Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province.Methods:Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ2 Inspection. Results:A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old ( χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) ( χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath ( χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old ( χ2=9.74, P<0.001), while RSV is more common in children under 1 year old ( χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old ( χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak ( χ2=252.68, P<0.001). Conclusion:The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Objective:To discuss the damage effect of vesicular stomatitis virus(VSV)on the vascular endothelial(VE)barrier,and to clarify its mechanism.Methods:The canine kidney cells were used to amplify VSV.The half tissue culture infective dose(TCID50)of VSV was determined using mouse brain endothelial tumor bEnd.3 cells,and subsequent experiment was conducted using 300 times the TCID50.The bEnd.3 cells were divided into infection 0 h group,infection 4 h group,infection 8 h group,and infection 12 h group for VE barrier damage experiments due to VSV infection.The bEnd.3 cells were also divided into control group,infection group,and correction group for experiments to inhibit the VSV replication and restore the VE barrier.The bEnd.3 cells were inoculated into Transwell chambers to construct an in vitro VE barrier model.Cell voltage resistance meter was used to detect the transepithelial resistance(TER)in various groups after the bEnd.3 cells were infected with VSV at different time points;fluorescein isothiocyanate-dextran leakage assay was used to detect the permeability coefficients of the cells in various groups;immunofluorescence staining was used to observe the localization changes of VE-cadherin,β-catenin,and phosphorylated β-catenin(p-β-catenin)in cytoskeleton and adherens junctions(AJs)of the bEnd.3 cells after VSV infection;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Wnt and β-catenin mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Wnt,β-catenin,and p-β-catenin proteins in the cells in various groups.Results:The TCID50 of VSV was 10-4.5·100 μL-1.TheTranswell chamber experiment results showed that compared with infection 0 h group,the TERs in the cells in the other groups were significantly decreased(P＜0.05),and the permeability coefficients were significantly increased(P＜0.05).The immunofluorescence staining results showed that compared with control group,the cytoskeleton of the bEnd.3 cells in infection group was disordered,the cell gaps was increased,the linear index of AJs was significantly decreased(P＜0.05),and β-catenin and p-β-catenin translocated from the cell membrane to the perinuclear area.The RT-qPCR results showed that compared with infection 0 h group,the expression levels of Wnt mRNA in the cells in the other groups were significantly decreased(P＜0.05),while the expression levels of β-catenin mRNA showed no statistically significant difference(P＞0.05).The Western blotting results showed that compared with infection 0 h group,the expression levels of Wnt protein in the cells in the other groups were significantly decreased(P＜0.05),the expression levels of β-catenin showed no statistically significant differences(P＞0.05),and the expression levels of p-β-catenin were significantly increased(P＜0.05).After inhibiting the VSV replication and correcting the low density lipoprotein receptor(LDLR)abnormalities,the Transwell chamber experiment results showed that compared with infection group,the TER in the cells in correction group was significantly increased(P＜0.05),and the permeability coefficient was significantly decreased(P＜0.05).The immunofluorescence staining results showed that compared with infection group,the gaps in the cells in correction group were reduced,and the perinuclear aggregation of β-catenin and p-β-catenin in the cells was restrained.The RT-qPCR results showed that compared with infection group,the expression level of Wnt mRNA in the cells in correction group was significantly increased(P＜0.05).The Western blotting results showed that compared with infection group,the expression level of Wnt protein in the cells in correction group was significantly increased(P＜0.05),the expression level of β-catenin showed no statistically significant difference(P＞0.05),and the expression level of p-P-catenin was significantly decreased(P＜0.05).Conclusion:VSV infection can cause the LDLR inactivation,reduce the expression level of Wnt protein,increase the phosphorylation level of β-catenin and cause its internalization,disrupt the stability of AJs,and ultimately lead to VE barrier damage.

Placental diseases may affect the outcome of pregnancy and long-term health of the mother and fetus. Fetal fraction is a key indicator for the success of non-invasive prenatal testing, and has been associated with gestational age, body mass index and fetal chromosomal aneuploidies. Many studies have found that fetal fraction is also related to placenta-derived diseases and may become a new predictor for such diseases. This article has summarized the association between the two, with an aim to provide new ideas for the prediction of placental diseases.

Objective:To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province.Methods:Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ2 Inspection. Results:A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old ( χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) ( χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath ( χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old ( χ2=9.74, P<0.001), while RSV is more common in children under 1 year old ( χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old ( χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak ( χ2=252.68, P<0.001). Conclusion:The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

Objective:To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments).Methods:A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed.Results:Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment ( P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments ( P＜0.001). Conclusions:Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.