OBJECTIVE To summarize the current status of position training for clinical pharmacists in China and provide references for the continuous optimization of such training programs. METHODS SinoMed， CNKI，VIP and Wanfang Data were electronically searched to collect position training of clinical pharmacists studies from the inception until November 5th 2024. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS & A total of 68 pieces of relevant literature were included in the study. Among them， 50 studies reported on training content， 49 involved the allocation of teaching resources in the bases， 48 addressed training methods， and 39 focused on training evaluation； only 2 studies mentioned faculty development. There were notable variations in the clinical pharmacist training programs across different bases， particularly in the allocation of teaching resources， such as the composition of the teaching team and the utilization of auxiliary teaching tools. Additionally， differences existed in training approaches， such as those employing a single method versus a blended approach. Conversely， the core training content of each base generally revolved around clinical pharmacy practice， demonstrating a degree of consistency. Moreover， the overall emphasis on teacher training and assessment tended to be obviously insufficient. Each base can focus on enhancing the competence of clinical pharmacists by allocating teaching resources， selecting training methods， improving training content， and using evaluation tools， to further enhance the quality of clinical pharmacist training.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Background Arsenic, cobalt, barium, and other individual metal exposure have been confirmed to be associated with the incidence of kidney stones. However, there are few studies on the association between mixed metal exposure and kidney stones, especially in occupational groups. Objective To investigate the association between mixed metal exposure and kidney stones in an occupational population from a metal smelting plant. Methods A questionnaire survey was conducted to collect sociodemographic characteristics, medical history, and lifestyle information of 1158 mixed metal-exposed workers in a metal smelting plant in Guangdong Province from July 2021 to January 2022. Midstream morning urine samples were collected from the workers, the concentrations of 18 metals including lithium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, cadmium, cesium, barium, tungsten, titanium, and lead were measured by inductively coupled plasma mass spectrometry, and the urinary mercury levels were measured by cold atomic absorption spectroscopy. Based on predetermined inclusion criteria, a total of 919 mixed metal-exposed workers were included in the study, including 117 workers in the kidney stone group and 802 workers in the non-kidney stone group. With a detection rate of urinary metals greater than 80% as entry criterion, 16 eligible metals were finally included for further analysis. Parametric or non-parametric methods were used to compare the differences between continuous or categorical variables of the non-kidney stone group and the kidney stone group. Logistic regression models were constructed to explore the association between individual metal exposures and kidney stones. Weighted quantile sum (WQS) regression models were used to evaluate the association between mixed metal exposure and kidney stones, as well as the weights of each metal on kidney stones. Then Bayesian kernel machine regression (BKMR) models were used to explore the overall effect of mixed metal exposure on renal calculi and the potential interactions between metals. Results We found that there were significant differences in sex, age, length of service, and body mass Index (BMI) between the non-kidney stone group and the kidney stone group (P<0.05). The urinary concentrations of molybdenum and barium in the kidney stone group were higher than those in the non-kidney stone group, and the differences were statistically significant (P<0.05). The logistic regression models demonstrated that urinary cobalt, arsenic, molybdenum, and barium were positively correlated with the risk of kidney stones (P_trend<0.05). The WQS regression models showed that the mixed exposure to vanadium, cobalt, arsenic, molybdenum, and barium was positively associated with the risk of kidney stones (P<0.05). Among them, molybdenum, arsenic, and barium accounted for 0.391, 0.337, and 0.154, respectively. The BKMR results revealed a positive association between metal mixture exposure and the risk of kidney stones (P<0.05). When other metals were fixed at the 25th, 50th, or 75th percentile, arsenic, molybdenum, cobalt, and barium exhibited significant positive effects on the risk of kidney stones (P<0.05), while vanadium showed a significant negative effect (P<0.05). The interaction analysis demonstrated interactions between barium and cobalt, as well as between vanadium and cobalt (P<0.05). Conclusion In the occupational population of this smelter, occupational mixed metal exposure could increase the risk of kidney stones, and the main metals are molybdenum, arsenic, barium, and cobalt.

Background Occupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. Objective To explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. Methods From January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. Results A total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P₅₀ (P₂₅, P₇₅) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g⁻¹, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (OR_int)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). Conclusion This study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.

