Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head / 中国修复重建外科杂志

OBJECTIVE@#To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms.@*METHODS@#Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH.@*RESULTS@#Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent.@*CONCLUSION@#At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

Establishment and evaluation of in vitro galectin-3 inhibitor screening model / 药学学报

Galectin-3 (Gal-3) belongs to the galectin family and is specific in binding β-galactoside. Through its C-terminal domain, Gal-3 binds to the galactoside group of the glycosylated insulin receptor (IR) and inhibits IR signaling pathway, which leads to the insulin resistance. Thus, Gal-3 is a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. Here we report a simple Gal-3 screening model based on the property that Gal-3 binds to the galactoside. We expressed and purified human Gal-3 in Escherichia coli (E.coli), and labeled it with fluorescein isothiocyanate (FITC) in vitro. After incubating FITC labeled Gal-3 (Gal-3-FITC) with PANC-1 cells, which express glycosylated membrane protein, PANC-1 cells started to show green fluorescent signal due to the Gal-3-FITC binding to the glycosylated membrane protein. Gal-3 inhibitor disrupts the binding of Gal-3-FITC and PANC1 cells, subsequently leads to the decrease of the fluorescent signal in PANC-1 cells. We can evaluate the inhibitory efficiency of Gal-3 inhibitors through measurement of the fluorescent signal. Further studies show this model is simple, stable, and repeatable with a Z' factor between 0.7 and 0.85. In sum, we have successfully established an in vitro high-throughput screening model for Gal-3 inhibitors.

Metabolomic study on urine of chronic inflammation rats treated with Buyang Huanwu Decoction based on UPLC-Q-TOF-MS / 中国中药杂志

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

Undiagnosed Takayasu Arteritis in Pregnancy

@#Takayasu arteritis is a chronic inflammation involving large vessels and it often occurs in young women of childbearing age. We described a case of a 29- year- old lady with previous history of proliferative ischemic retinopathy was noted to have low upper limbs blood pressure and weak upper limb pulses postpartumly. An urgent CT angiogram of thorax revealed features suggestive of large vessel vasculitis with involvement of ascending arch, descending aorta and its main branches, corresponding to type II TA . She was diagnosed to have Takayasu arteritis post delivery, and she underwent a successful pregnancy without intrapartum and postpartum complications. High index of suspicion must be given for pregnant patient who have persistent low blood pressure and weak pulse for early detection to avoid severe complications.

Wendantang Treats Inflammation in Obesity （Syndrome of Phlegm-dampness） by Regulating PI3K/Akt/mTOR Pathway-mediated Adipocyte Autophagy / 中国实验方剂学杂志

ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines， autophagy markers， and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the adipocytes of the rat model of obesity （syndrome of phlegm-dampness） and to explore the material basis of inflammation in obesity （syndrome of phlegm-dampness） and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups： 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity （syndrome of phlegm-dampness） for 8 weeks. After successful modeling， 48 obese rats were selected according to their body mass and randomized into a model control group， an orlistat （ORLI， 32.40 mg·kg-1） group， a rapamycin （RAPA， 2 mg·kg-1） group， and low-， medium-， and high-dose （4.45， 8.90， 17.80 g·kg-1， respectively） Wendantang groups， with 8 rats in each group. In addition， 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass， Lee's index， body fat ratio， and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 （ULK1）， Beclin1， human autophagy-related protein 5 （Atg5）， p62， and microtubule-associated protein 1 light chain 3 （LC3） Ⅰ/Ⅱ （markers of autophagy in adipocytes） was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， IL-4， IL-10， IL-13， and transforming growth factor （TGF）-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K， phosphatidylinositol triphosphate （PIP3）， Akt， mTORC1， ULK1， TSC1， and TSC2 in adipocytes. ResultCompared with the blank group， the modeling group showed increased body mass and Lee's index （P<0.01）， the obesity rate >20%， and phlegm-dampness syndrome manifestations such as physical obesity， decreased mobility， decreased appetite， lusterless and tight fur， loose stools， decreased responsiveness to the outside world， and decreased water intake. Compared with the normal control group， the model control group showed increased body mass， Lee's index， body fat ratio， adipocyte autophagy marker expression， pro- and anti-inflammatory cytokine levels （P<0.05， P<0.01）， down-regulated protein levels of classⅠ-PI3K， PIP3， Akt， mTORC1， TSC1， and TSC2 （P<0.01）， and up-regulated protein level of ULK1 （P<0.01）. The intervention groups showed lower body mass， body fat ratio， adipocyte autophagy marker protein expression， and protein levels of TNF-α， IL-6， IL-1β， MCP-1， IL-4， and IL-13 than the model control group （P<0.05， P<0.01）. Moreover， the RAPA and Wendantang （medium and high dose） groups showed lowered levels of IL-10 and TGF-β （P<0.01）， and the ORLI group showed down-regulated expression of TGF-β （P<0.01）. The expression of key molecules of the signaling pathway was up-regulated （P<0.05， P<0.01） while that of ULK1 was down-regulated （P<0.01） in all the intervention groups. Compared with the RAPA group， the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes （P<0.01）. In addition， the low-dose Wendantang group showed elevated levels of inflammatory cytokines （except TNF-α） （P<0.05， P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.05， P<0.01）. The levels of inflammatory cytokines （except IL-16， MCP-1， and IL-10） were elevated in the medium-dose Wendantang group （P<0.05， P<0.01）. The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups （P<0.05， P<0.01）. Compared with the ORLI group， low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes （P<0.01）， and the low-dose group showed elevated levels of inflammatory cytokines （IL-6， IL-4， and TGF-β） （P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.01）. The medium-dose Wendantang group showed up-regulated expression of IL-4 （P<0.01） and down-regulated expression of key molecules except PI3K of the signaling pathway （P<0.05， P<0.01）. The high-dose Wendantang group showed increased body mass， up-regulated expression levels of autophagy markers （ULK1， LC3 Ⅰ/Ⅱ） （P<0.05， P<0.01）， down-regulated expression of PIP3， mTORC1， and TSC1 （P<0.05， P<0.01）， and lowered levels of Beclin1， Atg5， TNF-α， and IL-13 （P<0.05， P<0.01）. ConclusionThe inflammation in obesity （syndrome of phlegm-dampness） is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.

Effect of cangfudaotan decoction on TLR4/NF-κB p65 signaling pathway in obese PCOS-IR rats / 中国药理学通报

Aim To explore the regulatory effect of Cangfudaotan Decoction on the ovarian Toll receptor 4 (TLR4)/nuclear transcription factor kBp65 (NF-κB p65) signaling pathway in obese PCOS-IR rats. Methods Forty-eight female rats were randomly divided into normal group (n = 8) and model group (n = 40). The obese PCOS-IR rats were established by letrozole (1 mg · kg

Role of C5a/C5aR1 pathway in imiquimod-induced chronic psoriasis skin inflammation and the underlying mechanism / 中华微生物学和免疫学杂志

