ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.

Humans ; Albumins ; Albuminuria/urine* ; Blood Pressure ; China/epidemiology* ; Creatinine ; Risk Factors ; Aged

Objective To investigate the pharmacological effects of"Yajieshaba"on mice with alcohol-induced liver injury and to investigate the mechanism of the impact of"Yajieshaba"on the regulation of intestinal flora by 16S rDNA technology.Methods Healthy male KM mice were randomly divided into control,model,"Yajieshaba"low,medium,and high dose(0.39,1.17 and 3.51 g·kg-1)groups and Bifendatatum(2.93 mg·kg-1)groups,with eight mice in each group.After one week of pre-administration of"Yajieshaba",a mouse model of acute alcoholic liver injury was established by a single instillation of 56%alcohol,and the levels of AST and ALT in the serum of mice were measured,and the morphological changes of liver histology were observed by HE staining;secondly,faecal DNA was extracted from each group under aseptic operation,and 16S rDNA sequencing and differential analysis by alpha diversity and species composition at the phylum and genus levels were performed.Results The results showed that the biochemical indexes of liver function(ALT and AST)were significantly improved by"Yajieshaba",and the degree of liver damage was significantly reduced by HE staining.At the phylum level,it significantly decreased the abundance of Aspergillus and increased the quantity of Bacteroides;at the genus level,it significantly up-regulated the plenty of Bacteroides and Prevotella and downregulated a lot of Prevotella and Helicobacter.At the genus level,"Yajieshaba"significantly up-regulated the abundance of Bacillus spp.and Prevotella spp.and down-regulated the abundance of Prevotella spp.and Helicobacter spp.Conclusion"Yajieshaba"may play an anti-acute alcoholic liver injury effect by regulating the intestinal flora and metabolites.

Objective:To analyze the relevant factors affecting postnatal glucose metabolism in pregnant women with gestational diabetes and construct a nomogram prediction model.Methods:Using a retrospective study method, 210 cases of gestational diabetes patients admitted to Danyang People′s Hospital from March 2019 to November 2021 were selected as the study subjects, and they were divided into 125 cases of normal group and 85 cases of abnormal group according to the postnatal glucose metabolism. The predictive value was analyzed using the subject work characteristics (ROC) curve experiment; the risk factors affecting abnormal postpartum glucose metabolism in pregnant women with gestational diabetes mellitus were analyzed using Logistic regression experiment; and the clinical efficacy of the column-line diagram model was verified using internal data.Results:There was no statistically significant difference between the two groups when comparing the general information such as age ( P>0.05); compared with the normal group, the abnormal group had higher values of total cholesterol (TG), postprandial 2 h blood glucose (OGTT 2 h), glycosylated hemoglobin, and pre-pregnancy body mass index (BMI): (4.23 ± 1.35) mmol/L vs. (3.65 ± 1.50) mmol/L, (9.36 ± 1.25) mmol/L vs. (8.20 ± 1.51) mmol/L, (8.31 ± 2.96)% vs. (6.73 ± 2.23)%, (24.96 ± 4.21) kg/m 2 vs. (23.20 ± 3.25) kg/m 2, and those with a family history of diabetes mellitus were higher: 47.06%(40/85) vs. 20.80%(26/125), there were statistical differences ( P<0.05); the area under the curve (AUC) of TG, OGTT 2 h, glycated hemoglobin, and pre-pregnancy BMI were 0.605, 0.720, 0.670, and 0.616, with optimal cut off values of 4.65 mmol/L, 8.33 mmol/L, 8.06%, and 25.27 kg/m 2; TG (>4.65 mmol/L), OGTT 2 h (>8.33 mmol/L), glycated hemoglobin (>8.06%), and preconception BMI (>25.27 kg/m 2), and family history of diabetes mellitus (yes) were risk factors for abnormal glucose metabolism in pregnant women ( P<0.05); the C-index of the risk of postpartum glucose metabolism in pregnant women with gestational diabetes mellitus predicted by the column chart model was 0.750 (95% CI 0.672 - 0.864). The model predicted that the threshold of the risk of postnatal glucose metabolism in pregnant women with gestational diabetes mellitus was >0.07. Conclusions:TG (>4.65 mmol/L ), OGTT 2 h (>8.33 mmol/L ), glycated haemoglobin (>8.06%), pre-pregnancy BMI (>25.27 kg/m 2), and family history of diabetes (yes) are risk factors for abnormal glucose metabolism in pregnant women, and the model constructed based on the variables have good predictive power.

Objective:To analyze the composition and clinical characteristics of urinary calculi in infants in Xinjiang.Methods:The clinical data of 75 infants with urinary calculi admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2021 were retrospectively analyzed, including the general situation of the children, stone-related parameters, random urine pH value, urine culture and biochemical examination results. The serum uric acid, serum calcium, urine pH value, positive rate of urine culture, and stone length between infants with and without ammonium urate stones were compared. Measurement data conforming to normal distribution were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for inter-group comparison. Measurement data that did not conform to the normal distribution were expressed as the median (interquartile distance) [ M ( Q1, Q3)], and Mann-Whitney U test was used for comparison between groups. The Chi-square test, continuity-corrected Chi-square test or Fisher exact probability method were used for the comparison of count data. Results:The median age of infants with urinary calculi was 23.04 months, and the ratio of male to female was 3.2∶1. More than half of the infants (81.3%, 61/75) came from rural areas, 57.3% (43/75) were malnourished, 33.3% (25/75) were complicated with urinary tract infection, and 8.0% (6/75) were combined with urinary system congenital malformation. The calculi were found in 53 cases (70.67%) of kidney, 27 cases (36.0%) of ureter, 17 cases (22.67%) of urethra and 16 cases (21.33%) of bladder. The analysis of calculi composition showed that there were 44 cases (58.67%) of ammonium urate, 39 cases (52.0%) of calcium oxalate, 14 cases (18.67%) of apatite carbonate and 7 cases (9.33%) of uric acid. Kidney calculi was more common in female infants ( P=0.011). Compared with the infant group ( n=19), calcium oxalate stones were more common in the preschooler group ( n=56) ( P=0.039), but there were not statistical difference in the incidence of ammonium urate, apatite carbonate and uric acid stones. There were not statistical difference in gender, age, place of residence, nutritional status, serum uric acid, serum calcium, urine pH value, positive rate of urine culture, stone maximum diameter and incidence of bladder stones between ammonium urate group and non-ammonium urate group. Conclusions:The incidence of urinary calculi in infants is higher in boys, and the most common site of calculi is the upper urinary tract, especially in female kidney calculi. Ammonium urate is the main component of urinary calculi in infants. Calcium oxalate stones are more common in preschooler group. Infants with urinary calculi are mostly rural residents, and malnutrition and urinary tract infection are more common.

