This study aimed to investigate the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" (GX) on phlegm and blood stasis syndrome (PBSS) rats combining the methods of network pharmacology and experimental verification. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Anhui University of Chinese Medicine (grant number: AHUCM-rats-2021070). Based on the HPLC-Q-TOF-MS analysis and database, 69 chemical constituents of GX and 163 targets of GX for the treatment of phlegm and blood stasis-related cardiovascular diseases were obtained. Then, key targets such as serine/threonine kinase 1 (Akt1), tumor necrosis factor (TNF), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (Tp53) were screened. Pathway analysis showed that the targets of GX in the treatment of phlegm and blood stasis-relate cardiovascular diseases were mainly involved in PI3K/Akt signaling pathway, sphingolipid metabolism, platelet activation, hypoxia inducible factor-1 (HIF-1), ras-proximate-1 (rap1) and other signaling pathways. In addition, molecular docking analysis showed that apigenin, cucurbitacin D, linolenic acid and kaempferol and other key components had potential binding ability with Akt1, TNF, IL6, VEGFA and Tp53. In the animal experiments, compared to the phlegm and blood stasis syndrome group, GX could significantly improve the traditional Chinese medicine syndrome score, blood lipid, vascular endothelial structure disorders and reduce serum endothelin-1 (ET-1) level, increase serum nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) levels, which could restore aortic endothelial function. In addition, the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aorta could be significantly reduced, which could improve the vascular endothelial injury of aorta. Western blot revealed that GX could significantly decrease the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and Akt in aorta. This study revealed the mechanism of GX in treatment of phlegm and blood stasis-relate cardiovascular diseases is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. In addition, this study also clarified that the reversal of pathological of phlegm and blood stasis syndrome rats may be related to GX inhibiting PI3K/Akt signaling pathway, which could improve vascular inflammation and vascular endothelial function injury.

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

BACKGROUND: Colorectal cancer (CRC) is the fourth cause of cancer death in China. We aimed to provide national and subnational estimates and changes of CRC premature mortality burden during 2005-2020. METHODS: Data from multi-source on the basis of the national surveillance mortality system were used to estimate mortality and years of life lost (YLL) of CRC in the Chinese population during 2005-2020. Estimates were generated and compared for 31 provincial-level administrative divisions in China. RESULTS: Estimated CRC deaths increased from 111.41 thousand in 2005 to 178.02 thousand in 2020; age-standardized mortality rate decreased from 10.01 per 100,000 in 2005 to 9.68 per 100,000 in 2020. Substantial reduction in CRC premature mortality burden, as measured by age-standardized YLL rate, was observed with a reduction of 10.20% nationwide. Marked differences were observed in the geographical patterns of provincial units, and they appeared to be obvious in areas with higher economic development. Population aging was the dominant driver which contributed to the increase in CRC deaths, followed by population growth and age-specific mortality change. CONCLUSIONS Substantial discrepancies were observed in the premature mortality burden of CRC across China. Targeted considerations were needed to promote a healthy lifestyle, expand cost-effective CRC early screening and diagnosis, and improve medical treatment to reduce CRC mortality among high-risk populations and regions with inadequate healthcare resources.
China/epidemiology* ; Colorectal Neoplasms ; Humans

Objective To describe the trend of lung cancer mortality in Xuanwei City,Yunnan Province,from 1990 to 2016 and provide scientific evidence for the prevention and control of lung cancer in Xuanwei.Methods Mortality data from the 2nd(year 1990-1992)and 3rd(year 2004-2005)Retrospective Survey on Causes of Death,and the Routine Death Registration System(year 2011-2013 and 2014-2016)in Xuanwei were used in this study.We calibrated the missing report of the mortality data for the corresponding periods,calculated the crude mortality rates,standardized mortality rates and corresponding 95% of different types of lung cancers in the above four periods.Results The crude mortality rates of all lung cancers in Xuanwei for these four periods(1990-1992,2004-2005,2011-2013,and 2014-2016)were 34.0/100 000,89.8/100 000,102.3/100 000 and 87.2/100 000 respectively.The standardized morality rate of lung cancer remain high in Xuanwei although it has been decreasing since 2004.Morality rates of lung cancer for most age groups showed decreasing trends.The decrease has been statistically significant in the ≤ 40 year group since 2014.Except for Longchang,the standardized mortality rates have decreased in all other townships with high lung cancer prevalence.Conclusions Although the mortality rate of lung cancer remains high in Xuanwei,it has shown a decreasing trend since 2004.The decrease in lung cancer mortality in populations younger than 40 years is statistically significant.
China ; Humans ; Lung Neoplasms ; mortality ; Prevalence ; Retrospective Studies ; Risk Factors

