Advances in drug therapy of meibomian gland dysfunction / 中华实验眼科杂志

Meibomian gland dysfunction (MGD) is a chronic, diffuse meibomian gland disorder, which has complex pathogenesis and high prevalence.It has become one of the common ocular surface diseases in clinics, and its treatment has been the clinical research focus and a challenge over the years.The traditional treatments consist of lifestyle improvement, physical therapy, medical treatments and surgery, in which drug plays an important role.According to the etiology and pathogenesis of MGD, the applied drugs can be classified into three categories.The first category is to improve the quality of tears and the stability of tear film, including artificial tear and ocular surface lubricants, secretagogues (promoting the secretion of lipids, aqueous solution and mucin), androgens, etc.The second category is to improve the ocular surface microenvironment, including local and systemic antibiotics, glucocorticoid eyedrops, non-steroidal anti-inflammatory drugs, immunosuppressants, anti-mites drugs, etc.The third category is nutritional supplements and neuroprotectants, including vitamin D3, omega-3 fatty acids, autologous serum and so on.This review focused on widely-used and current emerging treatment options, aiming to provide references for clinical treatments and further study on MGD.

Mechanism of Zhishi Xiebai Guizhi Decoction on myocardial infarction based on network pharmacology and experimental validation / 中国药理学通报

Aim To explore the effects of Zhishi Xiebai Guizhi Decoction (ZXGD) in the treatment of myocardial infarction (MI) using the network pharmacology method and verifying by in vivo experiments and to reveal the underlying mechanism. Methods The chemical components of ZXGD and related targets were retrieved from the TCMSP database. The targets of MI were searched from the GeneCards, OMIM and DisGeNET databases, with the keywords " myocardial infarction" and "MI", and removing duplicates. The intersection of ZXGD and MI targets were obtained, and a protein-protein interaction (PPI) network based on the intersection of active ingredients and disease targets was constructed. The DAVID database was used to conduct GO and KEGG pathway enrichment analysis on the intersection targets. Combined with STRING database and Cytoscape 3.7.2 software, the intersection targets were visualized as a " medicine-component-target-disease" network. The MI mouse model was established by ligation of the left anterior descending coronary artery of the heart. ZXGD was given once a day for 14 days. The cardioprotective effects of ZXGD were examined by ultrasound cardiogram and Western blot. Results The results of network pharmacology analysis showed that the pharmacological components of ZXGD such as quercetin, naringenin, β-sitosterol, and luteolin maybe work on the targets like TNF-α, IL-1β, IL-6, VEGFA, and IL-10. Animal experiments found that compared with the model group, ZXGD significantly increased the left ventricular cardiac function, outflow tract blood flow, and other ultrasound indexes of the mice (P < 0.05). Moreover, the expression levels of IL-1β, TNF-α and IL-6 in myocardial infarction tissue were significantly down-regulated by ZXGD (P < 0.05), while the expression level of IL-10 was significantly up-regulated (P < 0.05). Conclusion ZXGD protects against MI and improves heart function by regulating inflammatory factors including TNF-α, IL-1β, IL-6, and IL-10.

Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway / 中国中药杂志

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Effect of anterior capsule polishing on the visual quality after cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the effect of anterior capsule polishing on visual quality after phacoemulsification.METHODS: Prospective randomized control study. A total of 65 patients(73 eyes)with age-related cataract who underwent phacoemulsification combined with intraocular lens(IOL)implantation in the Emergency General Hospital between November 2021 and June 2022 were included. These patients were randomly assigned to two groups, with one group(anterior polishing group)underwent anterior and posterior capsule polishing(30 cases, 35 eyes), while the other(control group)receive routine posterior capsule polishing(35 cases, 38 eyes). Best corrected visual acuity was observed at 1wk, 1, 3 and 6mo after operation. Area of anterior capsule orifice was measured at 3 and 6mo after operation. Meanwhile, posterior capsular opacification(P score), IOL tilt and decentration were recorded by Pentacam Scheimpflug system. In addition, wavefront aberration, Strehl ratio(SR)of point spread function(PSF)and modulation transfer function(MTF)were evaluated by OPD-Scan Ⅲ.RESULTS: At 1wk, 1, 3 and 6mo after operation, best corrected visual acuity in anterior polishing group is significantly better than that of control group(P&#x003C;0.05). There were no significant differences in area of anterior capsule opening, P score, IOL decentration, SR of PSF and MTF between two groups at 3 and 6mo after operation(P&#x003E;0.05). At 3mo follow-up, no significant differences in IOL tilt and wavefront aberration were measured between two groups either(P&#x003E;0.05). However, IOL tilt [(1.65±0.60)° vs.(2.34±0.43)°, P&#x003C;0.001] and wavefront aberration(0.03±0.01μm vs. 0.06±0.03μm, P&#x003C;0.001)in anterior polishing group were significant lower compared to control group at 6mo after operation.CONCLUSION: 360° polishing of anterior and posterior capsule during phacoemulsification can improve best corrected visual quality, with reduced IOL tilt, lower wavefront aberration and better visual quality.

Effect of Rhizophagus intraradices on growth of Salvia miltiorrhiza / 中国中药杂志

The study aimed to explore the effects of inoculation of Rhizophagus intraradices on the biomass, effective component content, and endogenous hormone content of Salvia miltiorrhiza through pot experiments. The number of leaves, plant height, dry weight of aboveground and underground parts, branch number, root number, root length, root diameter, and other biomass were mea-sured by weighing and counting methods. The content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, tanshinone Ⅱ_A, cryptotanshinone, and other effective components was determined by ultra-high performance liquid chromatography. The content of ABA and GA_3 was determined by triple quadrupole mass spectrometry. The correlations between biomass and effective components and between effective components and plant hormones ABA and GA_3 were analyzed. The results showed that R. intraradices significan-tly increased the aboveground dry weight, leaf number, and root number of S. miltiorrhiza by 0.24-0.65 times, respectively. The content of salvianolic acid B and rosmarinic acid in the aboveground part and the content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, and tanshinone Ⅱ_A in the underground part were significantly increased by 0.44-1.78 times, respectively. R. intraradices infection significantly increased the GA_3/ABA values of aboveground and underground parts by 3.82 and 76.47 times, respectively. The correlation analysis showed that caffeic acid, the effective component of the aboveground part, was significantly positively correlated with plant height, tanshinone Ⅱ_A, the effective component of the underground part, was significantly positively correlated with biomass root number, cryptotanshinone, and dry weight, while rosmarinic acid was significantly negatively correlated with dry weight. There were significant positive correlations between cryptotanshinone and ABA, tanshinone Ⅱ_A and ABA and GA_3, and caffeic acid and GA_3. In conclusion, R. intraradices can promote the accumulation of biomass and secondary metabolites of S. miltiorrhiza and regulate the balance between plant hormones ABA and GA_3, thereby promoting the growth of S. miltiorrhiza.

Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urine arsenic and urine creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urine arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urine arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/L and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction<0.05). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18-79 years.

Association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China / 中华预防医学杂志

Objective: To investigate the association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B12 and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B12, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B12 level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B12 level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B12 level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q1, Q3) level of plasma vitamin B12 was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B12 level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B12 (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B12 with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.

Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

Toxicity comparison of psoralen in 2D /3D hepatocyte models and its effect on mitochondrial fusion and fission / 中国药理学通报

