According to the latest 2022 Global Cancer Burden report released by the World Health Organization's International Agency for Research on Cancer,the number of newly diagnosed cancer patients worldwide continues to rise,and this trend is expected to become more pronounced by 2050.In the same year,China's cancer incidence report for 2022 revealed that both the number of new cancer cases and cancer-related deaths have continued to increase compared to previous years,indicating a worrying situation.Amid the growing demand for effective cancer therapies,the development of anti-cancer drugs is gaining significant momentum.Traditional Chinese Medicine(TCM)has begun to play an increasingly prominent role in the anti-cancer drug market,contributing a unique"Chinese solution"to global cancer treatment.However,TCM is characterized by its multi-component,multi-pathway,and multi-target nature,making it challenging to comprehensively study its anti-cancer mechanisms using traditional research models.Consequently,there is an urgent need to develop new research models that align with the characteristics of TCM.Organoids,as an emerging technology and an ideal preclinical model for human diseases,address the limitations of traditional disease models in TCM research.Their application in the study of TCM's anti-cancer effects is rapidly expanding.This article reviews and summarizes the use of organoid technology in TCM-based anti-cancer research,analyzing its advantages,limitations and developmental trends.

Objective:To compare the sustained virological response (SVR) and viral recurrence in patients with chronic hepatitis C (CHC) after antiviral treatment, and to further analyze the influencing factors of liver-related events (LRE).Methods:This was a retrospective cohort study. A total of 1 844 CHC patients who visited the Department of Infectious Diseases of Hainan General Hospital from January 1st, 2013 to December 31st, 2022 were included. After screening, 891 patients were selected and divided into direct-acting antiviral agent (DAA) treatment group, interferon treatment group and non-antiviral treatment group based on different intervention measures. Propensity score matching was performed, and SVR and viral recurrence were compared among the three groups. Statistical analysis was performed using the chi-square test, and multivariate Cox regression analysis was used to evaluate the risk factors for LRE.Results:The confirmed CHC patients showed an increasing trend year by year (average annual change percentage=19.97%, 95% confidence interval ( CI) 10.46% to 30.30%, t=4.32, P<0.001). After propensity score matching, the total sample size of 891 CHC patients was 451, including 100 in the interferon treatment group, 311 in the DAA treatment group, and 40 in the non-antiviral treatment group. In the interferon treatment group, 89 cases (89.00%) achieved SVR and nine cases (9.00%) had recurrence. In the DAA treatment group, 306 cases (98.39%) achieved SVR and 10 cases (3.22%) had recurrence. The differences were statistically significant ( χ2=17.84 and 6.22, respectively, both P<0.05). Cox multivariate regression analysis showed that age (hazard ratio ( HR)=1.065, 95% CI 1.028 to 1.104, P<0.001), alcohol consumption ( HR=3.034, 95% CI 1.302 to 7.071, P=0.010) were independent risk factors for LRE in CHC patients, while albumin ( HR=0.858, 95% CI 0.802 to 0.917, P<0.001), DAA treatment ( HR=0.267, 95% CI 0.103 to 0.692, P=0.007) were protective factors. In CHC patients receiving antiviral treatment, diabetes ( HR=6.719, 95% CI 2.242 to 20.137, P<0.001), total bilirubin ( HR=1.111, 95% CI 1.054 to 1.171, P<0.001) and viral recurrence ( HR=4.646, 95% CI 1.322 to 16.321, P=0.017) were independent risk factors for LRE. Conclusions:Compared with interferon treatment, DAA treatment has a significantly higher SVR rate and a lower recurrence rate. Age and alcohol consumption are independent risk factors for LRE, while higher albumin levels and DAA treatment are protective factors. In CHC patients receiving antiviral treatment, diabetes, viral recurrence, and total bilirubin are independent risk factors for LRE.

