OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of apixaban in the prevention and treatment of cancer-associated venous thromboembolism （CA-VTE）， and provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， CNKI， Wanfang， VIP database and other websites of health technology assessment （HTA）， systematic review/meta-analysis， pharmacoeconomic studies and HTA reports of apixaban in the prevention and treatment of CA-VTE were collected. After data extraction and quality evaluation， the results of the included study were analyzed descriptively. RESULTS A total of 23 literatures were included， involving 16 systematic review/meta-analysis and 7 pharmacoeconomic studies. In terms of efficacy， compared with placebo， prophylactic use of apixaban could significantly reduce the incidence of venous thromboembolism （VTE） in outpatient adult cancer patients receiving chemotherapy （P＜0.05）. Compared with low-molecular weight heparin （LMWH）， rivaroxaban and warfarin， there were no statistically significant differences in the incidence of VTE for apixaban （P＞0.05）； nevertheless， apixaban was ranked as the most preferable choice. For the treatment of patients with CA-VTE， compared with warfarin， apixaban could significantly reduce the recurrence rate of VTE （P＜0.05）. While compared with patients treated with LMWH， rivaroxaban， edoxaban and dabigatran， there were no statistically significant differences in the recurrence rates of VTE， deep venous thrombosis and pulmonary embolism among patients using apixaban （P＞0.05）. In terms of safety， compared with placebo， prophylactic use of apixaban showed a higher occurrence of major bleeding in outpatient adult cancer patients receiving chemotherapy （P＜0.05）， while compared withpatients treated with LMWH， rivaroxaban， and warfarin， there were no statistically significant differences in the incidence of major bleeding among patients using apixaban （P＞0.05）； despite this， apixaban was ranked as the most favorable option. For the treatment of patients with CA-VTE， compared with dalteparin， the incidence of major bleeding and all-cause mortality of apixaban were similar （P＞0.05）， while the incidence of clinically relevant non-major bleeding （CRNMB） was higher （P＜0.05）. Compared with edoxaban， the incidence of major bleeding of apixaban was reduced significantly （P＜0.05）， while there was no significant difference in the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. Compared with rivaroxaban， warfarin and dabigatran， there were no significant differences in the incidence of major bleeding， the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. In terms of cost-effectiveness， the researches in China showed that apixaban was cost-effective in preventing CA-VTE； foreign studies showed that apixaban was cost-effective in preventing and treating CA-VTE. CONCLUSIONS Apixaban is effective， safe and cost- effective in the prevention and treatment of CA-VTE.

[摘 要] 尽管基于T细胞的免疫检查点阻断（ICB）和过继性T细胞治疗已在临床上取得了显著疗效，但大多数实体瘤患者仍无法实现对免疫疗法的长期应答。其中一个重要原因是肿瘤微环境（TME）中复杂的代谢模式和抑制性信号会引发免疫细胞的代谢重编程，从而削弱其抗肿瘤效应。本文回顾不同分化状态的CD8+ T细胞的代谢偏好性，探讨CD8+ T细胞在与肿瘤细胞和TME相互作用过程中发生的代谢变化，讨论这些代谢变化如何影响CD8+ T细胞分化、功能和干性，以及如何利用代谢分子或者代谢通路来增强CD8+ T细胞的抗肿瘤能力，从而实现嵌合抗原受体基因修饰T淋巴细胞（CAR-T细胞）疗法和ICB疗法增效。

Diagnostic criteria, as a critical component of clinical practice guidelines, play a direct role in guiding clinicians' diagnostic and treatment decisions. Although China has increasingly emphasized the development and updating of clinical guidelines in recent years, research focusing on the diagnostic criteria within these guidelines remains limited. This paper aims to explore the types of diagnostic criteria, the issues they present, and the processes involved in their formulation. Based on this analysis, suggestions are proposed to improve the recommendation and application of diagnostic criteria in Chinese guidelines.

Diagnostic criteria, as a critical component of clinical practice guidelines, play a direct role in guiding clinicians' diagnostic and treatment decisions. Although China has increasingly emphasized the development and updating of clinical guidelines in recent years, research focusing on the diagnostic criteria within these guidelines remains limited. This paper aims to explore the types of diagnostic criteria, the issues they present, and the processes involved in their formulation. Based on this analysis, suggestions are proposed to improve the recommendation and application of diagnostic criteria in Chinese guidelines.