Aim To evaluate and compare the toxicity of psoralen on two-dimensional(2D)and three-dimensional(3D)cultured human hepatocyte HepG2 models. Methods The 3D cell model of HepG2 cells was constructed by low adsorption U-shaped bottom porous plate method. After treated with psoralen for 24 hours, the cell viabilities of 2D and 3D HepG2 cells were detected by CCK-8 assay, LDH leakage was detected by kit, and the mitochondrial membrane potential was detected by TMRM staining. The effect of psoralen on the mRNA of mitochondrial fusion-fission proteins DRP1, Mfn-2 and OPA1 was detected by Q-PCR. Results 3D model maintained a high level of albumin and urea secretion for a long time. And the expression levels of CYP1A2, CYP2E1, CYP3A4 and UGT1A1 in 3D model were higher than those in 2D model. In 3D model lower concentrations of psoralen showed a significant decrease in cell viability, a significant increase in LDH leakage, and a decrease in mitochondrial membrane potential. Q-PCR results showed that psoralen induced a marked increase in the expression of mitochondrial fission protein DRP1, while a significant decrease in mitochondrial fusion protein OPA1. Conclusions A 3D HepG2 cell model is successfully constructed and applied to the evaluation of psoralen hepatotoxicity; the 3D cell culture model is more sensitive to psoralen toxicity, and mitochondria may play a key role in psoralen-induced cell damage.

Berberine affects activity of HSV-1 virus infected HEp-2 cells and its molecular mechanism / 中国药理学通报

Aim To discuss the effect of berberine ( BE) on the activity of HSV-1 virus infected HEp-2 cells and its related molecular mechanisms.Methods Hie infected cell model was constructed and divided into control group, infection group, low concentration group ( 5 (xmol • L 1 -BE) , medium concentration group ( 10 (xmol • L '-BE) and high concentration group ( 15 (xmol • L '-BE) ) , and then incubated for 24 hours.qRT-PCR was used to determine HSV-1 infection-related genes ( gD, ICP-4, ICP-8, ICP-27 ) and mRNA expression levels of LncBNA NRAV, miR- 299-3p, RAB5C.CCK-8 method and flow cytometry were applied to detect cell viability and apoptotic rate.The expression levels of PI3K/AKT signaling pathway and JNK/p38 MAPK signaling pathway related protein were analysed by WB.Results It was found that BE j j reduced the mRNA expression of gD, ICP-4, ICP-8, anrl ICP-27, improved cell viability, and inhibited eell apoptosis.BE promoted the expression of miR-299-3p by inhibiting LncRNA NRAV and RAB5C.BE inhibited the protein expression levels of PBK/AKT signaling pathway and JNK/p38 MAPK signaling pathway proteins PI3K, AKT, JNK, and P38.Conclusions The mechanism that BE enhances the activity of HEp-2 cells after HSV-1 infection and suppresses its apoptosis may be related to LncRNA NRAV and RAB5C targeting competitive binding to miH-299-3p, inhibiting the activation of PBK/AKT signaling pathway and JNK/ p38 MAPK signaling pathway.

Effect of Wenyang Huazhuo Tongluo formula on Sema3A/Nrpl signaling pathway in systemic sclerosis mouse model / 中国药理学通报

Aim To study the effeet of Wenyang Hua- Nrpl signaling pathway in systemic sclerosis ( SSc ) zhuo Tongluo formula ( WYHZTLF) on the Sema3A/ mouse model, and to explore its mechanism in the treatment of SSe.Methods The systemic sclerosis mouse model was constructed and divided into control group, model group, WYHZTLF low (21 g • kg 1 ) , medium (42 g • kg 1 ) , high (84 g • kg 1 ) dose group and the Sema3A inhibitor epigallocatechol gallate (EGCG) group.All groups were given intragastric administration for four weeks, and the control and model groups were treated with saline.Histopathology and dermal thickness were detected by HE, VEGFA pro-tein expression levels were detected by immunohisto- chemistry; the protein expression levels of Sema3A, Nrpl and VEGFA were determined by Western blot; Sema3A expression levels in mouse serum were detec-terl by ELISA.Results Comparer] with model group, WYHZTLF significantly alleviated the skin lesions in systemic sclerosis mouse model, significantly inhibited the dermal thickness, inhibited the protein expression levels of VEGFA, Sema3A and Nrpl , and reduced the expression levels of serum Sema3A.Conclusion WYHZTLF can improve the vascular injury of SSc, and its mechanism may be related to the inhibition of VEGFA and Sema3A/Nrpl signaling pathway.