Objective:To establish a mouse model of imiquimod (IMQ)-induced chronic psoriasis skin inflammation and to investigate the role of C5a/C5aR1 pathway in this process and the underlying mechanism.Methods:BALB/c mice were treated with IMQ cream or Vasline cream (control group) every other day for eight times to mimic the chronic skin inflammation. Psoriatic skin inflammation and pathological changes in the wild-type (C5aR1 + /+ ) mice and the mice with C5aR1 gene deletion (C5aR1 -/-) were monitored and analyzed. Epidermal proliferation (Ki67), keratin 6/14 expression and neutrophil infiltration in the skin lesions were observed with immunohistochemical (IHC) staining. qRCR was used to detect the expression of keratin 6/14 and related inflammatory cytokines. Flow cytometry was performed to measure the percentages of leukocytes, CD3 + T cells and IL-17A + γδTCR + T cells in local skin samples as well as IL-17A responses in draining lymph nodes. Results:IMQ treatment induced typical psoriatic skin inflammation, including scaling, erythema and thickness. Dysregulated epidermal proliferation, acanthosis, micro-abscesses, inflammatory cell infiltration and abnormal hyperplasia of dermal capillaries were observed after HE staining. Compared with the C5aR1 + /+ mice, the C5aR1 -/- mice showed significantly attenuated chronic skin inflammation, evidenced by decreased epidermal proliferation, down-regulated keratin 6/14 expression and alleviated neutrophil infiltration. Results of qPCR also indicated decreased expression of keratin 6/14, inflammatory cytokines (IFN-γ, MIP-1α, IL-1β and TNF-α) and IL-17-related cytokines (IL-6, IL-17A and IL-23) in skin samples of C5aR1 -/- mice. Moreover, the infiltration of leukocytes (CD45), CD3 + T cells and IL-17A + γδTCR + T cells in skin lesions as well as the percentages of IL-17A + , IL-17A + CD3 + T and IL-17A + γδTCR + T cells in draining lymph nodes were also decreased in C5aR1 -/- mice. Conclusions:This study suggested that IMQ treatment could induce chronic psoriasis skin inflammation in mice. C5a/C5aR1 signaling pathway mediates IMQ induced chronic skin inflammation via activating IL-17 producing cells. Targeting C5a/C5aR pathway would be a new strategy for the management of psoriasis.

Establishment of a mouse model of chronic systemic inflammation with high circulating IL-6 / 中华微生物学和免疫学杂志

Objective:To establish an animal model of chronic systemic inflammation with long-term high expression of circulating IL-6 by introducing exogenous IL-6 gene transfer vector.Methods:Recombinant murine IL-6-encoding adeno-associated virus (AAV-IL-6) was constructed. Twenty-one 24-week-old male C57BL/6J mice were randomly divided into three groups with seven in each group: AAV-IL-6 group, vector control (AAV-ctrl) group and blank control group. At 0, 8 and 16 weeks of intervention, the mice in the three groups were injected with AAV-IL-6 (100 μl 0.5×10 10 vp/ml), unloaded AAV (100 μl 0.5×10 10 vp/ml) and the same volume of saline in the tail vein, respectively. IL-6 levels in mouse serum were measured by ELISA. The general condition of mice was observed and blood routine tests were performed. Changes in blood biochemical parameters and C-reactive protein (CRP) levels were detected. At the end of 24-week intervention, the mice were sacrificed and the myocardium, liver, spleen, quadriceps femoris, knee joint and middle femur were taken for HE staining. Results:At 4, 8, 16 and 24 weeks after intervention, serum IL-6 levels were (75.41-169.28) pg/ml in the AAV-IL-6 group, while in the two control groups, the levels were below the lower limit of detection (7.8 pg/ml). At 24 weeks after intervention, the body weight of mice in the AAV-IL-6 group was significantly lower than that of mice in the two control groups; the neutrophil counts and CRP level in the AAV-IL-6 group were higher than those in the two control groups, while the levels of albumin, creatinine, triglyceride and cholesterol were lower than those in the two control groups. There were no differences in the aforementioned parameters between the two control groups. Compared with the blank control group, both AAV-IL-6 and AAV-ctrl groups showed increased lymphocyte counts. All mice had normal liver and kidney functions at the end of intervention. Histopathological findings indicated that the mice in the AAV-IL-6 group had focal infiltration of lymphocytes in the central venous area of the liver and around the myocardial and the skeletal muscle fibers, diffuse infiltration of multinucleated giant cells in the spleen, atrophic skeletal muscle, disorganized growth plate, reduced chondrocyte hypertrophic zone, thinner bone cortex and trabecular, and reduced osteoid. There were no histopathological changes in mice of the two control groups.Conclusions:Repeated tail vein injection of AAV-IL-6 could achieve long-term high expression of circulating IL-6 in mice, which manifested the phenotype of chronic systemic inflammation in preliminary detection and provided a safe, effective and simply accessible animal model for related studies.