Objective To investigate the association between gut microbiota metabolite,trimethy-lamine-N-oxide(TMAO),and total imaging burden in diabetic patients with cerebral small vessel disease(CSVD).Methods A prospective study was conducted on 112 elderly diabetic patients with CSVD admitted in our hospital from June 2022 to May 2024.According to the total imaging burden score,they were divided into a high burden group(burden score≥2,57 cases)and a low burden group(burden score＜2,55 cases).High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry was applied to detect the plasma level of TMAO.Then based on the tertile of plasma TMAO level,the patients were also assigned into low(＜2.44 μmol/L,38 cases),median(2.44 μmol/L≤TMAO＜5.18 μmol/L,37 cases)and high TMAO(≥5.18 μmol/L,37 cases)groups.ROC curve analysis was used to assess the predictive value of plasma TMAO level for high imaging burden in diabetic patients with CSVD.Binary logistic regression analysis was employed to analyze the correlation between plasma TMAO level and high imaging burden.Results The high burden group exhibited significantly higher plasma TMAO level than the low burden group(P=0.002).The AUC value of plasma TMAO level in predicting high imaging burden was 0.669(95％CI:0.569-0.769,P=0.002).The percentage of high imaging burden was 34.2％,54.1％and 64.9％,respectively among the low,median and high TMAO groups,with significant differences among them(Chi-square=7.270,P=0.026).Binary logistic regression analysis indicated the correlation between TMAO and high imaging burden(OR=1.178,95％CI:1.019-1.364,P=0.027).Conclusion In elderly diabetic patients with CSVD,plasma TMAO level is closely associated with high imaging burden,with higher TMAO level,higher risk for high imaging burden.

According to the latest 2022 Global Cancer Burden report released by the World Health Organization's International Agency for Research on Cancer,the number of newly diagnosed cancer patients worldwide continues to rise,and this trend is expected to become more pronounced by 2050.In the same year,China's cancer incidence report for 2022 revealed that both the number of new cancer cases and cancer-related deaths have continued to increase compared to previous years,indicating a worrying situation.Amid the growing demand for effective cancer therapies,the development of anti-cancer drugs is gaining significant momentum.Traditional Chinese Medicine(TCM)has begun to play an increasingly prominent role in the anti-cancer drug market,contributing a unique"Chinese solution"to global cancer treatment.However,TCM is characterized by its multi-component,multi-pathway,and multi-target nature,making it challenging to comprehensively study its anti-cancer mechanisms using traditional research models.Consequently,there is an urgent need to develop new research models that align with the characteristics of TCM.Organoids,as an emerging technology and an ideal preclinical model for human diseases,address the limitations of traditional disease models in TCM research.Their application in the study of TCM's anti-cancer effects is rapidly expanding.This article reviews and summarizes the use of organoid technology in TCM-based anti-cancer research,analyzing its advantages,limitations and developmental trends.

Objective To investigate the association between gut microbiota metabolite,trimethy-lamine-N-oxide(TMAO),and total imaging burden in diabetic patients with cerebral small vessel disease(CSVD).Methods A prospective study was conducted on 112 elderly diabetic patients with CSVD admitted in our hospital from June 2022 to May 2024.According to the total imaging burden score,they were divided into a high burden group(burden score≥2,57 cases)and a low burden group(burden score＜2,55 cases).High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry was applied to detect the plasma level of TMAO.Then based on the tertile of plasma TMAO level,the patients were also assigned into low(＜2.44 μmol/L,38 cases),median(2.44 μmol/L≤TMAO＜5.18 μmol/L,37 cases)and high TMAO(≥5.18 μmol/L,37 cases)groups.ROC curve analysis was used to assess the predictive value of plasma TMAO level for high imaging burden in diabetic patients with CSVD.Binary logistic regression analysis was employed to analyze the correlation between plasma TMAO level and high imaging burden.Results The high burden group exhibited significantly higher plasma TMAO level than the low burden group(P=0.002).The AUC value of plasma TMAO level in predicting high imaging burden was 0.669(95％CI:0.569-0.769,P=0.002).The percentage of high imaging burden was 34.2％,54.1％and 64.9％,respectively among the low,median and high TMAO groups,with significant differences among them(Chi-square=7.270,P=0.026).Binary logistic regression analysis indicated the correlation between TMAO and high imaging burden(OR=1.178,95％CI:1.019-1.364,P=0.027).Conclusion In elderly diabetic patients with CSVD,plasma TMAO level is closely associated with high imaging burden,with higher TMAO level,higher risk for high imaging burden.

