OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. 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 perioperative period.

Early-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.
Humans ; Colorectal Neoplasms/etiology* ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease/genetics*

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

Objective To investigate the dynamic characteristics of intestinal pathological development at different time points in a mouse model of colitis-associated colon cancer.Methods A colitis-cancer model was established in C57BL/6 mice using azoxymethane(AOM)combined with dextran sulfate sodium(DSS).Samples were collected at 7,10,and 14 weeks post-modeling and the spleen index,colon length,mass,and colon mass per unit length were measured.Histopathological changes in the colon were observed by hematoxylin and eosin and Masson staining.Expression levels of the cancer stem cell marker CD44 and Wnt signaling pathway genes Wnt2b,Lrp5,Axin2,and Znrf3 at different pathological stages were detected by reverse transcription quantitative real time PCR.Cancer-associated fibroblasts(FAP),CD44,the proliferation marker Ki67,and goblet cell MUC2 protein were detected by multiple immunofluorescence histochemistry(mIHC)and immunofluorescence.In addition,colon organoids were isolated from model mice at ten and fourteen weeks and cultured in vitro to observe changes in organoid morphology and marker expression.Results AOM/DSS-induced mice showed reduced,distorted,and branched colon crypt structures with a few collagen fibers at 7 weeks,and varying degrees of colon intraepithelial neoplasia,with an increased proportion of high-grade intraepithelial neoplasia over time and increased collagen fiber staining at ten and fourteen weeks.mRNA levels of CD44 and Wnt2b in the colon were significantly increased(P＜0.05)and Axin2 was decreased(P＜0.01)in model mice compared with control mice at fourteen week,and levels of Wnt2b,Lrp5,and Znrf3 were increased compared with seven-week mice(P＜0.01,P＜0.05,P＜0.01),and Axin2 was decreased(P＜0.01).mIHC staining showed increased expression of FAP and CD44 in the colon in model mice at ten and fourteen weeks,with decreased MUC2 expression.Colon organoids showed cystic dilation,especially at fourteen weeks,with more prominent expression of Ki67 and CD44.Conclusions The AOM/DSS-induced mouse model exhibited chronic colonic inflammation,low-grade intraepithelial neoplasia,and high-grade intraepithelial neoplasia at seven,ten,and fourteen weeks,respectively.The pathological microenvironment was characterized by fibroblast activation and abnormal proliferation of epithelial cells.

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

Objective To investigate the dynamic characteristics of intestinal pathological development at different time points in a mouse model of colitis-associated colon cancer.Methods A colitis-cancer model was established in C57BL/6 mice using azoxymethane(AOM)combined with dextran sulfate sodium(DSS).Samples were collected at 7,10,and 14 weeks post-modeling and the spleen index,colon length,mass,and colon mass per unit length were measured.Histopathological changes in the colon were observed by hematoxylin and eosin and Masson staining.Expression levels of the cancer stem cell marker CD44 and Wnt signaling pathway genes Wnt2b,Lrp5,Axin2,and Znrf3 at different pathological stages were detected by reverse transcription quantitative real time PCR.Cancer-associated fibroblasts(FAP),CD44,the proliferation marker Ki67,and goblet cell MUC2 protein were detected by multiple immunofluorescence histochemistry(mIHC)and immunofluorescence.In addition,colon organoids were isolated from model mice at ten and fourteen weeks and cultured in vitro to observe changes in organoid morphology and marker expression.Results AOM/DSS-induced mice showed reduced,distorted,and branched colon crypt structures with a few collagen fibers at 7 weeks,and varying degrees of colon intraepithelial neoplasia,with an increased proportion of high-grade intraepithelial neoplasia over time and increased collagen fiber staining at ten and fourteen weeks.mRNA levels of CD44 and Wnt2b in the colon were significantly increased(P＜0.05)and Axin2 was decreased(P＜0.01)in model mice compared with control mice at fourteen week,and levels of Wnt2b,Lrp5,and Znrf3 were increased compared with seven-week mice(P＜0.01,P＜0.05,P＜0.01),and Axin2 was decreased(P＜0.01).mIHC staining showed increased expression of FAP and CD44 in the colon in model mice at ten and fourteen weeks,with decreased MUC2 expression.Colon organoids showed cystic dilation,especially at fourteen weeks,with more prominent expression of Ki67 and CD44.Conclusions The AOM/DSS-induced mouse model exhibited chronic colonic inflammation,low-grade intraepithelial neoplasia,and high-grade intraepithelial neoplasia at seven,ten,and fourteen weeks,respectively.The pathological microenvironment was characterized by fibroblast activation and abnormal proliferation of epithelial cells.