Effects of Xiangqin Jiere Granules on lipid metabolism and chronic inflammation in different obesity model mice / 中国中药杂志

This paper aims to study the effect of Xiangqin Jiere Granules(XQ) on lipid metabolism and chronic inflammation in different obesity model mice. The monosodium glutamate(MSG) obese mouse model was established by subcutaneous injection of MSG in newborn mice, and the high fat diet(HFD) obese mouse model was established by feeding adult mice with HFD. The normal mice were assigned into the control group; the MSG obese mice were assigned into MSG model group, XQ4.5 group(Xiangqin Jiere Granu-les, 4.5 g·kg~(-1)), XQ22.5 group(Xiangqin Jiere Granules, 22.5 g·kg~(-1)); the HFD obese mice were assigned into HFD model group, XQ4.5 group, and XQ22.5 group. The mice were intragastrically administrated with saline or XQ for 5 weeks. After that, the body weight, visceral fat mass, liver and thymus weight, and the organ indexes in each group were measured. The levels of triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-c) in serum and liver tissue were detected by the kits. The mRNA expression levels of acetyl CoA carboxylase 1(ACC1), fatty acid synthetase(FAS), diacylgycerol acyltransferase 1(DGAT1) and hepatic lipase(HTGL) involved in lipid metabolism in mouse liver tissue were detected by quantitative real-time PCR(qPCR). The protein levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in serum were detected by ELISA, and the mRNA levels of TNF-α and IL-6 in liver tissue were detected by qPCR. Compared with the control group, MSG and HFD mice showed increased body weight, abdominal circumference, Lee index and visceral fat mass as well as elevated levels of TG, TC, and LDL-c in serum. The model mice had up-regulated gene levels of ACC1, FAS and DGAT1 while down-regulated gene level of HTGL in the liver. Furthermore, the mRNA and protein levels of IL-6 increased in the model mice. Compared with the model mice, XQ treatment decreased the body weight, abdominal circumference, Lee index, and visceral fat mass, lowered the levels of TG, TC, and LDL-c in se-rum, down-regulated the gene levels of ACC1, FAS, and DGAT1 in liver tissue, up-regulated the gene level of HTGL, and down-regulated the mRNA and protein levels of IL-6. To sum up, XQ has good therapeutic effect on different obesity model mice. It can improve lipid metabolism and reduce fat accumulation in obese mice by regulating the enzymes involved in lipid metabolism, and alleviate obesity-related chronic low-grade inflammation.

Shenling Baizhu Powder alleviates chronic inflammation to prevent type 2 diabetes of ZDF rats via intestinal flora / 中国中药杂志

This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1β(IL-1β) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.

Progress on Correlation Between Type 2 Diabetes Mellitus and Malignant Tumors / 肿瘤防治研究

Type 2 diabetes mellitus and malignant tumors are two kinds of chronic diseases with tremendous impact on human health. Numerous epidemiological and clinical studies have shown that type 2 diabetes mellitus increases the risk of liver, pancreatic, endometrial, gallbladder, colorectal and breast cancers. Hyperglycemia can promote cancer cell proliferation, migration, invasion and immune escape through a variety of direct and indirect mechanisms. Insulin resistance and hyperinsulinemia can activate multiple signal transduction pathways through insulin/IGF-I signaling axis and promote tumorigenesis. Sustained chronic inflammatory responses can promote the development of cancer through DNA damage and pro-inflammatory factors. Gut microbiome dysbiosis is closely related to the occurrence of several gastrointestinal tumors. This paper reviews the progress on the correlation between type 2 diabetes mellitus and the progression of malignant tumors and the possible mechanisms.

Composition and histopathological features of prostatic calculi in patients with benign prostatic hyperplasia / 中华男科学杂志