Liriope (Liliaceae) species have been used as folk medicines in Asian countries since ancient times. From Liriope plants (8 species), a total of 132 compounds (except polysaccharides) have been isolated and identified, including steroidal saponins, flavonoids, phenols, and eudesmane sesquiterpenoids. The crude extracts or monomeric compounds from this genus have been shown to exhibit anti-tumor, anti-diabetic, anti-inflammatory, and neuroprotective activities. The present review summarizes the results on phytochemical and biological studies on Liriope plants. The chemotaxonomy of this genus is also discussed.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Flavonoids ; pharmacology ; Humans ; Hypoglycemic Agents ; pharmacology ; Liriope Plant ; chemistry ; Medicine, Traditional ; Neuroprotective Agents ; pharmacology ; Phenols ; pharmacology ; Phytotherapy ; Plant Extracts ; pharmacology ; Saponins ; pharmacology ; Sesquiterpenes ; pharmacology

OBJECTIVETo evaluate the biological effect on the synthesis of the extracellular matrix (ECM) in the cultivation of adult degenerative nucleus pulposus cells using the stiring microcarrier system in vitro.

METHODSThirty-four specimens were collected after intervertebral fusion operations of the patients with intervertebral disc herniation diseases from September 2005 to May 2009. The specimens were then randomly allocated into 2 groups for in vitro cultivation: monolayer culture group and microcarrier culture group. On the exponential phase, SP-ABC immunohistochemical staining and Western blot quantitative analysis were conducted in the two groups to detect the collagen type I and II. Proteoglycan contents of two groups in different growth phases were detected with (35)S-sulfate incorporation assay.

RESULTThe expressions of collagen type I and II in microcarrier culture group were significantly higher than those in monolayer culture group: SP-ABC immunohistochemical staining (collagen type I: 32.5 ± 4.4 vs. 15.2 ± 1.2, t = 2.871, P < 0.01; collagen type II: 43.6 ± 4.1 vs. 23.1 ± 2.2, t = 2.375, P < 0.05); Western blot quantitative analysis (collagen type I: 0.62 ± 0.08 vs. 0.50 ± 0.06, t = 3.327, P < 0.01; collagen type II: 1.46 ± 0.08 vs. 0.86 ± 0.04, t = 2.453, P < 0.05). Nucleus pulposus cells cultivated in stiring microcarrier system showed significantly increased proteoglycan synthesis than monolayer culture group does on both exponential phase and stationary phase (exponential phase: 34 821 ± 312 vs. 21 046 ± 673, t = 2.134, P < 0.05; stationary phase: 45 134 ± 175 vs. 32 193 ± 713, t = 2.801, P < 0.01).

CONCLUSIONSThe expression of collagen type I, II and proteoglycan of adult degenerative nucleus pulposus cells are positive regulated by the stiring microcarrier system, which can be used in the mass amplification of the adult degenerative nucleus pulposus cells.

Adult ; Aged ; Cell Culture Techniques ; Collagen ; metabolism ; Extracellular Matrix ; metabolism ; Female ; Humans ; Intervertebral Disc ; cytology ; Male ; Middle Aged ; Proteoglycans ; metabolism ; Random Allocation ; Young Adult

OBJECTIVETo explore the appropriate strategies which are suitable for the areas with diverse health and economic resource settings in China by estimating the life outcomes and cost-effectiveness of several cervical cancer screening strategies.

METHODSMarkov model was used to calculate the long-term effectiveness, utility, benefit and cost among screened and unscreened cohorts in rural and urban areas, and then analyses of cost-effectiveness, cost-utility and cost-benefit were performed. The assessed screening strategies were acetic acid of visual inspection combined with Lugol's iodine staining (VIA/VILI), conventional Pap smear and simple HPV DNA testing (careHPV) in rural areas, and conventional Pap smear, simple HPV DNA testing (careHPV), HPV DNA testing (HC2) and liquid-based cytology (LBC) alone or combined with HPV DNA testing (LBC+HC2) in urban areas. We estimated the life outcomes and cost-effectiveness of the above screening strategies at one-year, 3-year and 5-year intervals.