Objective To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. Methods One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. Results A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ² = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. Conclusion Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.

Objective:To explore the effect of clinical pharmacists′ intervention in therapeutic drug monitoring (TDM) of voriconazole on medication safety.Methods:The study subjects were inpatients with fungal infection, admitted from January 2019 to June 2020 in the Department of Infectious Diseases, West China Hospital, Sichuan University, who were scheduled to be treated with voriconazole. Using random-cluster method, patients were divided into intervention group and control group based on their doctor medical groups. In the intervention group, clinical pharmacists participated in the whole process of voriconazole TDM and provided pharmaceutical care, while in the control group, no clinical pharmacists participated in TDM. The percentage of voriconazole-treated patients achieved target trough concentration(1.5-5.5 mg/L), the incidence of adverse reactions, and clinical cure rate between the 2 groups were compared. The timely (within 24 hours) management rate of medication orders containing drugs with interaction by doctors and the detection frequency of blood drug concentration were compared between the 2 groups.Results:A total of 303 patients were enrolled in the analysis, including 166 in the intervention group and 137 in the control group. There was no significant difference between the 2 groups in demographic characteristics, liver function indexes, types of fungal diseases, main combined diseases, and the use of drugs with interactions with voriconazole before voriconazole treatment (all P>0.05). After receiving voriconazole, percentage of patients achieved target trough concentration in the intervention group was similar to that in the control group in the first detection [55% (91/166) vs. 50% (69/137), P=0.440] while significantly higher in the last detection[81% (134/166) vs. 47% (65/137), P<0.001]. The total frequency of trough concentration detection in the intervention group and the control group were 403 and 244 respectively. Percentage of detection values consisted with target trough concentration was significantly higher, while percentage of detection values exceeding target trough concentration (>5.5 mg/L) was significantly lower in the intervention group than those in the control group, respectively [63% (254/403) vs. 44% (107/244), P<0.001; 19% (63/403) vs. 22% (54/244), P=0.037)]. The total incidence of voriconazole-related adverse reactions [14% (23/166) vs. 23% (31/137)], the incidence of severe adverse reactions [2% (4/166) vs. 8% (11/137)], and incidence of liver injury [Council for International Organizations of Medical Sciences standard: 8% (13/166) vs. 15% (21/137); International Drug-induced Liver Injury Expert Working Group standard: 2% (4/166) vs. 7% (10/137)] in the intervention group were significantly lower than those in the control group (all P<0.05), and the clinical cure rate was similar in the 2 groups [86% (142/166) vs. 81% (111/137), P=0.291]. In the intervention and control groups, some patients were using drugs which had interactions with voriconazole when starting voriconazole treatment, and the timely management rates of these medication orders were 71% (24/17) and 18% (3/17) respectively, with a statistically significant difference between the 2 groups ( P=0.001). The detection frequency of voriconazole trough concentration in the intervention group (2.4 times per patient) was higher than that in the control group (1.8 times per patient), and the proportion of patients with ≥3 detection was significantly higher [38% (63/166) vs. 23% (32/137), P=0.006]. Conclusion:The involvement of clinical pharmacists in voriconazole TDM can enlarge the percentage of patients who achieve target trough concentration, improve the timely management rate of medication orders containing drugs with interactions with voriconazole, reduce the incidence of voriconazole-related adverse reactions, and improve medication safety.