Objective@#To analyze the composition of prostatic calculus in patients with BPH and explore its pathogenic factors and histopathological characteristics.@*METHODS@#Strictly following the inclusion and exclusion criteria, we included in this retrospective study 580 cases of bipolar transurethral plasma kinetic prostatectomy (TUPKP) performed in our hospital from May 2015 to May 2019, analyzed the histopathological and calculus-composition features of the patients with BPH complicated by prostatic calculi (the BPH+PC group) and the histopathological data of those with BPH only (the BPH group). We compared the related factors between the two groups of patients and performed uni- and multivariate logistic regression analyses of the data on those in the BPH+PC group.@*RESULTS@#The incidence rate of chronic inflammation was significantly higher in the BPH+PC than in the BPH group (83.1% vs 61.1%, P 0.05). Logistic regression analyses showed that prostatic calculus was significantly correlated with chronic inflammation of the prostate, the patient's age and IPSS (P 0.05).@*CONCLUSIONS@#Prostatic calculus has a high incidence in BPH patients and varies widely in composition, chiefly consisting of calcium oxalate and carbonate apatite. The major factors contributing to prostatic calculi include chronic inflammation of the prostate (primarily the severe type), age and BPH. Prostate calculi may aggravate lower urinary tract symptoms, especially urinary storage symptoms, in patients with BPH, but not significantly affect the PSA level.？.

Metabolic syndrome and skin diseases / 中华皮肤科杂志

Metabolic syndrome (MS) is a set of clinical symptoms characterized by multiple concurrent metabolic disorders, and is an important risk factor for type 2 diabetes and cardiovascular diseases in individuals. Its pathogenesis is still unclear, and may be associated with insulin resistance, chronic inflammatory reactions and oxidative stress. Studies have shown that MS is closely related to papulosquamous skin diseases, skin adnexal diseases, dermatitis and eczematous skin diseases, pigmentary skin disorders and so on. This review summarizes the relationship between MS and related skin diseases.

Efficacy of Modified Huanglian Wendantang and Shaofu Zhuyutang Against Ovulation Disorder in Combined Phlegm and Stasis-Induced Polycystic Ovary Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Huanglian Wendantang and Shaofu Zhuyutang in the treatment of ovulation disorder in patients with polycystic ovary syndrome （PCOS） due to the combined phlegm and stasis-induced and its influence on chronic inflammation. Method:According to the random number table， 100 patients were divided into a control group （50 cases） and an observation group （50 cases）. Apart from lifestyle intervention and oral administration of clomiphene citrate （CC） capsules to induce ovulation， patients in the control group further received Guizhi Fulingwan， 6 g/time， 2 times/day， while those in the observation group were treated with the modified Huanglian Wendantang and Shaofu Zhuyutang， 1 dose/day， for six menstrual cycles. The ovulation， endometrial thickness， proportion of type A endometrium， as well as the pulsatility index （PI） and resistance index （RI） of uterine artery were monitored before and after treatment. The fasting blood glucose （FBG）， fasting insulin （FINS）， luteinizing hormone （LH）， follicle stimulating hormone （FSH）， serum testosterone （T）， estradiol （E₂）， dehydroepiandrosterone sulfate （DHEAS）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， high-sensitivity C-reactive protein （hs-CRP）， adiponectin （APN）， and interleukin-6 （IL-6） levels before and after treatment were detected， followed by the calculation of homeostasis model assessment-insulin resistance （HOMA-IR） value and the evaluation of ovarian volume and combined phlegm and stasis-induced syndrome score. Result:The overall response rate of the observation group was （44/47） 93.62%， which was higher than （36/46） 78.26% of the control group （<italic>χ</italic>²=4.802， <italic>P</italic><0.05）. The ovulation rate in the observation group was （199/264） 75.38%， higher than （173/272） 63.60% in the control group （<italic>χ</italic>²=8.714， <italic>P</italic><0.01）. The clinical pregnancy rate of the observation group was （11/47） 23.40%， higher than （5/46） 10.87% of the control group， but the difference was not statistically significant （<italic>χ</italic>²=2.564， <italic>P</italic>>0.05）. Compared with the control group， the observation group exhibited reduced PI， RI， LH， T， DHEAS， FINS， FPG， HOMA-IR， TNF-<italic>α</italic>， hs-CRP， and IL-6 （<italic>P</italic><0.01）， but elevated E₂， FSH， and APN （<italic>P</italic><0.01）. Besides， the bilateral ovarian volume and combined phlegm and stasis-induced syndrome score of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， while the endometrial thickness and proportion of type A endometrium were higher （<italic>P</italic><0.01）. Conclusion:On the basis of CC treatment， the modified Huanglian Wendantang and Shaofu Zhuyutang alleviates the ovulation disorder in PCOS patients of combined phlegm and stasis-induced syndrome and regulates IR and chronic inflammation， thus creating a favorable condition for clinical pregnancy， which is worthy of further research.