  Objective  To analyze the current status of the development of adaptation guidelines in China, as well as their methodological quality and the reporting quality, in order to provide reference for the development of adaptation guidelines.  Methods  We searched and collected adaptation guidelines led by Chinese researchers or institutions from 2015 to 2023 from four electronic databases, China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, SinoMed and PubMed, extracted the basic information of the adapted guidelines, and assessed their methodological quality and reporting quality using the Appraisal of Guidelines for REsearch and Evaluation (AGREE) Ⅱ and RIGHT-Ad@pt tools.  Results  A total of 14 adaptation guidelines were included, mainly focusing on nursing (42.9%, 6/14), with the most frequently used adaptation method of ADAPTE (71.4%, 10/14), and with reference to pre-existing guidelines mainly from the United States, the United Kingdom, and international organizations. Assessment by the AGREE Ⅱ tool showed that the average methodological quality score of the adapted guidelines was 36.6%. The scores were relatively high in the domains of clarity of expression and rigor of formulation (44.4% and 54.9%), and lowest in the domain of applicability (15.3%). The results of the RIGHT-Ad@pt tool showed that the reporting quality of the adaptation guidelines was relatively good, with the highest reporting rate of 91.2% and the lowest of 35.3%, and the reporting rates of seven articles were higher than 70%.  Conclusions  Adaptation guidelines in China are still in their infancy, with a relatively small number and mainly focusing on the nursing field. The most commonly used adaptation method is the ADAPTE method. The methodological quality and reporting quality of adaptation guidelines need to be further improved, and more research should be conducted on the specific conditions and timing of adaptation guidelines development.

Objective:To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique; To explore the possibility of its treatment for cough variant asthma.Methods:The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot.Results:Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased ( P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased ( P<0.05). Conclusion:Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.

Objective:To explore the relationship between serum uric acid trajectory and the progression of renal function in individuals aged 60 and above.Methods:This study was a retrospective cohort study. Individuals aged 60 years and above who received health checkups in Beijing Friendship Hospital, Capital Medical University, from March 2015 to December 2023 and met the criteria of baseline estimated glomerular filtration rate (eGFR)≥60 ml·min -1·(1.73 m 2) -1, were selected as the research subjects. The serum uric acid data of multiple measurements were collected and identified as different serum uric acid trajectories by group-based trajectory modeling (GBTM). According to the serum uric acid trajectories, the subjects were divided into a low trajectory group (101 cases), a middle trajectory group (176 cases), and a high trajectory group (86 cases). Cox regression analysis was used to examine the effect of serum uric acid trajectory on the progression of renal function in the elderly. Results:A total of 363 elderly were included. The mean follow-up time was 8.1 years. At the end of the follow-up, a total of 50 elderly individuals had experienced varying degrees of renal function decline. After adjusting for multiple confounding factors by Cox regression analysis, the risks of eGFR<60 ml·min -1·(1.73 m 2) -1, eGFR reduction rate ≥25% and composite endpoints [eGFR <60 ml·min -1·(1.73 m 2) -1, eGFR reduction rate ≥25% or >3 ml·min -1·(1.73 m 2) -1·year -1] in the high trajectory group were significantly higher than those in the low trajectory group, with an HR of 4.54 (95% CI:1.47-20.76), 3.75 (95% CI:1.06-21.21), and 3.74 (95% CI:1.44-115.59), respectively. In addition, there was no significant difference between baseline serum uric acid and renal function progression (all P>0.05). Conclusion:The high serum uric acid trajectory increases the risk for the progression of renal function in individuals aged 60 and above.

