Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Sepsis-acquired weakness (SAW) is a common complication in critically ill patients, yet significant gaps remain in both mechanistic understanding and therapeutic interventions for this condition. SAW not only prolongs the duration of mechanical ventilation and hospitalization but is also closely associated with increased mortality. Even if these SAW patients survive, they often experience long-term physical dysfunction after hospital discharge, leading to diminished quality of life. Emerging evidence suggests that sustained mitochondrial dysfunction may constitute a pivotal pathophysiological basis for the development and progression of SAW, primarily encompassing five key aspects: dysregulated mitochondrial quality control (MtQC), impaired oxidative phosphorylation (OXPHOS), exacerbated oxidative stress, disrupted Ca²⁺; homeostasis, and their mediation of diverse myofiber injuries. This article systematically elucidates the central role of mitochondrial dysfunction in the pathogenesis of SAW. Furthermore, we explore potential therapeutic strategies targeting mitochondrial function, including mitigating mitochondrial oxidative stress, optimizing nutritional support, and supplementing with muscle-derived mesenchymal stem cells. These insights provide a critical theoretical framework for understanding SAW mechanisms and developing clinical interventions, with particular emphasis on the translational value of mitochondrial-targeted therapies in improving outcomes for septic patients.
Humans ; Sepsis/metabolism* ; Mitochondria/metabolism* ; Muscle Weakness/etiology* ; Oxidative Stress ; Oxidative Phosphorylation

Objective:To investigate the effectiveness of the 5A (Ask, Assess, Advise, Assist, Arrange follow-up) management model based on personalized health education records in community patients with type 2 diabetes mellitus.Methods:A convenience sampling method was used to select patients with type 2 diabetes mellitus who were enrolled with family doctors in Yuxin Community, Haidian District, Beijing, from January 2022 to May 2023. Using a random number table method, the patients were divided into an observation group ( n=68) and a control group ( n=68). The control group received routine community management, while the observation group received management based on the 5A model and personalized health education records. Differences in metabolic indicators, including glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, body mass index (BMI), and waist circumference, as well as self-management behaviors were compared between the two groups at 3, 6, and 12 months of intervention. Results:During the entire intervention period, four cases were lost in the observation group and eight cases were lost in the control group. Finally, data from 124 patients were included in the analysis, including 64 cases in the observation group and 60 cases in the control group. Repeated measures analysis of variance showed interaction effects between time points and groups for HbA1c, BMI, waist circumference, and self-management behavior scores among patients with diabetes, with statistically significant differences ( P<0.05) . Conclusions:The 5A management model based on personalized health education records has a positive impact on improving metabolic indicators and self-management behaviors in community patients with type 2 diabetes mellitus.

Objective:To investigate the effectiveness of the 5A (Ask, Assess, Advise, Assist, Arrange follow-up) management model based on personalized health education records in community patients with type 2 diabetes mellitus.Methods:A convenience sampling method was used to select patients with type 2 diabetes mellitus who were enrolled with family doctors in Yuxin Community, Haidian District, Beijing, from January 2022 to May 2023. Using a random number table method, the patients were divided into an observation group ( n=68) and a control group ( n=68). The control group received routine community management, while the observation group received management based on the 5A model and personalized health education records. Differences in metabolic indicators, including glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, body mass index (BMI), and waist circumference, as well as self-management behaviors were compared between the two groups at 3, 6, and 12 months of intervention. Results:During the entire intervention period, four cases were lost in the observation group and eight cases were lost in the control group. Finally, data from 124 patients were included in the analysis, including 64 cases in the observation group and 60 cases in the control group. Repeated measures analysis of variance showed interaction effects between time points and groups for HbA1c, BMI, waist circumference, and self-management behavior scores among patients with diabetes, with statistically significant differences ( P<0.05) . Conclusions:The 5A management model based on personalized health education records has a positive impact on improving metabolic indicators and self-management behaviors in community patients with type 2 diabetes mellitus.

Objective To evaluate the effect of different honey processing methods on the dissolution of Cynanchum salicifolia in vitro.Methods High performance liquid chromatography ① Carotene and β-Determination method of sitosterol content:chromatographic column:Dia monosil C18(250 mm×4.6 mm,5 μm).Mobile phase:methanol:0.05％phosphoric acid water=99∶1.Isocratic elution;Flow rate 1.0 mL·min-1;Detection wavelength 209 nm;Injection volume 10 μL.The column temperature is 30℃.②Determination method of glucose and fructose:the chromatographic column is Inspire NH2 sugar analysiscolumn(250 mm×4.6 mm,5 μm).The mobile phase was acetonitrile water(77∶23).The flow rate is 0.8 mL·min-1;The column temperature is 35℃;Injection volume 10 μL;Evaporative light scattering detector(ELSD):the drift tube temperature is 100℃,and the carrier gas flow rate is 2.8 L·min-1.Results ①The results showed that carotene and β-the determination of sitosterol showed a good linear relationship in the range of mass concentration(r＞0.9999).The average recoveries were 99.71％and 98.83％.The RSD of precision,stability and repeatability were all less than 2.0％.②The established method of glucose fructose showed a good linear relationship in the range of 0.05-0.50 mg·mL-1(r=0.9991).Conclusion The content determination method and in vitro dissolution test methodology of the study meet the requirements,which provides a scientific basis for the establishment of quality standards and modern research of honey roasted Paeonia salicifolia.