Indicadores de valor pronóstico de amputación en pacientes hospitalizados con pie diabético / Indicators of amputation´s prognostic value in hospitalized patients with diabetic foot

Introducción: La diabetes mellitus es la causa más importante de amputaciones no traumáticas en el mundo. El pronóstico de riesgo de amputación resulta vital para el tratamiento óptimo de los pacientes hospitalizados con pie diabético. Objetivo: Caracterizar las variables con valor pronóstico de amputación en pacientes hospitalizados con diagnóstico de pie diabético. Método: Se realizó un estudio analítico longitudinal prospectivo en el período desde diciembre de 2015 hasta diciembre de 2017, con una muestra constituida por 77 pacientes. Las variables recogidas fueron edad, sexo, resultados hemoquímicos al ingreso, co-morbilidad, control glucémico y amputaciones realizadas, estos dos últimos durante la estadía hospitalaria. Se hizo inclusión de las variables con asociación significativa en un análisis univariado (p < 0,05) en un modelo de regresión logística múltiple para evaluar su asociación independiente. Se determinaron los valores predictivos positivos, negativos, y el grado de sensibilidad y especificidad. Resultados: Los indicadores pronósticos resultantes del análisis de las variables fueron el índice leuco-hematocrito (p = 0,045), el nivel de albúmina en sangre (p = 0,004), la glicemia a mitad del ingreso (p = 0,045) y la glicemia al ingreso (p = 0,039). El índice leuco-hematocrito, menor de 6 al ingreso, se relacionó con una especificidad de 92 por ciento; la albúmina, menor de 29,9 g/L, presentó un valor predictivo positivo de 71 por ciento; la glicemia al ingreso, mayor de 21,5 mmol/L, mostró una sensibilidad de 75 por ciento; y la glicemia a mitad del ingreso, mayor de 12,9 mmol/L, manifestó una sensibilidad de 71 por ciento. Conclusiones: La evolución a la amputación de los pacientes ingresados por pie diabético se relaciona con el estado inflamatorio crónico, el estado nutricional y el control glucémico(AU)

Introduction: Diabetes mellitus is the most important cause of non-traumatic amputations in the world. The prognosis of amputation risk is vital for the optimal treatment of patients hospitalized with diabetic foot disease. Objective: Characterize variables with amputation´s prognostic value in hospitalized patients diagnosed with diabetic foot disease. Method: A prospective longitudinal analytical study was conducted in the period from December 2015 to December 2017, with a sample consisting of 77 patients. The variables collected were age, sex, hemochemical results upon admission, co-morbidity, glycaemic control and amputations performed, the latter two during the hospital stay. Variables with significant association were included in a one-variety analysis (p < 0.05) in a multiple logistic regression model to evaluate their independent association. Positive, negative predictive values, and the degree of sensitivity and specificity were determined. Results: The prognosis indicators resulting from the analysis of the variables were the leuko-hematocrit index (p = 0.045), the level of albumin in blood (p = 0.004), the glycaemia at the mid-time of the stay (p = 0.045) and the glycaemia at the admission time (p = 0.039). The leuko-hematocrit index, in less than 6 patients at admission time, was related to a specificity of 92 percent; albumin, in less than 29.9 g/L, had a positive predictive value of 71 percent; glycaemia at admission time, higher than 21.5 mmol/L, showed a sensitivity of 75 percent;and glycaemia at mid-time of the stay, higher than 12.9 mmol/L, showed a sensitivity of 71 percent. Conclusions: The evolution to amputation of patients admitted due to diabetic foot is related to chronic inflammatory state, nutritional state and glycaemic control(AU)

Is the C-reactive protein/albumin ratio a prognostic and predictive factor in sudden hearing loss? / A relação proteína C-reativa/albumina é um fator prognóstico e preditivo na surdez súbita?