Objective    To define the patient characteristics and perioperative management, and to define the mortality and its risk factors after arterial switch operation (ASO). Methods    We conducted a bidirectional cohort study with 571 consecutive patients undergoing ASO from 1997 to 2016 in our hospital. We enrolled patients who underwent ASO before 2012 retrospectively and after 2012 prospectively and followed up all the patients prospectively. Demographic characteristics, clinical information and mortality of these patients were summarized. Joinpoint regression analysis was used to identify the time trend of the overall mortality. Kaplan-Meier survival analysis was used to evaluate the mid- and long-term survival rate after ASO. Cox proportional hazards regression models were used to explore the potential factors associated with mortality. The cumulative incidence of complications after ASO was predicted using competing risk models. Results    Several aspects of patients’ characteristics and perioperative management in our center differed from those in the developed countries. The overall mortality and in-hospital mortality after ASO was 16.3% and 15.1%, respectively. The overall cumulative survival rate at 5, 10 and 15 years after ASO was 83.3%, 82.8% and 82.8%, respectively. A significant decrease of overall mortality from 1997 to 2016 was observed. Independent risk factors of mortality included earlier ASO (1997-2006), single or intramural coronary anatomy and longer cardiopulmonary bypass time. Ten years after ASO, re-intervention, arrhythmia, pulmonary and anastomotic stenosis were the most common complications with a cumulative incidence over 10%. Conclusion    Significant improvements in the results of the ASO were observed and the postoperative mortality rate is close to reports from developed countries. Nonetheless, we have identified the need for further improvement in the early and late postoperative periods after ASO. Pulmonary stenosis, anastomotic stenosis and arrhythmia should be paid attention to during the long-term follow-up after ASO.

To improve the accuracy of prenatal diagnosis for coarctation of the aorta ( CoA ) by comparatively analyzing the relevant factors and their application value . Methods Cases of disproportion of ventricles and great vessels were selected between January 2011 and July 2018 . Only liveborn fetuses with complete postnatal follow‐up were included in the study . One hundred and twelve cases were retrieved and analyzed . According to the postnatal ultrasound and CT results ,the patients were divided into gruop A and goup B . Different fetal echocardiography parameters and features were selected to evaluate the diagnostic value . Logistic regression analysis was used to select the best predictors of CoA and optimal cut‐offs for these parameters were identified by ROC analysis . Results One hundred and thirty eight fetuses were suspected to be CoA ,and 112 of them were born . T hey included 59 cases ( 52 .9% ) with CoA ( Group A ) and 53 cases ( 47 .3% ) without CoA ( Group B ) . T here were statistically significant differences between the two groups in gestational age ,Z‐score of diameter of left ventricle ,ascending aorta ( AAO ) and aortic arch isthmus ,main pulmonary artery ( M PA )/AAO diameters ratio ,and arterial duct/isthmus diameters ratio . T he parameters most predictive of postnatal CoA selected by logistic regression and the cut‐off values identified by ROC analysis were :gestational age at first diagnosis ≤34 .5 weeks ,Z‐score of diameter of left ventricle ＜ －1 .8 ,Z‐score of diameter of isthmus ＜ －2 .7 ,M PA/AAO diameters ratio＞1 .6 . AUC yielded by these parameters in combination was 0 .94 ( 95% CI :0 .89 －0 .99) . T he study group were divided into two subgroups by gestational age at first diagnosis .T he parameters and cut‐off values in subgroups were selected by the same analysis as above :Group Ⅰ ( ≤ 34 .5 weeks ) ,Z‐score of diameter of right ventricle ＞2 .1 ,M PA/AAO diameters ratio＞1 .6 ; Group Ⅱ( ＞34 .5 weeks) ,M PA/AAO diameters ratio ＞ 1 .7 ,arterial duct/isthmus diameters ratio ＞ 2 .3 . Meanw hile ,some ultrasound features ( including aortic arch hypoplasia ,retrograde blood flow of aortic isthmus ) should also be considered to improve diagnostic accuracy . Conclusions Combined with the use of different ultrasound parameters and features at different gestational weeks can improve the accuracy of the prenatal diagnosis of CoA in the right heart dominant fetus .

