OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To investigate the current status of quality management in clinical pharmacist training bases in China， and to provide references for the standardized development and improvement of these bases. METHODS A combined approach of questionnaire survey and on-site investigation was adopted， targeting the healthcare highly sought-after talent （clinical pharmacist） training bases in 31 provinces of China as well as the clinical pharmacist training bases affiliated with the Chinese Hospital Association. A training quality management evaluation index system consisting of 25 tertiary indicators was established. Investigations were conducted from two dimensions： structural quality of training and quality management of training processes. Data were statistically analyzed using descriptive statistical methods. RESULTS On-site investigations were completed for 297 clinical pharmacist training bases across the 31 provinces， among which 284 were affiliated with the Chinese Hospital Association and 271 were healthcare highly sought-after talent （clinical pharmacist） training bases. In terms of structural quality， the core indicator compliance rate for hospital-level training systems exceeded 80%， the rate of special fund utilization for designated purposes reached 80.13%， and the overall compliance rate for software and hardware facilities surpassed 88%. A total of 1 348 preceptors were employed across the training bases， among whom those with senior professional titles and full-time specialist clinical pharmacists as lead preceptors accounted for 62.91% and 94.36%， respectively. Regarding process quality， the compliance rate for “establishment of clinical practice teaching groups in accordance with regulations during clinical department rotations” was 85.19%， and 79.80% and 76.09% of the bases were found to implement strict confidentiality in theoretical examinations and meet the required scale of assessment cases， respectively. However， formal documents of corresponding training management regulations were formulated in only 57.91% of the bases， and the completeness and standardization rate of training manual completion was merely 47.47%. In addition， considerable disparities in quality management levels were observed among provinces， with issues in training process quality being particularly prominent. CONCLUSIONS The management system， hardware facilities， and preceptor staffing of clinical pharmacist training bases in China are relatively well-established， yet notable variations in quality management exist among training bases across different provinces.

Objective: To investigate the efficacy and safety of centrifugal and membrane double plasma molecular adsorption systems (DPMAS) combined with low-dose plasma exchange in the treatment of liver failure. Methods: A retrospective analysis was performed on 60 patients with liver failure treated in our hospital from April 2024 to June 2025. Based on different plasma separation methods, they were divided into the centrifugal DPMAS group (n=30) and the conventional membrane DPMAS group (n=30). The operational parameters, laboratory indicators, and adverse reactions were compared between the two groups. Results: Under the same plasma volume for adsorption and exchange (P>0.05), the centrifugal group showed lower total circulating blood volume, total blood flow rate, and treatment duration compared to the membrane group [10 794 (9 532, 12 637) vs 19 000 (19 000, 21 000) mL, 60 (60, 65) vs 125 (120, 130) mL/min, 169 (141, 193) vs 207 (183, 210) min, P<0.001]. The centrifugal group also had a lower rate of central venous catheter use [(24/30, 80.00%) vs (30/30, 100.00%), P=0.024] and required more calcium supplementation due to sodium citrate anticoagulation [6 (6, 8) vs 2 (2, 2) g, P<0.001]. No significant changes were observed in WBC, Hb, HCT, and PLT levels before and after treatment with the centrifugal group (P>0.05). There was no statistically significant difference in WBC levels before and after membrane group treatment (P=0.199), but the values of Hb, HCT, and PLT showed significant decreases post-treatment compared to pre-treatment [106.50 (102.75, 126.75) vs 123.00 (109.75, 132.00) g/L, 33.20 (29.90, 34.92) vs 34.85 (31.55, 37.52)%, 85.00 (43.25, 139.50) vs 93.00 (61.50, 145.00)×10 /L, P<0.05]. There was no significant difference in coagulation function indexes before and after treatment with centrifugal group (P>0.05). The membrane group showed reduction in fibrinogen (Fib) levels post-treatment [1.50 (1.20, 1.60) vs 1.60 (1.25, 1.80) g/L, P=0.033]. Both groups demonstrated significant decreases in total bilirubin (TBil) and direct bilirubin (DBil) levels after treatment (centrifugal group: 194.70 (107.50, 276.00) vs 239.15 (173.00, 304.17) μmol/L, 101.00 (64.00, 182.30) vs 157.00 (101.00, 195.00) μmol/L; membrane group: 211.50 (118.00, 240.00) vs 263.50 (204.75, 314.00) μmol/L, 188.00 (122.75, 232.25) vs 219.00 (178.50, 267.25) μmol/L, P<0.05]. The incidence of catheter-related complications was lower in the centrifugal group [(2/30, 6.67%) vs (8/30, 26.67%), P=0.038]. Conclusion: The centrifugal DPMAS system demonstrates advantages such as lower blood flow velocity requirements, shorter treatment duration, minimal impact on platelets, and reduced adverse event rates, indicating promising clinical applications.

