Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Purpose To explore the value of the new generation tau PET tracer 18F-Florzolotau in Alzheimer's disease(AD)at different stages.Materials and Methods Twenty-five MCI patients and sixty-one AD patients with positive β-amyloid status in Huashan Hospital,Fudan University from February 2020 to January 2022 were retrospectively enrolled with 18F-Florzolotau PET imaging and demographic and clinical data.The pre-processed PET images were analyzed by SPM two-sample t-test between MCI and AD groups,and the standardized uptake value ratios(SUVR)were extracted from the region of interest defined by SPM analysis(P＜0.001);scaled subprofile model/principal component analysis was used to construct the different tau related patterns(MCItauRP,ADtauRP)and calculate the corresponding expression values.The classification efficiency of SUVR and MCItauRP,ADtauRP expression values was evaluated by receiver operating characteristic curve.Results Compared with MCI patients,tau protein deposition of AD patients was increased mainly in the bilateral temporal,occipital lobe(P＜0.001),and the SUVR of these brain region in the AD group was higher than that in the MCI group(Z=-3.164,P＜0.00l);the expression values of MCItauRP and ADtauRP were significantly different between the AD group and MCI group(t=3.72,Z=-3.51;both P＜0.001),and these expression values of AD patients were higher than those in the MCI group;the accuracy of tauRP expression values and SUVR for the differentiation between the AD and MCI group were 61.63％,65.12％and 65.12％,respectively;the sensitivity was 88.00％,96.00％and 100.00％,respectively;the specificity was 50.82％,52.46％and 50.82％,respectively.Conclusion The new tau PET can identify and distinguish the differences in tau protein deposition between AD and MCI patients.However,the classification and diagnosis efficiency is not high.In the future,it is necessary to find a more ideal analysis method.

Despite quitting smoking, patients with acute coronary syndrome (ACS) still have an increased risk of cardiovascular events. Clonal hematopoiesis of indeterminate potential (CHIP), which may be induced by smoking, has been identified to be associated with the development of coronary artery disease. However, it is unclear whether CHIP has a detrimental effect on the poor prognosis of ACS patients even after smoking cessation. This single-center, prospective cohort study will recruit 1,029 ACS patients undergoing complete percutaneous coronary intervention. The enrolled patients will be categorized into 3 groups based on their smoking status at admission: current smoker, non-smoker, and previous smoker. Previous smokers are defined as patients who have quit smoking for at least 1 year before experiencing the index ACS event. Whole-exome sequencing will be performed to identify the occurrence of CHIP in each patient. The primary endpoint is major adverse cardiovascular and cerebrovascular events, defined as a composite of cardiac death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and ischemic stroke. The association between CHIP and the primary endpoint will be determined by using Cox proportional hazard regression. This study aims to investigate the association among smoking cessation, CHIP, and the prognosis of ACS patients to provide new insights into the impact of CHIP on ACS patients, particularly among those who have quit smoking. The results will be published following the STROBE in a peer-reviewed scientific journal (Trial registration number: NCT04987268).

Despite quitting smoking, patients with acute coronary syndrome (ACS) still have an increased risk of cardiovascular events. Clonal hematopoiesis of indeterminate potential (CHIP), which may be induced by smoking, has been identified to be associated with the development of coronary artery disease. However, it is unclear whether CHIP has a detrimental effect on the poor prognosis of ACS patients even after smoking cessation. This single-center, prospective cohort study will recruit 1,029 ACS patients undergoing complete percutaneous coronary intervention. The enrolled patients will be categorized into 3 groups based on their smoking status at admission: current smoker, non-smoker, and previous smoker. Previous smokers are defined as patients who have quit smoking for at least 1 year before experiencing the index ACS event. Whole-exome sequencing will be performed to identify the occurrence of CHIP in each patient. The primary endpoint is major adverse cardiovascular and cerebrovascular events, defined as a composite of cardiac death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and ischemic stroke. The association between CHIP and the primary endpoint will be determined by using Cox proportional hazard regression. This study aims to investigate the association among smoking cessation, CHIP, and the prognosis of ACS patients to provide new insights into the impact of CHIP on ACS patients, particularly among those who have quit smoking. The results will be published following the STROBE in a peer-reviewed scientific journal (Trial registration number: NCT04987268).

Multi-centre clinical trials on PET/CT brain imaging are complex to organize and require careful co-ordination and management. This article describes considerations, which are necessary when designing and starting a multi-centre clinical trial on PET/CT brain imaging, based on guidelines and multi-center clinical brain imaging studies, providing references for further studies.

Objective To explore the function and survival of islet grafts during co-transplantation with adipose mesenchymal stem cells (AMSCs) in diabetic mice .Methods After human AMSCs and islet cells were isolated ,purified and then subcutaneously co-transplanted into nude mice with diabetes mellitus . Four groups of AMSCs + islet co-transplantation , islet transplantation alone ,phosphate buffered solution (PBS) and normal control mice were designated . Islet cell activity and apoptosis/revascularization degree of islet grafts were observed by immunohistochemical double staining of insulin ,factor associated suicide (Fas) and CD31 antibody . The blood glucose and serum insulin levels of mice and the survival time of islet grafts were compared . Results The blood glucose and serum insulin levels of diabetic mice analyzed by multivariate analysis in AMSCs + islet co-transplantation group were better than those in islet transplantation alone group (P< 0 .05 ) . The mean survival time (MST ) of islet grafts was longer in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(81 .33 ± 7 .58) vs .(58 .17 ± 6 .91) days] (P<0 .05) .At Day 7 post-transplantation ,insulin staining intensity of islet grafts was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group while Fas staining intensity of islet grafts was lower .And mean microvascular density (MVD) of islet grafts per square millimeter was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(21 .8 ± 5 .6 ) vs . (14 .6 ± 4 .1 )] ( P< 0 .05 ) .Conclusions Co-transplantation with AMSCs may improve the function of islet grafts ,prolong its survival and promote its revascularization .

