QKL injection ameliorates Alzheimer's disease-like pathology by regulating expression of RAGE.

The onset of Alzheimer's disease is related to neuron damage caused by massive deposition of Aß in the brain. Recent studies suggest that excessive Aß in the brain mainly comes from peripheral blood, and BBB is the key to regulate Aß in and out of the brain. In this study, we explored the pathogenesis of AD from the perspective of Aß transport through the BBB and the effect of QKL injection in AD mice. The results showed that QKL could improve the cognitive dysfunction of AD mice, decrease the level of Aß and Aß transporter-RAGE, which was supported by the results of network pharmacology, molecular docking and molecular dynamics simulation. In conclusion, RAGE is a potential target for QKL's therapeutic effect on AD.

ARGONAUTE10 controls cell fate specification and formative cell divisions in the Arabidopsis root.

A key question in plant biology is how oriented cell divisions are integrated with patterning mechanisms to generate organs with adequate cell type allocation. In the root vasculature, a gradient of miRNA165/6 controls the abundance of HD-ZIP III transcription factors, which in turn control cell fate and spatially restrict vascular cell proliferation to specific cells. Here, we show that vascular development requires the presence of ARGONAUTE10, which is thought to sequester miRNA165/6 and protect HD-ZIP III transcripts from degradation. Our results suggest that the miR165/6-AGO10-HDZIP III module acts by buffering cytokinin responses and restricting xylem differentiation. Mutants of AGO10 show faster growth rates and strongly enhanced survival under severe drought conditions. However, this superior performance is offset by markedly increased variation and phenotypic plasticity in sub-optimal carbon supply conditions. Thus, AGO10 is required for the control of formative cell division and coordination of robust cell fate specification of the vasculature, while altering its expression provides a means to adjust phenotypic plasticity.

Dissecting the genome sequence of a clinical isolated Cunninghamella bertholletiae Z2 strain with rich cytochrome P450 enzymes (Article).

Mucormycosis is receiving much more attention because of its high morbidity and extremely high mortality rate in immunosuppressed populations. In this study, we isolated a Cunnignhamella bertholletiae Z2 strain from a skin lesion of a 14 year, 9 months old girl with acute lymphoblastic leukemia who die of infection from the Z2 strain. Genome sequencing was performed after isolation and amplification of the Z2 strain to reveal potential virulence factors and pathogenic mechanisms. The results showed that the genome size of the Z2 strain is 30.9 Mb with 9213 genes. Mucoral specific virulence factor genes found are ARF, CalN, and CoTH, while no gliotoxin biosynthesis gene cluster was found, which is a known virulence factor in Aspergillus fumigatus adapted to the environment. The Z2 strain was found to have 69 cytochrome P450 enzymes, which are potential drug resistant targets. Sensitivity testing of Z2 showed it was only inhibited by amphotericin B and posaconazole. Detailed genomic information of the C. bertholletiae Z2 strain may provide useful data for treatment.

Chemical constitutes from Tuber indicum with immunosuppressive activity uncovered by transcriptome analysis.

Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model.

Nitric oxide controls shoot meristem activity via regulation of DNA methylation.

Despite the importance of Nitric Oxide (NO) as signaling molecule in both plant and animal development, the regulatory mechanisms downstream of NO remain largely unclear. Here, we show that NO is involved in Arabidopsis shoot stem cell control via modifying expression and activity of ARGONAUTE 4 (AGO4), a core component of the RNA-directed DNA Methylation (RdDM) pathway. Mutations in components of the RdDM pathway cause meristematic defects, and reduce responses of the stem cell system to NO signaling. Importantly, we find that the stem cell inducing WUSCHEL transcription factor directly interacts with AGO4 in a NO dependent manner, explaining how these two signaling systems may converge to modify DNA methylation patterns. Taken together, our results reveal that NO signaling plays an important role in controlling plant stem cell homeostasis via the regulation of de novo DNA methylation.

Highly Stable Amide-Functionalized Zirconium-Organic Frameworks: Synthesis, Structure, and Methane Storage Capacity.

