression levels of Ang-2, caspase-3 and CD147 in the patients were analyzed by tissue microarray technology, and the related factors affecting the responsiveness of colorectal cancer chemotherapy were analyzed by the Logistic regression model. R software was used based on the training set. A nomogram prediction model was built and model performance on the test set was evaluated.Results:One case was excluded from the training center, and 151 cases were finally included, including 93 cases in the chemotherapy response group and 58 cases in the chemotherapy response group. The tumor diameter, serum carcinoembryonic antigen, caspase3, Ang2 expression level, and the proportion of clinical stage IV in the poor chemotherapy group were significantly higher than those in the good chemotherapy group (all P<0.05) ; Logistic regression showed tumor diameter ( OR=2.394), serum carcinoembryonic antigen ( OR=1.878), caspase-3 ( OR=4.261), Ang-2 expression level ( OR=5.457), and clinical stage IV ( OR=5.954) were independent risk factors for adverse drug reactions in patients with colorectal cancer (all P<0.05). The consistency index (C-index) for predicting the factors related to adverse chemotherapy reactions in patients with colorectal cancer was 0.915. External verification showed that the sensitivity was 86.96%, the specificity was 92.50%, and the accuracy was 90.48% (42/65) . Conclusion:The expression levels of Ang-2 and caspase-3 are correlated with the responsiveness of colorectal cancer to chemotherapy, and can be used as predictive indicators to evaluate the responsiveness of colorectal cancer to chemotherapy.