【Objective】 To analyze the clinical characteristics of children with ammonium urate stones in Xinjiang, so as to provide reference for the prevention and treatment of this disease. 【Methods】 The clinical data of all children with ammonium urate stones admitted to the People’s Hospital of Xinjiang Uygur Autonomous Region from 2016 to 2021 were retrospectively analyzed, including age, sex, body mass index, stone site, stone size, stone component, urine pH, urine culture and biochemical examination results. The serum total protein, albumin, sodium, potassium, calcium, magnesium, uric acid and urine pH were compared between the pure and mixed groups. 【Results】 A total of 61 children (31.6%) had ammonium urate stones, their average age was (4.05±3.37) years, and the male to female ratio was 2.21∶1. Among them, there were 37 cases (60.7%) of renal calculi and 50 cases (82.0%) of upper urinary calculi. The most common component of mixed ammonium urate stones was calcium oxalate, including calcium oxalate monohydrate, calcium oxalate monohydrate and calcium oxalate dihydrate. Compared with mixed type, children with pure stone type had a younger age (P=0.001) and a smaller stone size (P=0.003). Positive urine culture was detected in 14 cases (23.0%), 7 of which (50% were infected with Escherichia coli, and 11 (78.6%) with non-urease bacteria. 【Conclusion】 Non-urease bacteria are the main pathogens of urinary tract infection in children with ammonium urate stones. The incidence is higher in boys, and the most common stone location is upper urinary tract. Calcium oxalate is the most common mixed component. Pure type is more common in young children and the stones are relatively small.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.

Objective:Health policy and management, and its development as a discipline, play an important role in promoting the development of medicine; however, where is no scientific and reasonable evaluation system of science and technology in practice.Here we will explore and establish a special evaluation system to this research feild.Methods:To analyze the problems, tasks and unique research methods specially solved and used in the field of health management and policy; to discuss the existing problems with theory combined with practice.Results:According to the guidance of national policy, put forward principles and some assessment indicators with their weight grading, index, and examples in detail for the academic evaluation system in the field of this field.Conclusions:Health policy and management is a kind of discipline of the category of social science that possesed the particularity of practice management. Thus, it is important that the academic evaluation should reflect the responsibilities, contributions and characteristics of this subject and the researchers.

Objective: To explore the activity of auranofin against ovarian cancer cells and its possible molecular mechanism． Methods : The dose-response survival curve and IC50 of auranofin on ovarian cancer cell lines ，SKOV3，Caov3 and SW626 cells and immortalized normal human embryonic kidney HEK-293T cells were determined by CCK-8 method．Cell cycle was determined by flow cytometry．The levels of total glutathione ( GSH) ，reduced GSH and glutathione disulfide ( GSSG) ，thioredoxin reductase (TrxR) and reactive oxygen species (ROS) in cells were determined by microplate reader，and the reduced GSH / GSSG ratio was calculated．Western blot was used to determine the expression of cyclin dependent kinases( CDK) 4，CDK6，Cyclin D1，P53，p-P53 and MDM2 in SKOV3 and Caov3 ovarian cancer cells. Results : Compared with HEK-293T cells，the dose-response survival curves and IC50 values of SKOV3，Caov3 and SW626 cells showed that ovarian cancer cells were more sensitive to auranofin (P＜0. 05) ．After SKOV3 and Caov3 cells were treated with the dose of respective IC50 concentrations of auranofin，compared with the untreated cells group，the Auranofin IC50 group cells' intracellular levels of GSH，the ratio of reduced GSH / GSSG and the activity of TrxR decreased (t = 25. 11 /31. 18，14. 72 /19. 92，43. 30 /10. 74， all P＜0. 05) ，and the levels of ROS increased (t = 23. 82 /27. 71，P＜0. 05) ; cells number at G0 / G1 phases increased，with cells number at S and G2 phases decreased (P＜0. 05) ; and the expression levels of cell cycle-related proteins CDK4，CDK6，Cyclin D1 and the P53-specific E3 ubiquitin ligase MDM2 were down-regulated (t = 7. 51 /15. 59，17. 32 /11. 26，20. 78 /20. 78，24. 25 /17. 32，all P＜0. 05) ，while the expression levels of P53 and p-P53 were up-regulated (t = 17. 32 /24. 25，12. 12 /10. 39，all P ＜0. 05) ． Conclusion Auranofin causes oxidative stress in ovarian cancer cells by inhibiting TrxR activity，and by partially degrading MDM2 to stabilize and acti- vate P53，so as to block the cancer cells in G0 / G1 phase，and exert anti-ovarian cancer activities.