Objective To evaluate the effect of different honey processing methods on the dissolution of Cynanchum salicifolia in vitro.Methods High performance liquid chromatography ① Carotene and β-Determination method of sitosterol content:chromatographic column:Dia monosil C18(250 mm×4.6 mm,5 μm).Mobile phase:methanol:0.05％phosphoric acid water=99∶1.Isocratic elution;Flow rate 1.0 mL·min-1;Detection wavelength 209 nm;Injection volume 10 μL.The column temperature is 30℃.②Determination method of glucose and fructose:the chromatographic column is Inspire NH2 sugar analysiscolumn(250 mm×4.6 mm,5 μm).The mobile phase was acetonitrile water(77∶23).The flow rate is 0.8 mL·min-1;The column temperature is 35℃;Injection volume 10 μL;Evaporative light scattering detector(ELSD):the drift tube temperature is 100℃,and the carrier gas flow rate is 2.8 L·min-1.Results ①The results showed that carotene and β-the determination of sitosterol showed a good linear relationship in the range of mass concentration(r＞0.9999).The average recoveries were 99.71％and 98.83％.The RSD of precision,stability and repeatability were all less than 2.0％.②The established method of glucose fructose showed a good linear relationship in the range of 0.05-0.50 mg·mL-1(r=0.9991).Conclusion The content determination method and in vitro dissolution test methodology of the study meet the requirements,which provides a scientific basis for the establishment of quality standards and modern research of honey roasted Paeonia salicifolia.

The present study aims to explore the genetic diversity of germplasm resources of Chrysanthemum×morifolium (hereinafter, C.×morifolium) at the molecular level and to establish a fingerprint database of C.×morifolium varieties. We employed 12 pairs of primers with high levels of polymorphism, clear bands, and high degrees of reproducibility to analyze the SSR molecular markers and genetic diversity of 91 C.×morifolium materials and 14 chrysanthemum- related materials. With regard to constructing the fingerprints of the tested materials, we chose 9 pairs of core primers. The findings revealed that 12 primer pairs detected 104 alleles in 105 samples, ranging from 2 to 26. The average number of observed alleles (N_a) per site was 9.25. The average number of effective alleles (N_e) per site was 2.745 6, with its range being 1.276 0 to 4.742 5. Shannon genetic diversity index (I) values ranged between 0.513 3 and 2.239 9 (M=1.209 0). Nei's gene diversity index (H) ranged between 0.216 3 and 0.789 1 (M=0.578 0). The observed heterozygosity (H_o) ranged between 0.223 3 and 0.895 2 (M=0.557 5). The expected heterozygosity (H_e) ranged between 0.217 4 and 0.793 3 (M=0.580 8). The polymorphism information content (PIC) ranged between 0.211 5 and 0.774 0 (M=0.532 9). The genetic similarity (GS) ranged between 0.228 5 and 1.000 0 (M=0.608 3). Cluster analysis revealed that when the genetic distance (GD) equals to 0.30, the tested materials can be classified into 2 groups. When the GD equals to 0.27, the first group can be divided into 6 subgroups; accordingly, 105 tested materials can be divided into 7 subgroups. The cophenetic correlation test was carried out based on the cluster analysis, and the corresponding results showed that the cluster map correlated with the genetic similarity coefficient (r=0.952 73). According to the results of Structure population analysis, we obtained the optimal population number, with the true number of populations (K) being 3 and the population being divided concerning Q≥0.5. Three subgroups, i.e., Q1, Q2 and Q3, included 34, 33 and 28 germplasms, respectively, and the remaining 10 germplasms were identified as the mixed population. During the experiment, 9 pairs of core primers were screened among the total of 12 for a complete differentiation regarding 105 tested materials, and the fingerprints of 91 C.×morifolium materials and 14 chrysanthemum-related materials were further constructed. Overall, there were significant genetic differences and rich genetic diversity among C.×morifolium materials, which would shed light on the garden application and variety selection fields of C.×morifolium. The fingerprint database of 105 C.×morifolium varieties and chrysanthemum-related species may provide technical support for future research regarding the identification and screening system of C.×morifolium varieties.
Genetic Variation ; Chrysanthemum/genetics* ; Reproducibility of Results ; Microsatellite Repeats/genetics* ; Polymorphism, Genetic ; Biomarkers ; Phylogeny