Objective To explore the effect of the surgical treatment in neonates with congenital heart disease(CHD) and the factors related to the perioperative mortality during cardiopulmonary bypass. Methods Totally,666 neonates undergo-ing CHD operation were reviewed in a single center from Jan 2006 to Dec 2014,of which,431 cases had complete cardiopul-monary bypass records. Analysis was performed to investigate the association between perioperative mortality and potential fac-tors,especially the cardiopulmonary bypass factors during different periods. In the multivariate Cox proportional hazard model, factors with statistical significance(P < 0. 1)in the univariate analysis were included in the model,such as,surgeon grouping, year of surgery,Aristotle score,preoperative weight,preoperative and intraoperative sodium bicarbonate volume and postopera-tive low cardiac output. Results The neonates enrolled ranged 8 - 22 days after birth,and 2. 7 - 3. 6 kg at weight. The mor-tality rate decreased from 23. 7％ in 2006 to 12. 4％ in 2014,showing a gradual decline(P = 0. 02). The mortalities of differ-ent CHDs were:pulmonary atresia(24. 4％),coarctation of the aorta( 16. 7％),transposition of the great arteries( 13. 1％), total anomalous pulmonary venous connection( 11. 0％),ventricular septal defect( 10. 6％),and so on. The volume of preop-erative and intraoperative 5％ sodium bicarbonate was 30(20 - 50)mL in death group,higher than that in survival group[23 ( 15 - 30)ml]. While the preoperative weight was 3. 1(2. 7 - 3. 5)kg,lower than that in survival group[3. 3(3. 0 - 3. 6) kg]. The total amount of Plasmalyte/ Ringer,erythrocytes,ultrafiltration volume and the cardiac assist ratio were higher in the death group than in the survival group. After controlling the confounding effect of surgeons,the multivariable Cox proportional hazard model showed that:the independent risk factors for perioperative mortality were pulmonary atresia[aHR = 3. 89( 1. 78 -8. 42)],5％ sodium bicarbonate volume ≥50 ml[aHR = 2. 62( 1. 14 - 6. 04)],erythrocytes volume > 200 ml[aHR = 2. 26 ( 1. 1 - 4. 06)]and postoperative low cardiac output[aHR = 6. 76(3. 30 - 13. 87)]. Conclusion During the study period, the preoperative mortality for neonates with CHD had a dramatical decrease,although the preoperative risk factors for the pa-tients increased. Pulmonary atresia repair surgery had the highest mortality in neonates. Factors associated with the periopera-tive mortality includedpreoperative acidosis and postoperative low cardiac output. There is a significant association between the improvement of perioperative mortality and the improvement of the technology of minimized cardiopulmonary bypass circuit dur-ing neonatal operation. It is suggested that the total erythrocytes volume maintains less than 200 ml.

Objective: To explore the relationship between overnight urinary sodium to potassium ratio and the risk of cardiovascular disease (CVD). Methods: A subsample of 10 percent of the participants (35-59 years old) from the People's Republic of China-United States Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology (prospective survey) were used. Three consecutive overnight urine samples were collected in the autumn of 1983-1984 and the spring in 1985-1986, respectively. Urinary sodium and potassium were detected and calculated for 8 hours excretion. The occurrences of cardiovascular events were recorded in 2 years interval from 1987-1988 until December 31, 2005. Participants were divided into first ratio group, second ratio group, and third ratio group based on the tertiles of sodium to potassium ratio. Cox proportional hazard regression model was used to determine the relationship between sodium to potassium ratio and risk of CVD. In addition, participants were divided into 2 subgroups by the median of overnight urinary sodium and potassium, and then combined each other for 4 subgroups including low sodium-low potassium group, low sodium-high potassium group, high sodium-low potassium group, and high sodium-high potassium group, to explore the relationship between different sodium-potassium combinations and the risk of CVD. Results: A total of 954 participants were included in the final analysis, of whom 459 (48.1%) were males. There were 318 cases in the first, second and third ratio group, respectively. There were 347 cases in low sodium-low potassium group and high sodium-high potassium group, and 130 cases in low sodium-high potassium group and high sodium-low potassium group. After a median follow-up of 18.6 (18.3, 19.3) years, cardiovascular events occurred in 81 participants, including 64 stroke and 20 coronary heart disease events. Multivariate analysis showed that comparing with the first ratio group, the hazard ratios (HR) in the second and the third ratio groups were 2.04 (95%CI 1.06-3.95, P=0.034) and 2.07 (95%CI 1.07-4.03, P=0.032), respectively. The CVD risk in low sodium-low potassium group was 24% higher than the low sodium-high potassium group (reference), but this result did not reach statistical significant level (P=0.685). The risks in high sodium-high potassium group (HR=3.32, 95%CI 1.26-8.76,P=0.015) and high sodium-low potassium (HR=3.04, 95%CI 1.05-8.83, P=0.041) group were both significantly increased. Conclusions Overnight urinary sodium to potassium ratio is positively correlated with the risk of cardiovascular events. High urinary sodium plays a more important role for the increased risk of cardiovascular events than low potassium.

