Pharmacogenomics(PGx)is a science based on functional genomics and molecular phar-macology,which has been rapidly developed and gradually applied to clinical practice in recent years.Therefore,China and the United States are committed to promoting the development of PGx education.This paper reviews PGx education in Chi-na and the United States,clarifies the significance of developing PGx education,and provides a de-tailed introduction to the current development sta-tus and challenges of PGx education in universities and clinical settings.Additionally,this paper makes some recommendations for developing PGx educa-tion and discusses future development trends in both countries.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective:To explore the selection criteria of the donor for islet transplantation of Chinese people by analyzing the correlation between pancreas characteristics and success rate of islets isolation.Methods:Data from 113 cases of human islet isolation were collected. According to the result of islet isolation, the donors were divided into two groups, the success group(IEQ≥250 000, purification≥30%, and viability≥80%), and the failure group(IEQ<250 000, or purification<30%, or viability<80%). The modified Ricordi method was used to digest pancreas tissue, and the continuous density gradient method was performed to purify islets. The islets were identified by staining with the Dithizone(DTZ), the islets were analyzed for cell viability and purity.Results:The donor age in success group was significantly younger than failure group in the range of age eligible for this study( t=2.479, P=0.015). Pearson correlation showed that donor age was positively corelated with islet yield( r=-0.214, P=0.047). There was more fat on the pancreas surface in the successful islet isolation group( z=-2.007, P=0.045). The digestibility( t=2.133, P=0.035) and recovery rate( t=5.912, P=0.001) were elevated in success group. Conclusion:The pancreases from younger donors could obtain the higher-yielding islet, the pancreas with more surface fat or with higher weight was associated with islet isolation success in the scope covered by the inclusion criteria of this study.

Objective:To investigate the correlations of β cell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods:Immunofluorescence staining with insulin and β cell dedifferentiated marker ALDH1A3 was used to evaluate the β cell dedifferentiation levels in 38 non-diabetic and 23 T2DM. Correlation analyses were performed between β cell dedifferentiation levels and available clinical parameters including age, body mass index, HbA 1C level, triglycerides, and cholesterol levels in non-diabetic subjects. Results:β cell dedifferentiation level defined by the positive expression of ALDH1A3 in β cells(ALDH1A3 + INS + cell proportion) was significantly elevated in T2DM subjects( P<0.001). In PreD subjects, ALDH1A3 + INS + cells proportion were decreased( P=0.050) and negatively correlated with HbA 1C( r=-0.44, P=0.006), but not with age and body mass index. The analysis of correlation with lipidemic parameters showed that ALDH1A3 + INS + cells proportion was positively correlated with plasma total cholesterol level( r=0.39, P=0.045), but not plasma total triglyceride. Conclusion:ALDH1A3 + INS + cells were found to be decreased in prediabetes, suggesting that there may be enhanced β-cell identity in prediabetes to compensate for insulin secretion requirements; ALDH1A3 + INS + cells were elevated in people with high plasma total cholesterol levels, suggesting that total cholesterol may be one of the factors that induce β-cell dedifferentiation.

Objective:To investigate the techniques used in blood flow control of Kimura laparoscopic spleen-preserving pancreatectomy (LSPDP).Methods:Forty·five patients with benign or low-grade malignant pancreatic diseases undergoing LSPDP at Huzhou Central Hospital from May 2014 to Oct 2021 were analyzed retrospectively. Patients were divided into splenic vascular flow control group ( n=22) and routine management group ( n=23). Results:There was no significant difference in gender, age, BMI, accompanying symptoms, hypertension, diabetes, lesion size and pathological diagnosis between the two groups (all P>0.05). A higher overall spleen preservation rate (90.9% vs. 52.2%, χ2=8.213, P=0.004), lower incidence of morbidity with Clavien grade ≥ Ⅱ (22.7% vs. 73.9%, χ2=9.911, P=0.002) and shorter postoperative hospital stay [(9.6±4.5) d vs. (14.3±6.6) d, t=2.447, P=0.008] were achieved in the vascular flow control group compared with those in the routine group. Conclusion:Splenic vascular flow control techniques improve the success rate of spleen preservation in laparoscopic distal pancreatectomy, reduce the postoperative complications and shorten the postoperative hospital stay.

Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors of the digestive system in the clinic. In recent years, the proposal and development of immunotherapy have set off a worldwide anticancer upsurge. In particular, programmed death receptor 1(PD-1) and programmed death receptor ligand 1(PD-L1) inhibitor have been used in a wide variety of tumor diseases and achieved good curative effect. However, the application of PD-1 or PD-L1 inhibitors in HCC is mostly still at the stage of clinical trials, and some clinical trials have shown gratifying results in patients with advanced HCC and postoperative recurrence. More studies have shown that PD-1 or PD-L1 inhibitors combined with radiofrequency, chemoradiotherapy, and molecular targeted drugs can bring greater benefits to patients.

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors of the digestive system in the clinic. In recent years, the proposal and development of immunotherapy have set off a worldwide anticancer upsurge. In particular, programmed death receptor 1(PD-1) and programmed death receptor ligand 1(PD-L1) inhibitor have been used in a wide variety of tumor diseases and achieved good curative effect. However, the application of PD-1 or PD-L1 inhibitors in HCC is mostly still at the stage of clinical trials, and some clinical trials have shown gratifying results in patients with advanced HCC and postoperative recurrence. More studies have shown that PD-1 or PD-L1 inhibitors combined with radiofrequency, chemoradiotherapy, and molecular targeted drugs can bring greater benefits to patients.

Surgical minimally invasive techniques such as image intervention, laparoscopy, endoscopy, and assisted medical robotics have become the mainstream of minimally invasive surgery (MIS). However, the vague concept, diverse misunderstanding, and the lack of standards have led to a lot of malpractice in current MIS. Based on the analysis of the clinical situation and the domestic and foreign literatures, the authors have put forward the theory of comprehensive minimally invasive surgery (CMIS), and established the concepts of minimally invasive prevention, minimally invasive diagnosis and minimally invasive follow-up in the view of hepatobiliary surgery. The authors have proposed "three-All" principles of all personnel, all aspects and all processes, and established a comprehensive four-level criteria of outcomes, complications, time and costs for CMIS, in an attempt to provide feasible and practical concepts and standards for MIS from a clinical practice and theoretical level, with a view to standardizing minimally invasive procedures and solving the problem of MIS.

Objective: To investigate the effects of free mini-flap on tibial side of third toe on repairing skin and soft tissue defect of finger pulp at the end of finger. Methods: From August 2013 to May 2017, 18 patients with skin and soft tissue defect of finger pulp at the end of finger were admitted to our unit, with 12 men and 6 women aged 16 to 54 years. As the skin and soft tissue defect sites, there were 3 cases of thumb, 8 cases of index finger, 4 cases of middle finger, and 3 cases of ring finger. The area of defects ranged from 2.0 cm×1.4 cm to 3.5 cm×2.4 cm. Free mini-flaps on tibial side of third toes were designed according to area and shape of defects, and the length and width of flaps were 0.1 to 0.2 cm longer than the length and width of the defects, respectively. The area of flaps ranged from 2.1 cm×1.5 cm to 3.7 cm×2.6 cm. The end-to-end anastomosis of subcutaneous veins of flaps and superficial veins of the finger-palm side or superficial dorsal digital vein, the end-to-end tension-free anastomosis of the base metatarsal arteries on tibial side of third toe and proper digital arteries of recipient finger were performed. Besides, anastomosis of base metatarsal nerve on tibial side of third toe and proper digital nerve of recipient finger was performed. The donor sites on feet were sutured directly or repaired with full-thickness skin grafts on medial upper leg of the same side. The survival of flaps after operation and the follow-up of patients were observed. Results: All flaps survived well, with good blood supply. Among the 18 patients, 2 patients lost to follow-up, and 16 patients were followed up for 4 to 36 months. The shape and texture of flaps were good. After reconstruction, finger pulps at the end of finger were plump, with fingerprint. Function of the finger restored well, and the two-point discriminatory distances of flaps were 5 to 10 mm. The donor sites on feet of 14 patients healed after the operation, the other 2 patients had necrosis on edge and central area of skin grafts, and the necrotic area healed after dressing change. The skin graft areas on feet were wear-resistant, with slight damage to donor sites and did not influence shoes wearing and walking. Besides, patients did not feel uncomfortable. Conclusions Skin and soft tissue defects of finger pulp at the end of finger repaired by free mini-flaps on tibial side of third toe are with good shape and slight damage to donor sites, and the operation is simple. It is worthy of popularization and application in clinic.