RESULTSAll of the screening strategies were effective to decrease cervical cancer mortality and to increase life years, with a trend of shorter screening interval having better effectiveness. However, no matter in urban or rural areas, compared with careHPV testing at 5-year interval, the costs of other screening strategies were 1.28 - 13.86 folds, 1.31 - 14.14 folds, and 1.27 - 12.80 folds higher to avoid one death, to save a year of life, and a QALY, and the benefit per cost of other screening strategies was 9.9%-90.2%.

CONCLUSIONScareHPV testing at 5-year interval has the best cost-effectiveness performance and the highest benefit-cost ratio with the moderate life outcomes. It is the optimal cervical cancer screening strategy to be generalized in our country. careHPV testing at 3 years interval can be considered in more developed areas to achieve better effectiveness.

Acetic Acid ; Adult ; Cervical Intraepithelial Neoplasia ; diagnosis ; economics ; epidemiology ; virology ; China ; epidemiology ; Cost-Benefit Analysis ; Cytological Techniques ; DNA, Viral ; analysis ; Early Detection of Cancer ; economics ; methods ; Female ; Human Papillomavirus DNA Tests ; Humans ; Iodides ; Markov Chains ; Mass Screening ; economics ; methods ; Middle Aged ; Models, Biological ; Models, Statistical ; Papanicolaou Test ; Quality-Adjusted Life Years ; Rural Population ; Urban Population ; Uterine Cervical Neoplasms ; diagnosis ; economics ; epidemiology ; virology ; Vaginal Smears

OBJECTIVETo clarify the clinical feature, diagnosis and therapy of the pulmonary cryptococcosis (PC).

METHODSA retrospective study of cases with PC who were diagnosed by pathological examinations between January 1996 and December 2010 was conducted. Eighty-one cases were enrolled in the study (58 male and 23 female patients; mean age of (51±11) years). Forty-one cases were asymptomatic at the time of diagnosis. There were single pulmonary lesions in 50 cases, and multiple lesions in 31 cases. Fourteen lesions (17.3%) were located in left upper lobe, 27 (33.3%) in left lower lobe, 21 (25.9%) in right upper lobe, 3 (3.7%) in right middle lobe, 28 (34.6%) in right lower lobe, and 3 (3.7%) diffusely involved bilateral lungs. The tumors ranged from 0.8 to 10.0 cm in diameter with a mean of (2.9±1.8) cm. All the cases were misdiagnosis prior to the surgical resection, and histologically confirmed by postoperative pathological specimens.

RESULTSAll the cases received surgical treatment including complete resection in 69 cases, and palliative resection in 12 cases. Resections were performed by means of video-assisted thoracoscopy in 31 cases and thoracotomy in 50 cases. Surgical resections included pulmonary wedge excisions in 42 cases, and lobectomies in 39 cases. After histological confirmation, 63 cases (77.8%) were treated with antifungal agents, which consisted of fluconazole in 38 cases, itraconazole in 18 cases, amphotericin B in 6 cases, and flucytosine in 4 cases. There were no intraoperative death, but two cases died for cryptococcal meningoencephalitis in the postoperative period. Operative morbidity occurred in 7 (8.6%) cases. The median follow-up was 42.5 months (6 to 84 months). There were 2 local relapses of PC, and 9 cases with complications of anti-fungal agents.

CONCLUSIONSThe clinical manifestations of PC are mild and non-specific, with no characteristic radiographic manifestations. Surgical resection is usually indicated for definite diagnosis and treatment. Antifungal drug therapy is indispensable even after complete resection.

Adult ; Aged ; Antifungal Agents ; therapeutic use ; Cryptococcosis ; diagnosis ; drug therapy ; surgery ; Female ; Follow-Up Studies ; Humans ; Lung ; microbiology ; pathology ; Lung Diseases, Fungal ; diagnosis ; drug therapy ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Young Adult