With the development of crystalline porous materials toward methane storage, the stability issue of metal-organic framework (MOF) materials has caused great concern despite high working capacity. Considering the high stability of zirconium-based MOFs and effective functions of amide groups toward gas adsorption, herein, a series of UiO-66 type of Zr-MOFs, namely, Zr-fcu-H/F/CH3/OH, were successfully designed and synthesized by virtue of amide-functionalized dicarboxylate ligands bearing distinct side groups (i.e., -H, -F, -CH3, and -OH) and ZrCl4 in the presence of trifluoroacetic acid as the modulator. Single-crystal X-ray diffraction and topology analyses reveal that these compounds are archetypal fcu MOFs encompassing octahedral and tetrahedral cages, respectively. The N2 sorption isotherms and acid-base stability tests demonstrate that the materials possess not only relatively high surface areas, pore volumes, and appropriate pore sizes but also great hydrolytic stabilities ranging pH = 3-11. Furthermore, the volumetric methane storage working capacities of Zr-fcu-H, Zr-fcu-F, Zr-fcu-CH3, and Zr-fcu-OH at 298/273 K and 80 bar are 187/217, 175/193, 167/187, and 154/171 cm3 (STP) cm-3, respectively, which indicate that the zirconium-based crystalline porous materials are capable of storing relatively high amounts of methane.

A Novel Zn2Cys6 Transcription Factor, TopC, Positively Regulates Trichodin A and Asperpyridone A Biosynthesis in Tolypocladium ophioglossoides.

Asperpyridone A represents an unusual class of pyridone alkaloids with demonstrated potential for hypoglycemic activity, primarily by promoting glucose consumption in HepG2 cells. Trichodin A, initially isolated from the marine fungus Trichoderma sp. strain MF106, exhibits notable antibiotic activities against Staphylococcus epidermidis. Despite their pharmacological significance, the regulatory mechanisms governing their biosynthesis have remained elusive. In this investigation, we initiated the activation of a latent gene cluster, denoted as "top", through the overexpression of the Zn2Cys6 transcription factor TopC in Tolypocladium ophioglossoides. The activation of the top cluster led to the biosynthesis of asperpyridone A, pyridoxatin, and trichodin A. Our study also elucidated that the regulator TopC exerts precise control over the biosynthesis of asperpyridone A and trichodin A through the detection of protein-nucleic acid interactions. Moreover, by complementing these findings with gene deletions involving topA and topH, we proposed a comprehensive biosynthesis pathway for asperpyridone A and trichodin A in T. ophioglossoides.

Daptomycin production enhancement by ARTP mutagenesis and fermentation optimization in Streptomyces roseosporus.

AIMS: We evaluated whether the randomness of mutation breeding can be regulated through a double-reporter system. We hope that by establishing a new precursor feeding strategy, the production capacity of industrial microorganisms after pilot scale-up can be further improved. METHODS AND RESULTS: In this study, the industrial strain Streptomyces roseosporus L2796 was used as the starter strain for daptomycin production, and a double-reporter system with the kanamycin resistance gene Neo and the chromogenic gene gusA was constructed to screen for high-yield strain L2201 through atmospheric and room temperature plasma (ARTP). Furthermore, the composition of the culture medium and the parameters of precursor replenishment were optimized, resulting in a significant enhancement of the daptomycin yield of the mutant strain L2201(752.67 mg/l). CONCLUSIONS: This study successfully screened a high-yield strain of daptomycin through a double-reporter system combined with ARTP mutation. The expression level of two reporter genes can evaluate the strength of dptEp promoter, which can stimulate the expression level of dptE in the biosynthesis of daptomycin, thus producing more daptomycin. The developed multi-stage feeding rate strategy provides a novel way to increase daptomycin in industrial fermentation.

Production improvement of FK506 in Streptomyces tsukubaensis by metabolic engineering strategy.

AIMS: Study of the effect of isoleucine on the biosynthesis of FK506 and modification of its producing strain to improve the production of FK506. METHODS AND RESULTS: Metabolomics analysis was conducted to explore key changes in the metabolic processes of Streptomyces tsukubaensis Δ68 in medium with and without isoleucine. In-depth analysis revealed that the shikimate pathway, methylmalonyl-CoA, and pyruvate might be the rate-limiting factors in FK506 biosynthesis. Overexpression of involved gene PCCB1 in S. tsukubaensis Δ68, a high-yielding strain Δ68-PCCB1 was generated. Additionally, the amino acids supplement was further optimized to improve FK506 biosynthesis. Finally, FK506 production was increased to 929.6 mg L-1, which was 56.6% higher than that in the starter strain, when supplemented isoleucine and valine at 9 and 4 g L-1, respectively. CONCLUSIONS: Methylmalonyl-CoA might be the key rate-limiting factors in FK506 biosynthesis and overexpression of the gene PCCB1 and further addition of isoleucine and valine could increase the yield of FK506 by 56.6%.