Objective:To explore the effect of clinical pharmacists′ intervention in therapeutic drug monitoring (TDM) of voriconazole on medication safety.Methods:The study subjects were inpatients with fungal infection, admitted from January 2019 to June 2020 in the Department of Infectious Diseases, West China Hospital, Sichuan University, who were scheduled to be treated with voriconazole. Using random-cluster method, patients were divided into intervention group and control group based on their doctor medical groups. In the intervention group, clinical pharmacists participated in the whole process of voriconazole TDM and provided pharmaceutical care, while in the control group, no clinical pharmacists participated in TDM. The percentage of voriconazole-treated patients achieved target trough concentration(1.5-5.5 mg/L), the incidence of adverse reactions, and clinical cure rate between the 2 groups were compared. The timely (within 24 hours) management rate of medication orders containing drugs with interaction by doctors and the detection frequency of blood drug concentration were compared between the 2 groups.Results:A total of 303 patients were enrolled in the analysis, including 166 in the intervention group and 137 in the control group. There was no significant difference between the 2 groups in demographic characteristics, liver function indexes, types of fungal diseases, main combined diseases, and the use of drugs with interactions with voriconazole before voriconazole treatment (all P>0.05). After receiving voriconazole, percentage of patients achieved target trough concentration in the intervention group was similar to that in the control group in the first detection [55% (91/166) vs. 50% (69/137), P=0.440] while significantly higher in the last detection[81% (134/166) vs. 47% (65/137), P<0.001]. The total frequency of trough concentration detection in the intervention group and the control group were 403 and 244 respectively. Percentage of detection values consisted with target trough concentration was significantly higher, while percentage of detection values exceeding target trough concentration (>5.5 mg/L) was significantly lower in the intervention group than those in the control group, respectively [63% (254/403) vs. 44% (107/244), P<0.001; 19% (63/403) vs. 22% (54/244), P=0.037)]. The total incidence of voriconazole-related adverse reactions [14% (23/166) vs. 23% (31/137)], the incidence of severe adverse reactions [2% (4/166) vs. 8% (11/137)], and incidence of liver injury [Council for International Organizations of Medical Sciences standard: 8% (13/166) vs. 15% (21/137); International Drug-induced Liver Injury Expert Working Group standard: 2% (4/166) vs. 7% (10/137)] in the intervention group were significantly lower than those in the control group (all P<0.05), and the clinical cure rate was similar in the 2 groups [86% (142/166) vs. 81% (111/137), P=0.291]. In the intervention and control groups, some patients were using drugs which had interactions with voriconazole when starting voriconazole treatment, and the timely management rates of these medication orders were 71% (24/17) and 18% (3/17) respectively, with a statistically significant difference between the 2 groups ( P=0.001). The detection frequency of voriconazole trough concentration in the intervention group (2.4 times per patient) was higher than that in the control group (1.8 times per patient), and the proportion of patients with ≥3 detection was significantly higher [38% (63/166) vs. 23% (32/137), P=0.006]. Conclusion:The involvement of clinical pharmacists in voriconazole TDM can enlarge the percentage of patients who achieve target trough concentration, improve the timely management rate of medication orders containing drugs with interactions with voriconazole, reduce the incidence of voriconazole-related adverse reactions, and improve medication safety.

Objective To observe the clinical efficacy of Bu Shen Tiao Qi(supplementing the kidney and regulating qi) needling in treating perimenopausal syndrome.Method Fifty patients were randomized into two groups, 25 cases each. The treatment group was intervened by Bu Shen Tiao Qineedling combined with electroacupuncture, while the control group was by shallow needling plus sham electroacupuncture. Kupperman Index (KI) wasobserved respectively before treatment, after 2-week and 4-week treatment, and in the 4-week follow-up study. The differences of scores and improvements of the 13 symptoms listed in KI were calculated.Result The total effective rate was 92.0% in the treatment group versus 44.0% in the control group; in the treatment group, the KI scores after 2-week treatment and in the 4-week follow-up study were significantly different from that before treatment (P<0.05), and a more significant difference was found after 4-week treatment (P<0.01); the between-group differences were statistically significant in comparing KI (P<0.05).Conclusion Bu Shen Tiao Qineedling can produce a satisfactory efficacy in treating perimenopausal syndrome.