[Objective]To evaluate the effects of sutureless technique in comparison to conventional techniques for repair of total anomalous pulmonary venous connection(TAPVC)with the method of propensity score analysis.[Methods]From October 2007 to December 2013,179 consecutive patients were enrolled in this study. Patients were operated with sutureless technique(n = 81)or Conventional technique(n=98),and followed up at an interval of 1 month,3 months,6 months and then once a year post-operation. During analysis,three type of propensity-score matching methods,including nearest neighbor caliper matching,Mahalanobis metric matching with propensity score ,optimal full matching were used to create balanced groups of patients receiving each treatment. Surgeons’performance difference was assessed with random frailty proportional hazards models with gamma. Composite endpoints was defined by postoperative death or late death or postoperative pulmonary venous obstruction(PVO),which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model,adjusted by Preoperative-PVO,age,gender,weight and TAPVC type.[Results]Nearest neighbor caliper matching method was the best choice during propensity score analysis. After matching ,sutureless group included 73 patients and Conventional group73 patients. In sutureless group,cardiopulmonary bypass(CPB)time(Z=2.18, P=0.030),cross-clamp time(Z=3.63,P<0.001),rate of composite endpoints(HR 95%CI=0.20(0.06~0.61),P=0.005),late death(HR 95%CI=0.03(0.01~0.55),P=0.017)were significantly better than that in Conventional group. In subgroup analysis ,for patients with pre-PVO,decreased composite endpoints was seen in sutureless group.[Conclusion]Comparison using thepropensity score analysis demonstrated that sutureless strategy for primary repair of TAPVC may associate with decreased mortality rate of post-PVO and CPB time and cross-clamp time.

Objective This retrospective cohort study aims to evaluate and compare the prognosis of surgical repair for total anomalous pulmonary venous connection(TAPVC) with different drainage type.Methods From January 2006 to Decem-ber 2013, 328 consecutive patients were enrolled in this study .The distribution of the defects was 109 cases with cardiac, 161 with supracardiac, 32 with infracardiac, and 26 with mixed type of the drainage into the systemic circulation .The clinical re-cords of all the patients were reviewed.Studied variables were extracted from the clinical records.Followed-up was conducted at an interval of 1 month, 3 months, 6 months and then once a year post-operation.Prevalence of peri-operative conditions were compared among four different types.Studied endpoints was defined by postoperative total death or pulmonary venous obstruc-tion(PVO), which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model, adjusted by differ-ent surgical strategy, emergency operation, preoperative-PVO, neonates, weight, combing with other complex cardiac defects,NYHA cardiac function, severe pulmonary hypertension and severe tricuspid regurgitation.Results There were significant discrepancyof preoperative conditions among four types of TAPVC.Patients with infracardiac TAPVC presented the most criticalsymptoms and clinical indexes, which included having largest proportion of neonates, preoperative PVO, severe NYHA grading,pulmonary hypertension and tricuspid regurgitation, having lowest body weight at operation and youngest age.The cardiopulmonarybypass time, aortic crossclamp time and mechanical ventilation time were significantly longer in infracadiac and mixedTAPVC comparing to the other two types.For early mortality(death in hospital), infracadiac(9.4%) and mixed(11.5%)TAPVC demonstrated higher rates of death than cardiac(4.6%) and supracardiac(7.5%)TAPVC, although had no statisticalsignificance.For intermediate-term results, mortality in infracadiac(21.9%) and mixed(30.8%) TAPVC were significantlyhigher than cardiac ( 8.3%) and supracardiac (11.8%) TAPVC.Reoperation was more frequently required in mixed(19.2%), then infracadiac(15.6%)TAPVC.Mixed and infracadiac types are independent risk factors for TAPVC prognosis,after adjusting by the confounding factors.Conclusion Mixed and infracadiac types are independent risk factors for postoperativedeath and PVO among TAPVC patients.This study provided evidence for clinical assessment and management strategy fordifferent types of TAPVC.