Yersiniabactin-Producing E. coli Induces the Pyroptosis of Intestinal Epithelial Cells via the NLRP3 Pathway and Promotes Gut Inflammation.

The high-pathogenicity island (HPI) was initially identified in Yersinia and can be horizontally transferred to Escherichia coli to produce yersiniabactin (Ybt), which enhances the pathogenicity of E. coli by competing with the host for Fe3+. Pyroptosis is gasdermin-induced necrotic cell death. It involves the permeabilization of the cell membrane and is accompanied by an inflammatory response. It is still unclear whether Ybt HPI can cause intestinal epithelial cells to undergo pyroptosis and contribute to gut inflammation during E. coli infection. In this study, we infected intestinal epithelial cells of mice with E. coli ZB-1 and the Ybt-deficient strain ZB-1Δirp2. Our findings demonstrate that Ybt-producing E. coli is more toxic and exacerbates gut inflammation during systemic infection. Mechanistically, our results suggest the involvement of the NLRP3/caspase-1/GSDMD pathway in E. coli infection. Ybt promotes the assembly and activation of the NLRP3 inflammasome, leading to GSDMD cleavage into GSDMD-N and promoting the pyroptosis of intestinal epithelial cells, ultimately aggravating gut inflammation. Notably, NLRP3 knockdown alleviated these phenomena, and the binding of free Ybt to NLRP3 may be the trigger. Overall, our results show that Ybt HPI enhances the pathogenicity of E. coli and induces pyroptosis via the NLRP3 pathway, which is a new mechanism through which E. coli promotes gut inflammation. Furthermore, we screened drugs targeting NLRP3 from an existing drug library, providing a list of potential drug candidates for the treatment of gut injury caused by E. coli.

Reliability, validity, and sensitivity of short-form 36 health survey (SF-36) in patients with sick sinus syndrome.

Patients with sick sinus syndrome (SSS) experience a decrease in health-related quality of life (HRQoL), but there is currently no scale available to measure their unpleasant symptoms. The Short Form 36 Health Survey (SF-36) is a commonly used scale to assess HRQoL. In this study, we aimed to evaluate the reliability, validity, and sensitivity of SF-36 in patients with SSS. The sample included 199 eligible participants. We estimated the reliability through test-retest reliability, internal consistency, and split-half reliability. To examine the validity of the questionnaire, confirmatory factor analysis, convergent validity, and discriminant validity were conducted. Sensitivity was determined by the differences in age (cutoff 65 years) and New York Heart Association class. The intraclass correlational coefficients scores showed high test-retest reliability (intraclass correlational coefficients > 0.7). The overall Cronbach α was 0.87 (8 scales range: 0.85-0.87), showing good internal consistency reliability. The split-half reliability coefficient of the SF-36 is 0.814, indicating good reliability. Factor analysis showed that SF-36 subscales could be drawn into 6 components that explain 61% of the total variance. Results of model fit indicate comparative fit index = 0.9, incremental fit index = 0.92, Turker-Lewis index = 0.90, approximate root mean square error = 0.07, and normalized root mean square residual = 0.06. Convergent validity and discriminative validity showed adequate results. Comparison of different ages and New York Heart Association class groups showed statistical significance on most SF-36 subscales. We confirmed the SF-36 as a valid instrument for evaluating HRQoL patients with SSS. The reliability, validity, and sensitivity of SF-36 are acceptable for patients with SSS.

Identification and Characterization of a New Regulator, TagR, for Environmental Stress Resistance Based on the DNA Methylome of Streptomyces roseosporus.

