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.

To determine the main components of the fishy smell of the Eupolyphaga Steleophaga, and to provide a theoretical basis for deodorizing the Eupolyphaga Steleophaga. METHODS Head space-solid phase microextraction-gas chromatography-mass spectrometry was used to identify the components of 10 batches of Eupolyphaga Steleophaga, and area normalization method and chemometrics method were used to analyze the smelly gas of different batches. Odor activity value(OAV) was used to evaluate the contribution of odor components and identify key odor components. RESULTS A total of 87 volatile odor components were identified, the key fishy smell compounds(OAV≥1) were m-methylphenol, dimethyltrisulfide, 4-methylphenol, 2-methyliso-borneol, 2-etzol, 4-methylvaleric acid, iso-valeric acid, etc. Modified fishy gas composition(0.1

OBJECTIVE To develop a DNA authenticity identification kit of Gastrodia elata that combined DNA extraction technology with PCR technology, and to evaluate the performance of the kit methodologically. METHODS The ITS2 sequences of Gastrodia elata and its common forgeries, such as amabilis root, dahlia tuber and potato, were found by the National Center for Biotechnology Information(NCBI). DNAMAN was used for multi-sequence alignment, and NCBI-primer-blast was used to design specific primers of Gastrodia elata. Improved DNA extraction method to ensure efficient extraction of authentic Gastrodia elata and its common forgeries genomic DNA, UV spectrophotometry was used to measure the concentration and purity. The PCR reaction system was optimized, the composition and reaction conditions of the kit were determined, and the commercially available gastrodia elata samples were randomly sampled. RESULTS The DNA purity OD260/OD280 values of the samples extracted by the developed kit were (1.87±0.13). The minimum detection limit was 10 ng·μL−1, and the result of repeated detection was the same for 3 times. Repeated freezing and thawing for 5, 10, 15, 20 times had no effect on the detection effect, and it could be stored at −20℃ for 1 year, among 10 commercially available gastrodia elata samples tested, 7 were authentic and 3 were counterfeit. CONCLUSION The DNA authenticity test kit is highly specific, sensitive, reproducible and stable, and the test results are accurate, it is suitable for the rapid identification of asparagus and its common forgeries.

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.

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 It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P＜0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P＜0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P＜0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P＜0.05), but the differences in Chao1 index were not statistically significant (P＞0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P＞0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P＜0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P＜0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.