Mechanism Analysis of Strengthening Anti-cerebral Ischemia Injury of Chuanxiong Rhizoma Processed with Wine Based on UHPLC-Q-Orbitrap HRMS and Integrated Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the differential components in water extract of Chuanxiong Rhizoma before and after processing with wine， and to explore the molecular mechanism of Chuanxiong Rhizoma processed with wine in enhancing anti-cerebral ischemia injury. MethodUltra high performance liquid chromatography tandem quadrupole orbitrap high resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to qualitatively analyze the main chemical components in water extract of Chuanxiong Rhizoma based on the spectral information of compound， comparison of reference substance and references. The chemical pattern recognition method was used to screen the differential components of Chuanxiong Rhizoma before and after processing. Based on these differential components， the potential targets of differential components were predicted by online databases， and the related targets of cerebral ischemia were searched. Cytoscape 3.6.0 was used to establish the network diagram of differential components-action targets-diseases of Chuanxiong Rhizoma processed with wine. The protein-protein interaction （PPI） network of intersection targets was constructed by STRING 11.5. The potential targets of differential components against cerebral ischemia were analyzed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis through DAVID 6.8. At the same time， the chemical compounds with high relative content and increased peak area after wine processing were docked with their corresponding targets to verify the mechanism of enhanced effect after wine processing. ResultA total of 71 chemical components were identified from Chuanxiong Rhizoma， 34 differential components and 603 potential targets were screened out. At the same time， a total of 769 disease targets and 60 intersection targets were obtained. Seven key targets were identified through PPI network analysis， including JUN， signal transducer and activator of transcription 3 （STAT3）， mitogen-activated protein kinase 3 （MAPK3）， interleukin-1β （IL-1β）， vascular endothelial growth factor A （VEGFA）， Caspase-3 （CASP3） and mtrix metalloproteinase 9 （MMP9）. Tumor necrosis factor （TNF） signaling pathway was the main differential signaling pathway. The results of molecular docking showed that differential components （senkyunolide K， senkyunolide F， 3-n-butylphthalide， Z，Z′-6，8′，7，3′-diligustilide， ferulic acid and Z-ligustilide） and corresponding targets had good binding activities. ConclusionThe synergistic mechanism of Chuanxiong Rhizoma processed with wine may be related to the enhanced inhibitory effect of inflammatory reaction.

Study on the mechanism of Wenyang huazhuo tongluo formula contained serum inhibiting the proliferation of Th17 cells in scleroderma patients / 中国药房

OBJECTIVE To study the effects of Wenyang huazhuo tongluo formula conta ined serum on the expression and methylation of retinoic acid related nuclear orphan receptor （RORγt），and to explore the mechanism of its regulation of Th 17 cell proliferation in the treatment of scleroderma. METHODS Wistar rats were given 15，30，60 g/（kg·d）Wenyang huazhuo tongluo formula intragastrically to prepare different doses of drug-contained serum ，and peripheral blood of scleroderma patients were collected to sort Th 17 cells. Using blank serum as blank control ，methyltransferase inhibitor decitabine （DCA）as positive control ， Th17 cells were treated with different concentrations of drug-contained serum ，and then the proliferation of Th 17 cells was detected by CCK- 8；mRNA expressions of RORγt and IL-17 were detected by qRT-PCR ，and the protein expression of RORγt was detected by Western blot assay ；the protein expression of IL- 17 in the cell supernatant was detected by ELISA ，and the methylation level of RORγt gene promoter was detected by methylation-specific PCR. The transcriptional activity of RORγt gene promoter was detected by dual-luciferase assay. RESULTS Compared with blank control ，Wenyang huazhuo tongluo formula contained serum and DCA could inhibit the proliferation of Th 17 cells（P＜0.05），reduced the mRNA and protein expressions of RORγt and IL-17，enhanced the methylation level of RORγt gene promoter and attenuated ， the transcription activity of RORγt gene promoter. Except for mRNA expression of Th 17 and the methylation level of RORγt gene promoter in drug-contained serum low-dose group ，there were statistical significance in above indexes of other groups（P＜0.05）. CONCLUSIONS Wenyang huazhuo tongluo formula can promote the methylation lev el of RORγt gene，and inhibit the expression of RORγt and the secretion of IL-17，so as to inhibit the proliferation of Th 17 cells.