DNA methylation is a defense that microorganisms use against extreme environmental stress, and improving resistance against environmental stress is essential for industrial actinomycetes. However, research on strain optimization utilizing DNA methylation for breakthroughs is rare. Based on DNA methylome analysis and KEGG pathway assignment in Streptomyces roseosporus, we discovered an environmental stress resistance regulator, TagR. A series of in vivo and in vitro experiments identified TagR as a negative regulator, and it is the first reported regulator of the wall teichoic acid (WTA) ABC transport system. Further study showed that TagR had a positive self-regulatory loop and m4C methylation in the promoter improved its expression. The ΔtagR mutant exhibited better hyperosmotic resistance and higher decanoic acid tolerance than the wild type, which led to a 100% increase in the yield of daptomycin. Moreover, enhancing the expression of the WTA transporter resulted in better osmotic stress resistance in Streptomyces lividans TK24, indicating the potential for wide application of the TagR-WTA transporter regulatory pathway. This research confirmed the feasibility and effectiveness of mining regulators of environmental stress resistance based on the DNA methylome, characterized the mechanism of TagR, and improved the resistance and daptomycin yield of strains. Furthermore, this research provides a new perspective on the optimization of industrial actinomycetes. IMPORTANCE This study established a novel strategy for screening regulators of environmental stress resistance based on the DNA methylome and discovered a new regulator, TagR. The TagR-WTA transporter regulatory pathway improved the resistance and antibiotic yield of strains and has the potential for wide application. Our research provides a new perspective on the optimization and reconstruction of industrial actinomycetes.

Hemolysin Co-Regulatory Protein 1 Enhances the Virulence of Clinically Isolated Escherichia coli in KM Mice by Increasing Inflammation and Inducing Pyroptosis.

Hemolysin-coregulated protein 1 (Hcp1) is an effector released by the type VI secretion system (T6SS) in certain pathogenic strains of Escherichia coli (E. coli) that causes apoptosis and contributes to the development of meningitis. The exact toxic consequences of Hcp1 and whether it intensifies the inflammatory response by triggering pyroptosis are yet unknown. Here, utilizing the CRISPR/Cas9 genome editing method, we removed the gene expressing Hcp1 from wild-type E. coli W24 and examined the impact of Hcp1 on E. coli virulence in Kunming (KM) mice. It was found that Hcp1-sufficient E. coli was more lethal, exacerbating acute liver injury (ALI) and acute kidney injury (AKI) or even systemic infections, structural organ damage, and inflammatory factor infiltration. These symptoms were alleviated in mice infected with W24Δhcp1. Additionally, we investigated the molecular mechanism by which Hcp1 worsens AKI and found that pyroptosis is involved, manifested as DNA breaks in many renal tubular epithelial cells. Genes or proteins closely related to pyroptosis are abundantly expressed in the kidney. Most importantly, Hcp1 promotes the activation of the NLRP3 inflammasome and the expression of active caspase-1, thereby cleaving GSDMD-N and accelerating the release of active IL-1ß and ultimately leading to pyroptosis. In conclusion, Hcp1 enhances the virulence of E. coli, aggravates ALI and AKI, and promotes the inflammatory response; moreover, Hcp1-induced pyroptosis is one of the molecular mechanisms of AKI.

SOCS3 protein expression predicts the responses of advanced non-small cell lung cancer patients to platinum-based chemotherapy.

Background: This study sought to assess the relationship between suppressor of cytokine signaling 3 (SOCS3) expression, SOCS3 promoter methylation status, and platinum-based chemotherapy responses in advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 400 advanced NSCLC patients with inoperable disease were enrolled in this study. All the patients underwent platinum-based chemotherapy treatment, and the clinical and prognostic outcomes of these patients were analyzed. The SOCS3 protein expression and SOCS3 promoter methylation status of the tumor tissues in these patients were also tested by immunohistochemistry and polymerase chain reaction (PCR), respectively. In addition, we knocked down SOCS3 expression via small-interfering RNA (siRNA) in the lung cancer cell lines and conducted in vitro analyses to examine cell viability and apoptosis. Results: Patients with higher expression levels of SOCS3 were found to have a lower average tumor stage, higher average tumor differentiation, and higher rates of positive chemotherapy responses than those with lower expression levels of SOCS3. SOCS3 promoter methylation was also found to be correlated with chemotherapy responses in these patients. In the prognostic analyses, only SOCS3 expression, but not SOCS3 promoter methylation, was found to be predictive of outcomes in advanced NSCLC patients. We also found that the pro-apoptotic effects of SOCS3 were mediated by the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways in the lung cancer cells. Conclusions: Currently, there is a lack of reliable biomarkers for predicting the responses of NSCLC patients to chemotherapy. Our results may aid in clinical evaluations of NSCLC patients.

Comparative study of characteristic compounds of three species of truffle.