Objective:To compare the sustained virological response (SVR) and viral recurrence in patients with chronic hepatitis C (CHC) after antiviral treatment, and to further analyze the influencing factors of liver-related events (LRE).Methods:This was a retrospective cohort study. A total of 1 844 CHC patients who visited the Department of Infectious Diseases of Hainan General Hospital from January 1st, 2013 to December 31st, 2022 were included. After screening, 891 patients were selected and divided into direct-acting antiviral agent (DAA) treatment group, interferon treatment group and non-antiviral treatment group based on different intervention measures. Propensity score matching was performed, and SVR and viral recurrence were compared among the three groups. Statistical analysis was performed using the chi-square test, and multivariate Cox regression analysis was used to evaluate the risk factors for LRE.Results:The confirmed CHC patients showed an increasing trend year by year (average annual change percentage=19.97%, 95% confidence interval ( CI) 10.46% to 30.30%, t=4.32, P<0.001). After propensity score matching, the total sample size of 891 CHC patients was 451, including 100 in the interferon treatment group, 311 in the DAA treatment group, and 40 in the non-antiviral treatment group. In the interferon treatment group, 89 cases (89.00%) achieved SVR and nine cases (9.00%) had recurrence. In the DAA treatment group, 306 cases (98.39%) achieved SVR and 10 cases (3.22%) had recurrence. The differences were statistically significant ( χ2=17.84 and 6.22, respectively, both P<0.05). Cox multivariate regression analysis showed that age (hazard ratio ( HR)=1.065, 95% CI 1.028 to 1.104, P<0.001), alcohol consumption ( HR=3.034, 95% CI 1.302 to 7.071, P=0.010) were independent risk factors for LRE in CHC patients, while albumin ( HR=0.858, 95% CI 0.802 to 0.917, P<0.001), DAA treatment ( HR=0.267, 95% CI 0.103 to 0.692, P=0.007) were protective factors. In CHC patients receiving antiviral treatment, diabetes ( HR=6.719, 95% CI 2.242 to 20.137, P<0.001), total bilirubin ( HR=1.111, 95% CI 1.054 to 1.171, P<0.001) and viral recurrence ( HR=4.646, 95% CI 1.322 to 16.321, P=0.017) were independent risk factors for LRE. Conclusions:Compared with interferon treatment, DAA treatment has a significantly higher SVR rate and a lower recurrence rate. Age and alcohol consumption are independent risk factors for LRE, while higher albumin levels and DAA treatment are protective factors. In CHC patients receiving antiviral treatment, diabetes, viral recurrence, and total bilirubin are independent risk factors for LRE.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective To compare the predictive value of Fried frailty phenotype (FP) and Tilburg frailty Index (TFI) to the quality of life in community elderly people so as to provide a reference for the grass-roots general practitioners to choose the appropriate quality of life screening tool in the community elderly people.Methods Using the convenient sampling method,638 elderly people in the community were selected as the research subjects.FP and TFI were used to assess frailty,and the quality of life was evaluated by the brief health questionnaire (SF-12).The Kappa value was used to evaluate the consistency of the two scales. The Pearson correlation was used to detect the correlation between the two scales and SF-12 respectively,and the Bayes discriminant analysis was used to evaluate and analyze the predictive ability of the two scales on the quality of life.Results Among the 638 community elderly people,the screened incidence rate of frailty was 15.4％ by FP and 28.2％ by TFI,the Kappa value of FP and TFI consistence test was 0.569 (P<0.001). The results of correlation analysis showed that FP and TFI were negatively correlated with the total physical health score (PCS) and total mental health score (MCS) of SF-12 (FP with PCS and MCS,r=-0.772,-0.349,P<0.01;TFI with PCS and MCS,r=-0.738,-0.491,P<0.01).Taking the quality of life as the criterion,the cross-validation accuracy rates of FP and TFI for predicting the PCS decline were 76.65％ and 71.63％ respectively,which for MCS decline was 72.10％ and 75.55％ respectively.Conclusion Both FP and TFI all have the predictive value on the decline of quality of life of the community elderly people,but TFI has the characteristics of multi-dimensions and easy application,so it is more effective and practical for evaluating the quality of life in the community elderly people.