Objective:To evaluate alteration of autograft function by pathological types after total parathyroidectomy (tPTX) plus autotransplantation (AT) in patients of hyperthyroidism.Methods:A total of 51 patients with end-stage chronic renal failure who underwent total parathyroidectomy with autologous forearm transplantation from Mar 2017 to Feb 2021 were divided into chief cell type (CC) and oxyphil cell type (OC) according to dominating graft cell type. iPTH, calcium, phosphorus and ALP levels were compared between the two groups from the perioperative period to 6 months and the 3D ultrasonography was performed at 6 months to cocalculate the size of the autograft.Results:Between the two groups, there were no statistically significant differences in iPTH, blood calcium, blood phosphorus, or ALP levels pre-,and 30 minutes, one month post surgery (all P>0.05). On three months, there was no significant difference in ALP levels [CC group: (99±23) U/L, OC group: (89±35) U/L, t=0.776, P=0.442]. At 6 months the PTH level [CC group: (290±77) pg/ml, OC group: (246±59) pg/ml, t=2.034, P=0.047], and blood calcium [CC group: (2.62±0.65) mmol/L, OC group: (2.21±0.20) mmol/L, t=2.531, P=0.015] blood phosphorus [CC group: (1.38±0.28) mmol/L, OC group: (1.68±0.34) mmol/L; t=-3.269, P=0.002], were all in favor of CC group. By 3D ultrasnography at 6 months the size of autograft was larger in CC group than in OC group [V cc=(2.17±0.37) cm 3,V oc=(1.85±0.29) cm 3, t=3.172, P<0.05]. Recurrences at 1 year after surgery were not significantly different between the two groups ( ncc=3, noc=1, t=0.277, P>0.05). Conclusion:The biological activity of CC-type grafts is higher than that of OC suggesting a longer functioning period as a parathyroid autograft.

Objective:To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants.Methods:This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1 st, 2015 to December 31 st, 2021 of the Seventh Medical Center of the People′s Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children′s Hospital from January 1 st, 2020 to December 31 st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks′ corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model′s discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results:A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95% CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions:A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

Objective To explore the effect of 4-week repetitive downhill treadmill running on the mi-tochondrial structure,function,and autophagy in skeletal muscle of rats,so as to analyze the role of FKBP8-mediated mitophagy in exercise-induced mitochondrial damage in their skeletal muscles.Meth-ods Thirty-two male adult Sprague-Dawley rats were randomly divided into a 2-week quiet control group(2C group,n=8),a 4-week quiet control group(4C group,n=8),a 2-week exercise group(2E group,n=8)and a 4-week exercise group(4E group,n=8).Rats in 2E and 4E groups performed dai-ly 90-minute downhill treadmill running(-16°,16 m/min)5 days a week for two and four weeks,re-spectively.Then,they rested for 24 hours and received an exhaustive exercise test.Running distance and blood lactate were measured prior to and at the time of exercise cessation.Moreover,mitochondri-al ultrastructural changes in soleus muscles were observed by using a transmission electron microscope.The protein expression of mitochondrial succinate dehydrogenase subunit B(SDHB),cytochrome C oxi-dase subunit 1(MTCO1),FK506 binding protein 8(FKBP8)and microtubule associated protein 1 light chain 3(LC3)in the soleus muscle were measured using Western blotting.Meanwhile,the co-localiza-tion of FKBP8 with LC3 and cytochrome C oxidase subunit Ⅳ(COXⅣ)with LC3,lysosomal associat-ed membrane protein 2(LAMP2)were detected by the immunofluorescence double labeling technique.Results(1)The running distance of one exhaustive exercise and the blood lactate before and after the test in 2E group were significantly higher than 2C and 4E groups(P<0.05 or P<0.01),and the run-ning distance of 4E group was significantly higher than 4C group(P<0.01).However,there was no sig-nificant difference between 4E and 4C groups in the blood lactate before and after the exhaustive exer-cise test(P>0.05).(2)In both 2E and 4E groups,significant mitochondrial swelling and accumulation under cell membrane,as well as a number of mitophagosomes and mitophagolysosomes were observed,together with a significant reduce in the number of mitochondria(P<0.05),which was more severe in 2E group than 4E group.(3)The protein expression of mitochondrial SDHB and MTCO1 in 2E and 4E groups were lower than 2C and 4C groups,respectively,with significantly greater changes of these proteins in 4E group than 2E group(P<0.05 or P<0.01).(4)The protein expression of mitochondrial FKBP8 and LC3,as well as the co-localization of FKBP8 with LC3 and COXⅣ with LC3,LAMP2 in 2E and 4E groups were higher than 2C and 4C groups,respectively,with significantly greater changes in 4E group than 2E group(P<0.05 or P<0.01).Conclusion After 4-week downhill treadmill running,the structure,quantity and function of mitochondria in skeletal muscle are impaired.FKBP8-mediated mitophagy is activated,but is insufficient to degrade the damaged mitochondria,leading to muscular damage,as well as the increasing and falling down of running capacity.