The Panxi area in Sichuan Province is the main area for the production of truffles in China, and several species of truffle are known to exist in this region. Nevertheless, it is unclear what the differences in chemical composition between the truffles are. Using an ultra-high-performance liquid chromatography quadrupole/orbitrap high-resolution mass spectrometry coupled with Compound Discoverer 3.0, we identified chemical components in three mainly known truffles from the Panxi region. Further analysis of chemical composition differences was conducted using principal component analysis, and orthogonal partial least squares discriminant analysis. Note that, 78.9% of the variance was uncovered by the principal component analysis model. As a result of the orthogonal partial least squares discriminant analysis model, the three species of truffles (Tuber pesudohimalayense, Tuber indicum, and Tuber sinense) from Panxi were better discriminated, with R2 X, R2 Y, and Q2 being 0.821, 0.993, and 0.947, respectively. In this study, 87 components were identified. T. pesudohimalayense contained significantly higher levels of nine different compounds than the other two species. Hence, it was possible to identify similarities and differences between three species of truffles from Panxi in terms of chemical composition. This can be used as a basis for quality control.

Two previously undescribed phthalides from Talaromyces amestolkiae, a symbiotic fungus of Syngnathus acus.

Amestolkins A (1) and B (2), two previously undescribed phthalides sharing the same planar structure of (1, 5-dihydroxyhexyl)-7-hydroxyisobenzofuran-1(3H)-one were isolated from Talaromyces amestolkiae. Their absolute configurations were elucidated by comprehensive analyses of spectroscopic evidences in high-resolution electrospray mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) combined with electronic circular dichroism (ECD) and NMR calculations. 1 and 2 showed anti-neuroinflammatory activity by inhibiting the gene expressions of proinflammatory factors including C-C motif chemokine ligand 2 (CCL-2), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), as well as attenuating the excretion of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells at the concentration of 30 µM.

Analysis of conjunctival sac microflora and antibiotic susceptibility testing in adolescents after wearing orthokeratology lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the bacterial flora and antibiotic susceptibility testing of conjunctival sac in adolescents after wearing orthokeratology(OK)lens.METHODS:A total of 101 adolescents aged 8 to 14 who admitted to outpatient department of Xi'an No.1 Hospital from September 2021 to August 2022 were recruited in this cross-sectional observational study. There were 51 cases wearing OK Lens(wearing group)and 50 patients not wearing contact lens(non-lens group), the right eye of all patients was selected into the group. The culture of bacterial flora in conjunctival sac between the two groups were compared, the species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the antibiotic susceptibility testing was carried out for the positive strains cultured in the wearing group.RESULTS:The positive rate of conjunctival sac bacterial cultured in the wearing group and the non-lens group was 68.6%(35/51)and 60.0%(30/50), respectively(P>0.05). In both groups, the bacteria with the highest detection rate were staphylococcus epidermidis and staphylococcus aureus. The sensitivity rates of the strains detected in the wearing group to drugs are as follows: Levofloxacin(98%), Moxifloxacin(98%), Gatifloxacin(98%), Cefuroxime(98%), Cefathiamidine(98%), Rifampicin(98%), Chloramphenicol(96%), Cefoxitin(95%), Clindamycin(80%), Gentamicin(74%), Fusidic acid(72%), Tobramycin(64%), Compound sulfamethoxazole(26%), Mezlocillin(10%), Azithromycin(6%), of which the sensitivity rate of Gram-positive cocci was 100% sensitive to Vancomycin.CONCLUSION:Gram-positive cocci are the main bacteria isolated from conjunctival sac of adolescents after wearing OK Lens. Wearing OK Lens will not significantly increase the positive rate of conjunctival sac bacterial flora. Results of antibiotic susceptibility testing may provide guidance for empirical medication in patients wearing OK lens after eye infection.