Objective To investigate the revascular and transplanted effects of islet grafts after co-transplantation with vascular endothelial cells ( ECs) in diabetic rats. Methods The rat ECs and islet cells were isolated and purified, then subcutaneously co-transplanted to the inbred SD male rats with diabetes mellitus, the group of islets transplanted alone, group of phosphate buffered solution, and group of normal rats served as control. Islet grafts revascularization degree, islet cells activity and apoptosis were observed by immunohistochemical double staining of CD31, insulin and factor associated suicide (Fas) antibody. The results of intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT), the blood glucose and insulin levels of the rats and the survival time of the islet grafts were compared. Results The blood glucose concentrations of IPGTT and IPITT, the blood glucose and insulin levels of rats analyzed by multivariate analysis in the ECs and islets transplantation group were better than those in the islets transplantation alone group (P<0.05). The islet grafts mean survival time of the ECs and islets transplantation group was longer than that of the islets transplantation alone group (P<0.05). On the 7th day after transplantation, mean microvascular density of islet grafts per square millimeter in the ECs and islets transplantation group was 26.4 ± 6.1, significantly greater than that in the islets transplantation alone group 18.3 ± 5.7 (P<0.05). In the ECs and islets transplantation group, insulin staining intensity was higher than that in the islets transplantation alone group (P<0.05), while factor associated suicide(Fas) staining intensity was lower than that in the islets transplantation alone group ( P<0. 05 ). Conclusion Co-transplantation with ECs could promote the revascularization of islet grafts and improve the effect of islet transplantation.

Objective To investigate the influence of VEGF165 gene transfection on the revascularization and transplantation effect of islet grafts.Methods The rat islet cells were transfected with lentivirus containing VEGF165 gene (LV-VEGF165) in vitro,then transplanted to the renal capsule of inbred SD male rats with diabetes mellitus.Islet cells transfected with lentivirus marked with AcGFP1 and no VEGF165 gene were set as null vector control group (LV-AcGFP1 group),individual islet cells as blank control group.VEGF165 expression in vivo and in vitro was detected by ELISA.The islet grafts revascularization degree and islet cell activity were observed by immunohistochemical double staining of insulin and CD31 antibody.Blood glucose and insulin level of rats with diabetes mellitus and survival time of islet grafts were compared.Results The VEGF165 concentrations in the LV-VEGF165 group secreted by islet cells in vivo and in vitro were significantly higher than those in the LV-AcGFP1 group and the blank control group (P＜0.01).Mean microvascular density (MVD) of islet grafts per square millimeter in the LV-VEGF165 group was (24.3 ± 3.7),significantly greater than that in the LV-AcGFP1 group (12.4 ± 2.5) and the blank control group (12.4 ± 2.5) (P＜ 0.01).Insulin staining intensity in the LV-VEGF165 group was also higher than that in the LVAcGFP1 group and the blank control group.The blood glucose and insulin levels in rats with diabetes mellitus analyzed by multivariate analysis in the LV-VEGF165 group were controlled more effectively than those in the LV-AcGFP1 group and the blank control group (P＜0.01).The islet grafts mean survival time (MST) after transplantation in the LV-VEGF165 group was longer than that of the LVAcGFP1 group and the blank control group (P＜0).01).Conclusion The VEGF165 gene transfection to islet cells could promote the revascularization of islet grafts and improve the effect of islet transplantation.

A 77-year-old female patient underwent a laparoscopic left radical nephrectomy for renal malignant neoplasm.She received an IV infusion of cefoperazone sodium and tazobactam sodium 2 g about 30 minutes before surgery and an IV infusion of hydrocortisone injection 400 mg during the operation.On the 2nd day after surgery,intravenous infusion of cefoperazone sodium and tazobactam sodium (2 g twice daily) and hydrocortisone injection (200 mg once daily) were given sequentially.On the 3rd day after operation,about 30 min after completion of the IV infusion of hydrocortisone injection,the patient's blood pressure dropped suddenly to 84/48 mmHg,her heart rate was 150 beats per minute,and clouding of consciousness,lethargy,generalized flush and sweating appeared.Adrenal crisis was considered.Dexamethasone,hydrocortisone,dopamine,epinephrine,and etc.were successively given to rescue her.About 30 minutes later,the patient's symptoms improved slightly and then the patient was immediately transferred to ICU.In ICU,cefoperazone sodium and tazobactam sodium was continued according to the original scheme,hydrocortisone injection was changed to 150 mg twice daily,and the 2 groups of drugs were infused at 2-hour intervals.At the same time,dopamine 360 mg dissolved in 50 ml of 0.9％ sodium chloride injection was administered intravenously via an infusion pump.The patient's condition improved.On the 7th day after operation,the 2 groups of drugs were intravenously infused sequentially again and the similar symptoms appeared again.The pharmacist considered that the disulfiram-like reactions was caused by the combined use of cefoperazone sodium and tazobactam sodium and hydrocortisone injection and suggested that the two drugs should be discontinued.After the drugs withdrawal,no similar symptoms recurred.