Abstract Introduction: Sudden hearing loss is a significant otologic emergency. Previous studies have revealed a coexistence of sudden hearing loss with chronic inflammation. The predictive importance of C-reactive protein/albumin values as a prognostic factor has been shown in various inflammatory and tumoral conditions. Objectives: The aim of this study was to determine whether the C-reactive protein/albumin ratio in sudden hearing loss can be used for prognostic purposes and whether there is a relationship between the neutrophil/lymphocyte ratio and the C-reactive protein/albumin ratio. Methods: A retrospective examination was made of 40 patients diagnosed with idiopathic sudden hearing loss and a control group of 45 healthy subjects. The pure tone averages of all the patients were determined on first presentation and repeated at 3 months after the treatment. The patients were separated into 2 groups according to the response to treatment. The neutrophil/lynphocyte ratio and the C-reactive protein/albumin ratios were calculated from the laboratory tests. Results: The patients included 16 females and 24 males with a mean age of 44.1 ± 14.2 years and the control group was composed of 23 females and 22 males with a mean age of 42.2 ± 13.8 years. The mean C-reactive protein/albumin ratio was 0.95 ± 0.47 in the patient group and 0.74 ± 0.13 in the control group. The difference was statistically significant (p = 0.009). The mean C-reactive protein/albumin ratio was 0.79 ± 0.12 in the response to treatment group and 1.27 ± 0.72 in the non-response group, with no significant difference determined between the groups (p = 0.418). The mean neutrophil/lymphocyte ratio was 3.52 ± 3.00 in the response to treatment group and 4.90 ± 4.60 in the non-response group, with no statistically significant difference determined between the groups (p = 0.261). Conclusion: C-reactive/albumin ratio was significantly higher in patients with sudden hearing loss than in the control group. Although C-reactive protein/albumin ratio was found to be lower in sudden hearing loss patients who responded to treatment compared to those who did not, the difference between two groups was not statistically significant.

Resumo Introdução: A perda auditiva neurossensorial súbita ou surdez súbita é uma emergência otológica significativa. Estudos anteriores revelaram uma coexistência dessa condição com inflamação crônica. A importância preditiva dos valores da relação proteína C-reativa/albumina como fator prognóstico tem sido demonstrada em várias condições inflamatórias e tumorais. Objetivos: O objetivo deste estudo foi determinar se a relação proteína C-reativa/albumina na perda auditiva neurossensorial súbita pode ser usada para fins prognósticos e se existe uma associação entre as relações neutrófilo/linfócito e proteína C-reativa/albumina. Método: Foram avaliados retrospectivamente 40 pacientes com diagnóstico de perda auditiva neurossensorial súbita idiopática e um grupo controle de 45 indivíduos saudáveis. As médias de tons puros de todos os pacientes foram determinadas na primeira consulta e repetidas 3 meses após o tratamento. Os pacientes foram separados em 2 grupos de acordo com a resposta ao tratamento. As relações neutrófilo/linfócito e proteína C-reativa/albumina foram calculadas a partir de testes laboratoriais. Resultados: Os pacientes incluíam 16 mulheres e 24 homens, com média de 44,1 ± 14,2 anos, e o grupo controle por 23 mulheres e 22 homens, com média de 42,2 ± 13,8 anos. A média da relação proteína C-reativa/albumina foi de 0,95 ± 0,47 no grupo de pacientes e de 0,74 ± 0,13 no grupo controle e a diferença foi estatisticamente significante (p = 0,009). A média da relação proteína C-reativa/albumina foi de 0,79 ± 0,12 do grupo com resposta ao tratamento e de 1,27 ± 0,72 no grupo sem resposta, sem diferença significante entre os grupos (p = 0,418). A média da relação neutrófilo/linfócito foi de 3,52 ± 3,00 no grupo com resposta ao tratamento e de 4,90 ± 4,60 no grupo sem resposta, sem diferença estatisticamente significativa entre os grupos (p = 0,261). Conclusão: A relação proteína C-reativa/albumina foi significantemente maior nos pacientes com perda auditiva neurossensorial súbita do que no grupo controle. No entanto, embora a relação proteína C-reativa/albumina tenha sido menor nos pacientes com perda auditiva neurossensorial súbita que responderam ao tratamento em comparação a aqueles que não apresentaram resposta, a diferença entre os dois grupos não foi estatisticamente significante.