Objective:To explore the intervention effect of Shumu Peitu herb-partitioned moxibustion on clinical signs and symptoms and negative emotions of diarrhea-predominant irritable bowel syndrome (IBS-D) patients with liver-stagnation and spleen-deficiency pattern.Methods:A total of 72 patients with IBS-D of liver-stagnation and spleen-deficiency pattern treated in the Department of Gastroenterology of Nanjing Vniversity of Chinese Medicine from September 2021 to June 2022 were selected for randomized controlled trial. The patients were randomly divided into the observation group (2 cases dropped off, 34 cases in total) and control group (1 case dropped off, 35 cases in total) by random number table method. The patients in control group were treated with Tongxieyaofang (TXYF). The patients in observation group were treated with oral administration of TXYF and Shumu Peitu herb-partitioned moxibustion, and both groups were treated for 4 weeks. The clinical efficacy, Traditional Chinese Medicine (TCM) syndrome integral, IBS Quality of Life Questionnaire (IBS-QOL), IBS Symptom Severity Scale (IBS-SSS), Bristol Stool Form Scale and Hospital Anxiety and Depression Scale (HADS) were compared before and after treatment.Results:After treatment, the total effective rate of the observation group was 94.12%(32/34), which was higher than the 71.43%(25/35) in the control group, the difference was significant ( χ2 = 6.18, P<0.05). After treatment, the TCM syndrome integral in the observation group was (7.62 ± 4.08), which was lower than the (9.89 ± 4.71) in the control group, the difference was significant ( t = 2.14, P<0.05). After treatment of 3 days, the scores of quality of life in the five dimensions of dysthymia, behavior disorder, health worry, avoidance of eating and social function in the observation group were (82.44 ± 11.46), (80.25 ± 11.67), (76.23 ± 12.67), (59.80 ± 15.14) and (79.23 ± 11.59) points, which were different with the (73.57 ± 12.39), (72.35 ± 15.48), (69.76 ± 13.11), (50.00 ± 16.17) and (73.04 ± 13.11) points in the control group, the difference were significant ( t values were -3.09 - -2.08, all P<0.05). Three days after treatment, the score of IBS-SSS and Bristol fecal character in the observation group were (118.24 ± 40.64) and (5.09 ± 0.62) points, which were lower than the (146.86 ± 60.09) and (5.51 ± 0.66) points in the control group, the difference were significant ( t = 2.31 and 2.76, both P<0.05). After treatment, the score of HADS-A and HADS-D in the observation group were (6.26 ± 1.75) and (5.29 ± 1.47), which were different with the (7.26 ± 2.19) and (6.17 ± 2.11) in the control group, the difference were significant ( t = 2.08 and 2.00, both P<0.05). Conclusions:Shumu Peitu herb-partitioned moxibustion can effectively improve IBS-D patients with liver-stagnation and spleen-deficiency pattern, relieve clinical symptoms, reduce negative emotions, and improve quality of life.

Objective:To explore the factors associated with severe bleeding after percutaneous nephrolithotomy (PCNL) in male patients and evaluate the efficacy of interventional embolization.Methods:A retrospective case series study was conducted at Nankai Hospital of Tianjin, China, from January 2018 to October 2021. The clinical data of 230 male patients with upper urinary tract stones were analyzed. The observation indicators included age, hypertension, diabetes, renal function abnormalities, history of preoperative anticoagulant use, stone size, stone type, number of puncture channels, operation time and degree of hydronephrosis. To describe the clinical characteristics of bleeding after percutaneous nephrolithotomy in men, and analyze the factors associated with severe bleeding after PCNL. Single factor analysis was performed using the Chi-square ( χ2) test, and multivariate analysis was performed using logistic regression analysis. Results:Univariate analysis showed that diabetes mellitus ( χ2=4.90, P=0.027), abnormal renal function ( χ2=18.32, P<0.001), history of preoperative oral anticoagulants ( χ2=5.10, P=0.024), abnormal bleeding and coagulation function ( χ2=8.22, P=0.004) and the number of puncture channels ( χ2=22.08, P<0.001) were the related factors affecting bleeding after PCNL. Multivariate logistic regression analysis showed that diabetes mellitus ( P=0.032), abnormal renal function ( P<0.001), and the number of puncture channels ( P<0.001) were the independent risk factors of bleeding after PCNL. Of the 28 patients with bleeding after PCNL, 25 were treated with interventional embolization, with a technical success rate of 100.0% and a clinical success rate of 89.3%. Conclusions:For patients with renal calculi and comorbid diabetes, renal function abnormalities, and multiple punctures, relevant preventive measures should be actively administered before PCNL to reduce the risk of postoperative bleeding. For patients with severe bleeding of the kidney after PCNL, TAE is a safe and effective minimally invasive treatment method.

There are a large number of atypical symptoms and undifferentiated diseases in general practice, in which sociological factors are deeply involved. So to incorporate social factors into clinical thinking and to interpret disease from the perspective of the patient′s social life will enrich the multidisciplinary medical model and holistic care in general practice. This article shares author′s clinical experience through introducing typical cases, in which the patient′s social life and behavior characteristics played certain roles in disease development. The article also explores a new way from the sociological perspectives to interpret the complex symptoms that are difficult to be explained clinically by biomedicine or psychology.