Objective To retrospectively analyze of factors influencing early preterm birth(EPB)and late preterm birth(LPB)in pregnancy women with placenta previa complicated by placenta accreta spectrum disorders(PAS),and assess maternal and infant outcomes.Methods We included 590 cases of pregnancy women with placenta previa complicated by PAS who underwent cesarean sections at five hospitals in Wuhan and Xianning cities between January 2018 and June 2021.These patients were divided into three groups based on delivery gesta-tional age:EPB,LPB,and term birth(TB).A multiple logistic regression model was employed to analyze the risk factors associated with EPB and LPB.Additionally,differences in early maternal and infant outcomes among these groups were examined.Results Among 590 pregnancy women with placenta previa complicated by PAS,the proportions of EPB and LPB were 9.7%and 54.4%.The use of uterine contraction inhibitors prior to cesarean section,vaginal bleeding,and previous cesarean sections history were identified as risk factors for both EPB and LPB.The proportion of severe postpartum hemorrhage was comparable between the EPB group and the LPB group;however,the incidence of neonatal asphyxia,low birth weight infants,and the rate of newborns transferred to the Neonatal Intensive Care Unit(NICU)within 24 hours after cesarean delivery were significantly higher in the EPB group compared to the LPB group.Conclusions Placenta previa complicated by PAS predominantly leads to LPB.The history of prior cesarean sections,uterine contractions,and vaginal bleeding prior to cesarean section,are sig-nificantly associated with both EPB and LPB.During the perinatal period,efforts should be made to extend gesta-tional weeks under close monitoring to minimize the incidence of premature births and thereby improve early mater-nal and infant outcomes.

Fibrous dysplasia of bone (FD) is a tumorlike disease characterized by intramedullary fibrosis, in which the development of the bone in the lesion area stops at the stage of immature braided bone, with the inability to form a normal bone trabecula, resulting in structural changes and reduced mechanical strength of the bone. Repeated pathological fractures often occur with weight bearing, followed by curvature of the affected bone, limb shortening, and abnormal gait. The proximal femur is often involved in FD limb malformations, with complex types and degrees, most of which are manifested as gradually aggravating hip varus and diaphysial curvature. The proximal femur is a common site of limb deformity caused by FD, the types and severity of malformations are complex and varied, which is usually manifested as gradually aggravated varus hip joint and diaphysis bending deformity. The purpose of deformity correction is to restore the normal mechanical axis and length of the femur, thereby restoring the function of the limb, avoiding the progression of deformity and relieving the pain symptoms caused by repeated pathological microfractures, which is more important than the treatment of the lesion itself. The preoperative treatment plan should be made individually for each patient according to the location and extent of the lesion and the type of the lesion. The patients need to be followed up for a long time to adjust the correction plan. Whether the lesion should be curette and bone graft and the type of bone graft material used are still controversial. The femoral deformity of FD should be analyzed based on the principles of deformity correction, the type of deformity and the location of the apex of the deformity should be determined, the osteotomy plan should be designed, and the preoperative simulation should be performed. Both intramedullary and extramedullary fixation after osteotomy can provide sufficient biological stability. The choice of fixation device should be determined according to the specific situation during the operation. There is no obvious abnormality in bone healing and regeneration in FD patients, but dysplastic bone tissue is included in the callus formation. The limb deformity of FD patients is prone to relapse after treatment, long-term close follow-up is needed to adjust the correction plan.