Advances in research on mechanisms of diabetic wound healing / 药学学报

Wound healing is a complex and highly regulated process to maintaining the skin barrier function. Wounds of diabetic patients are hard or even not healing. Non-healing diabetic foot ulcers can lead to lower-extremity amputations. Diabetic wound healing problem is the main complication that leads to high disability rate of diabetes and can threaten the lives in severe cases. The healing of skin wounds requires the synergy of multiple factors to restore the injured skin to its barrier function. The mechanisms that cause it difficult to heal diabetic wounds are complex, including oxidative stress, chronic inflammation, decreased neovascularization, peripheral neuropathy, and imbalance of extracellular matrix accumulation and remodeling. This review classifies mechanisms of diabetic wound healing and provides a reference for its further research.

Research progress on the relationship between Candida albicans and oral potentially malignant disorders / 口腔疾病防治

@#Oral potentially malignant disorders (OPMDs) refer to all epithelial lesions and conditions with an increased risk for malignant transformation, including oral leukoplakia, oral submucous fibrosis, oral lichen planus, erythroplakia, etc. Additionaly, oral infection of Candida albicans is considered to be closely related to the development of OPMDs. It was demonstrated in previous studies that the detection rate of Candida albicans was higher in the oral mucosa with OPMDs; in addition, Candida albicans showed high virulence by adhering to and destroying the epithelium. Moreover, Candida albicans was able to induce the immune response and cause chronic inflammation in the epithelium, producing carcinogenic products such as acetaldehyde. The factors mentioned above play a key role in the occurrence and development of OPMDs. Furthermore, the oral mucosa is highly susceptible to Candida albicans. The present review provides an introduction to the relationship between Candida albicans and OPMDs.

Role and mechanism of microRNAs in oral lichen planus / 口腔疾病防治

@#Oral lichen planus (OLP) is a chronic inflammatory disease of the mucosa, some of which will develop into oral squamous cell carcinoma (OSCC). However, the pathogenesis of OLP remains unknown, but autoimmunity has been suggested as a potential cause. MicroRNAs (miRNAs), which are small noncoding RNAs, have been reported to be involved in a series of physiological events as well as the progression of diseases. The evidence indicates that miRNAs may be highly related to both the initiation and malignant progression of OLP. MiR-146a, miR-26b, miR-155, miR-19a and miR-125a are able to trigger OLP by regulating autoimmunity, and miR-137, miR-125b, and miR-27b may accelerate the carcinogenesis of OLP. These miRNAs may be potential targets for prognosis and treatment. Subsequent studies are expected to focus on a more comprehensive exploration of the role of miRNAs in OLP (including specific action pathways and other OLP-related miRNAs), as well as the potential for miRNAs to predict the treatment outcome of OLP. This review provides an updated summary of the roles of miRNAs in OLP to provide new ideas and approaches to OLP research.

NLRP3 inflammasome in metabolic syndrome

Metabolic syndrome (MS) is a serious health problem worldwide; it is characterized by a group of metabolic disorders, including central obesity, insulin resistance/type 2 diabetes, hyperlipidemia with accelerated atherosclerosis, hypertension, non-alcoholic fatty liver disease, and elevated uric acid with increased risk of gout. The incidence of MS has increased considerably in recent decades and has attracted considerable attention. A number of clinical and translational laboratory studies have implicated the activation of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in the development of MS, therefore establishing a strong link between chronic inflammation and metabolic diseases. This paper aims to review new developments on NLRP3 inflammasome in MS for better understanding of chronic inflammation in metabolic diseases. We will also provide new insights into using NLRP3 inflammasome as an innovative therapeutic target.