Association of blood lead and blood selenium with serum high-sensitivity C-reactive protein among Chinese adults aged 19 to 79 years / 中华流行病学杂志

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Histological Changes of Cervical Disc Tissue in Patients with Degenerative Ossification

Objective@#: To explore the histological feature of the cervical disc degeneration in patients with degenerative ossification (DO) and its potential mechanisms. @*Methods@#: A total of 96 surgical segments, from cervical disc degenerative disease patients with surgical treatment, were divided into ossification group (group O, n=46) and non-ossification group (group NO, n=50) based on preoperative radiological exams. Samples of disc tissues and osteophytes were harvested during the decompression operation. The hematoxylin-eosin staining, Masson trichrome staining and Safranin O-fast green staining were used to compare the histological differences between the two groups. And the distribution and content of transforming growth factor (TGF)-β1, p-Smad2 and p-Smad3 between the two groups were compared by a semi-quantitative immunohistochemistry (IHC) method. @*Results@#: For all the disc tissues, the content of disc cells and collagen fibers decreased gradually from the outer annulus fibrosus (OAF) to the central nucleus pulposus (NP). Compared with group NO, the number of disc cells in group O increased significantly. But for proteoglycan in the inner annulus fibrosus (IAF) and NP, the content in group O decreased significantly. IHC analysis showed that TGF-β1, p-Smad2, and p-Smad3 were detected in all tissues. For group O, the content of TGF-β1 in the OAF and NP was significantly higher than that in group NO. For p-Smad2 in IAF and p-Smad3 in OAF, the content in group O were significantly higher than group NO. @*Conclusion@#: Histologically, cervical disc degeneration in patients with DO is more severe than that without DO. Local higher content of TGF-β1, p-Smad2, and p-Smad3 are involved in the disc degeneration with DO. Further studies with multi-approach analyses are needed to better understand the role of TGF-β/Smads signaling pathway in the disc degeneration with DO.

Construction of a high-throughput screening model for mitochondrial function of Aconiti Lateralis Radix Praeparata by machine learning algorithm and mechanism analysis / 中国中药杂志

A high-throughput screening machine learning model for mitochondrial function was constructed, and compounds of Aco-niti Lateralis Radix Praeparata were predicted. Deoxyaconitine with the highest score and benzoylmesaconine with the lowest score among the compounds screened by the model were selected for mitochondrial mechanism analysis. Mitochondrial function data were collected from PubChem and Tox21 databases. Random forest and gradient boosted decision tree algorithms were separately used for mo-deling, and ECFP4(extended connectivity fingerprint, up to four bonds) and Mordred descriptors were employed for training, respectively. Cross-validation test was carried out, and balanced accuracy(BA) and overall accuracy were determined to evaluate the performance of different combinations of models and obtain the optimal algorithm and hyperparameters for modeling. The data of Aconiti Lateralis Radix Praeparata compounds in TCMSP database were collected, and after prediction and screening by the constructed high-throughput screening machine learning model, deoxyaconitine and benzoylmesaconine were selected to measure mitochondrial membrane potential, reactive oxygen species(ROS) level and protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax) and peroxisome proliferator-activated receptor-γ-coactivator 1α(PGC-1α). The results showed that the model constructed using gradient boosted decision tree+Mordred algorithm performed better, with a cross-validation BA of 0.825 and a test set accuracy of 0.811. Deoxyaconitine and benzoylmesaconine changed the ROS level(P<0.001), mitochondrial membrane potential(P<0.001), and protein expression of Bcl-2(P<0.001, P<0.01) and Bax(P<0.001), and deoxyaconitine increased the expression of PGC-1α protein(P<0.01). The high-throughput screening model for mitochondrial function constructed by gradient boosted decision tree+Mordred algorithm was more accurate than that by random forest+ECFP4 algorithm, which could be used to build an algorithm model for subsequent research. Deoxyaconitine and benzoylmesaconine affected mitochondrial function. However, deoxyaconitine with higher score also affected mitochondrial biosynthesis by regulating PGC-1α protein.

PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis

Abstract Background: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result: When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.

Cardiovascular and renal burdens of metabolic associated fatty liver disease from serial US national surveys, 1999-2016 / 中华医学杂志(英文版)

BACKGROUND@#Non-communicable chronic diseases have become the leading causes of disease burden worldwide. The trends and burden of "metabolic associated fatty liver disease" (MAFLD) are unknown. We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged ≥20 years from the cross-sectional US National Health and Nutrition Examination Survey periods, 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2016. MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity, type 2 diabetes mellitus, or evidence of metabolic dysregulation.@*RESULTS@#The prevalence of MAFLD increased from 28.4% (95% confidence interval 26.3-30.6) in 1999 to 2002 to 35.8% (33.8-37.9) in 2011 to 2016. In 2011 to 2016, among adults with MAFLD, 49.0% (45.8-52.2) had hypertension, 57.8% (55.2-60.4) had dyslipidemia, 26.4% (23.9-28.9) had diabetes mellitus, 88.7% (87.0-80.1) had central obesity, and 18.5% (16.3-20.8) were current smokers. The 10-year cardiovascular risk ranged from 10.5% to 13.1%; 19.7% (17.6-21.9) had chronic kidney diseases (CKDs). Through the four periods, adults with MAFLD showed an increase in obesity; increase in treatment to lower blood pressure (BP), lipids, and hemoglobin A1c; and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus. Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs, myocardial infarction, or stroke. Generally, although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD, the prevalence of MAFLD was significantly higher than that of NAFLD.@*CONCLUSIONS@#From 1999 to 2016, cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD. The absolute cardiorenal burden may be greater for MAFLD than for NAFLD. These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.

Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via a Network Pharmacology Approach / 中国结合医学杂志

OBJECTIVE@#To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment.@*METHODS@#A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets.@*RESULTS@#Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway.@*CONCLUSIONS@#The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

Influence of Yuanzhisan Containing Ginseng Radix et Rhizoma or Codonopsis Radix on Memory Disorder / 中国实验方剂学杂志

Objective:To explore the effects of Yuanzhisan （YZS） containing Ginseng Radix et Rhizoma （YZSR） or Codonopsis Radix （YZSD） on memory disorder based on network and experimental pharmacology. Method:The active components and targets of YZS were retrieved from the component database and literature， and the targets of memory disorder from the disease databases. The intersection targets revealed by Veen diagram were subjected to pathway analysis. The common active components of YZSR and YZSD were molecularly docked onto the core targets. Scopolamine hydrobromide was used to establish the memory disorder model， which was employed in the behavioral experiments for evaluating the effect of YZSR and YZSD on memory disorder. Result:There existed 33 active components for Ginseng Radix et Rhizoma and 31 for Codonopsis Radix， with four common active components and 380 common targets. YZSR contained 85 active components and 790 drug targets， and YZSD 81 active components and 781 drug targets. The mapping of 425 memory disorder targets with those of YZSD and YZSD yielded 133 and 130 intersection targets， respectively. The metabolic pathways involved calcium ion signaling pathway， hypoxia-inducible factor-1 （HIF-1） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， etc. As revealed by molecular docking， the binding energy of common active components to the targets was negative， and the binding effect of frutinone A was the best. Behavioral experiment results showed that both YZSR and YZSD alleviated the memory disorder. In the step-down test， the number of errors in the YZSD group was significant lower than that in the model group （<italic>P</italic><0.01）. In Morris water maze test， the movement distance of the YZSD group was remarkably shortened in comparison with that of the model group （<italic>P</italic><0.05）. In the open field test， the movement distances of both the YZSR and YZSD group were shortened in contrast to that in the normal group （<italic>P</italic><0.05）. Conclusion:YZS had a certain effect on memory disorder. There are similarities and differences between YZSR and YZSD in the treatment of memory disorder.