[摘 要] 目的：探讨X连锁锌指蛋白（ZFX）通过Nectin-4表达影响食管鳞状细胞癌（ESCC）进展的分子机制及其对PI3K/AKT信号通路的激活作用。方法：收集2022年8月至2023年7月在南充市中心医院手术切除的30对ESCC组织及癌旁组织标本。采用人食管上皮细胞HET-1A及ESCC细胞KYSE-30、KYSE-150、KYSE-410、KYSE-510和TE-1。基于2018年至2019年收集的6例ESCC配对标本转录组测序数据筛选Nectin-4，通过TIMER2.0数据库、RT-qPCR和WB法、免疫组织化学（IHC）检测ESCC组织及细胞中Nectin-4的表达水平。采用shRNA技术在KYSE-410和KYSE-510细胞中敲低Nectin-4，通过CCK-8、克隆形成、划痕愈合及Transwell实验检测敲低Nectin-4对细胞增殖、迁移和侵袭能力的影响，采用WB法检测敲低Nectin-4对细胞PI3K/AKT通路及EMT相关蛋白表达水平的影响。通过生物信息学预测并结合双萤光素酶报告基因实验，鉴定并验证ZFX作为Nectin-4的上游转录调控因子。结果：综合分析显示，ESCC组织及细胞系中Nectin-4表达显著高于癌旁组织及HET-1A细胞（均P < 0.01）。功能研究表明，敲低Nectin-4显著抑制KYSE-410和KYSE-510细胞的增殖活性、克隆形成能力，以及迁移和侵袭能力（均P < 0.01）。机制方面，敲低Nectin-4时细胞中E-cadherin表达上调、N-cadherin下调（均P < 0.01），并抑制PI3K/AKT通路相关蛋白的磷酸化水平（P < 0.01）。结论： ZFX通过上调Nectin-4表达激活PI3K/AKT信号通路促进ESCC进展，为ESCC的治疗提供了潜在的新靶点。

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

Objective:To understand the factors influencing new infections of 9-valent vaccine-type human papillomavirus (9-valent type HPV) among men who have sex with men (MSM) in Urumqi City and to construct a prediction model of individual dynamics of new infections of 9-valent type HPV among MSM.Methods:In this study, a snowball method was adopted to recruit MSM in Urumqi City to establish a dynamic cohort, and participants were followed up every 6 months from 2016 to 2023, and perianal exfoliated cells were collected for HPV genotyping; joint models were established using the number of same-sex sexual partners in the last six months and the number of anal intercourse in the last one week as longitudinal variables, respectively, and joint models were utilized to analyze the influence factors of 9-valent HPV new infections in MSM individuals were analyzed by the joint model; the predictive efficacy of the model in the follow-up period was evaluated by using the time-dependent receiver operating characteristic area under the curve (AUC) values. Based on the prediction model, two study participants were randomly selected for individual dynamic prediction of new-onset HPV infections of 9-valent type types.Results:MSM with at least two follow-up visits 579 individuals were included in the analysis. The results of the two joint models showed that being divorced/widowed [hazard ratio ( HR)=1.544, 95% CI: 1.033-2.233], having a sexual behavior style of being the inserted party ( HR=1.366, 95% CI: 1.053-1.764), and having a history of STDs ( HR=1.659, 95% CI: 1.057-2.558) increased the 9-valent types of new HPV infections risk. The results of the shared parameter of the joint model of the number of same-sex partners in the last six months showed that each 2.72 increase in the number of same-sex partners in the last six months was associated with a 28.2% increase in the risk of new 9-valent HPV infections in MSM individuals ( HR=1.282, 95% CI: 1.065-1.540). The time-dependent AUC results showed that the joint model for the number of same-sex sexual partners in the last six months (0.808 0) predicted better performance than the joint model for the number of anal intercourse in the last one week (0.750 0). The joint model based on the number of same-sex sexual partners in the last six months for the prediction of MSM individual dynamics was consistent with the real situation. Conclusion:The joint model based on the number of same-sex sexual partners in the last six months, sexual behavior, history of STDs, and other risk factors has high accuracy in predicting the risk of new MSM 9-valent HPV infections in Urumqi City, which can provide a scientific basis for the prediction of individual dynamics of new MSM 9-valent HPV infections.

Objective:To analyze the efficacy of phantom-less quantitative computer tomography (PL-QCT) for the diagnosis of osteoporosis in patients with lumbar degenerative diseases.Methods:From October 2021 to October 2023, a total of 1 248 patients with lumbar degenerative disease who did not receive anti-osteoporosis treatment in the Department of Spine Surgery, Tianjin Hospital were retrospectively analyzed. There were 520 males and 728 females, aged 62.31±9.37 years (range, 40-87 years), height 1.66±0.08 m (range, 1.43-1.89 m), weight 69.04±8.27 kg (range, 49-93 kg). The mean body mass index was 26.11±3.67 kg/m 2 (range, 14.40-37.11 kg/m 2). Dual-energy X-ray absorptiometry (DXA) and PL-QCT were used to diagnose osteoporosis, and the detection rates of the two diagnostic methods were compared. The receiver operating characteristic (ROC) curve of PL-QCT for the diagnosis of osteoporosis was drawn, the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity were calculated. Results:Among 1 248 patients with lumbar degenerative diseases, 626 (50.2%) were diagnosed as osteoporosis by PL-QCT, 423(33.9%) were diagnosed by spine DXA, 488(39.1%) were diagnosed by hip DXA and 539 patients(43.2%) were diagnosed by dual-site DXA. The detection rate of osteoporosis of PL-QCT was higher than that of spine DXA (χ 2=193.557, P<0.001), hip DXA (χ 2=322.201, P<0.001) and dual-site DXA (χ 2=94.683, P<0.001), and the difference was statistically significant. Taking the diagnostic results of spinal DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 79%, a specificity of 81%, and an AUC and 95% CI of 0.82(0.79, 0.85). Taking the diagnostic results of hip DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 85%, a specificity of 55%, and an AUC and 95% CI of 0.75(0.71, 0.78). Taking the diagnostic results of two-site DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 72%, a specificity of 75%, and an AUC and 95% CI of 0.81(0.78, 0.83). Conclusion:Compared with DXA, PL-QCT has a higher detection rate of osteoporosis in patients with degenerative lumbar spine disease and good diagnostic efficacy.