Effect of Modified Zhenwutang on Interstitial Fibrosis in Rats with Chronic Renal Failure Based on IL-6/MMP-9/COL-Ⅳ Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the modulatory effect of modified Zhenwutang on the interleukin-6 （IL-6）， matrix metallopeptidase-9（MMP-9）， type Ⅳ collagen（COL-Ⅳ） in rats with chronic renal failure （CRF） and to investigate the potential mechanism of its treatment of CRF. MethodFifty male SD rats were randomly divided into a modeling group of 40 rats and a normal group of 10 rats， and the modeling group was prepared by continuous adenine gavage for 12 weeks. After successful modelling， the modelling group was divided into the model group， the low dose （7.2 g·kg-1·d-1） group， the medium dose （14.4 g·kg-1·d-1） group， the high dose （28.8 g·kg-1·d-1） group and the Benadryl hydrochloride （10 mg·kg-1·d-1） group for gavage according to the random number table method， In the normal group and the model group， equal volume of distilled water was administered by gavage for 4 weeks. After the administration， the levels of blood creatinine （SCr）， blood urea nitrogen （BUN） and 24 h urine protein （24 h-UTP） were measured， the levels of serum IL-6 were measured by enzyme linked immunosorbent assay（ELISA）. Immunohistochemistry （IHC） was used to detect intercellular cell adhesion molecule-1 （ICAM-1）， IL-6， MMP-9， and other molecules in the rat kidney. The expression of ICAM-1 mRNA， IL-6 mRNA， MMP-9 mRNA and COL-Ⅳ mRNA in rat kidney tissues was measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression levels of ICAM-1， IL-6， MMP-9 and COL-Ⅳ in rat kidney tissues were measured by Western blot. ResultCompared with the normal group， the levels of SCr， BUN and 24 h-UTP were significantly increased in the model group （P<0.01）； the serum IL-6 level was significantly increased （P<0.01）， the tubular lumen was dilated with atrophy， the tubular epithelial cells were necrotic， swollen and vacuolated， the interstitium was infiltrated by a large number of inflammatory cells and collagen fibers were deposited， the levels of IL-6， ICAM-1 and COL-Ⅳ were strongly positive in the tubular interstitium of the model group （P<0.01）， The levels of ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA were significantly increased （P<0.01） and MMP-9 mRNA was significantly decreased （P<0.05） in the model rats. ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly increased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01） in the renal tissue， and MMP-9 protein expression was significantly decreased （P<0.01）. Compared with the model group， the 24 h-UTP， SCr and BUN levels of rats were significantly reduced after treatment with modified Zhenwutang （P<0.01）， the serum IL-6 level was significantly decreased （P<0.01）， the renal lesions of rats were significantly improved and collagen fiber deposition was reduced； the expression of IL-6， ICAM-1 and COL-Ⅳ in renal tubules and interstitium was weakened， and MMP-9 in ICAM-1 mRNA， IL-6 mRNA and COL-Ⅳ mRNA levels were significantly reduced （P<0.01） and MMP-9 mRNA levels were significantly increased （P<0.05）， ICAM-1， IL-6 and COL-Ⅳ protein expression was significantly reduced （P<0.01） and MMP-9 protein expression was significantly The expression of ICAM-1， IL-6 and COL-Ⅳ proteins was significantly decreased （P<0.01） and MMP-9 protein expression was significantly increased （P<0.01）. ConclusionModified Zhenwutang may regulate the IL-6/MMP-9/COL-Ⅳ signaling pathway， thereby reducing proteinuria， improving renal function， reducing renal pathological damage and delaying the progression of CRF interstitial fibrosis.

Association between cigarette smoking and mortality in patients with hip fracture: A systematic review and meta-analysis.

INTRODUCTION: Hip fracture is associated with substantial morbidity and mortality, especially among the elderly. Current evidence on the association between cigarette smoking and mortality in hip-fracture patients is controversial. We performed a systematic review and meta-analysis of studies on this association. METHODS: The databases Medline/PubMed, Embase, Web of Science, and Cochrane Library were searched for studies that estimated the effect of smoking on the risk of mortality in hip-fracture patients. Pooled analyses were conducted of the associations, expressed in relative risk (RR) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a funnel plot, Begg's and Egger's tests. Subgroup analyses were performed by study design, race/ethnicity, age ≥60 years, smoking status, and follow-up period. RESULTS: A total of six articles involving 3739 hip-fracture patients were included in the meta-analysis. Our results indicate that ever-active smoking was significantly associated with an increased risk of death in hip-fracture patients (pooled RR=1.26; 95% CI: 1.08-1.46). In further subgroup analysis, the risk of death was significantly higher in ever-active smokers than in never smokers in White participants (pooled RR=1.23; 95% CI: 1.05-1.44) and elderly aged ≥60 years (pooled RR=1.19; 95% CI: 1.01-1.40), with no significant association in Asian participants (pooled RR=1.42; 95% CI: 0.95-2.11). Current smokers had more risk of death than never smokers (pooled RR=1.26; 95% CI: 1.08-1.46). The association was significant in follow-up periods of ≤1 year (pooled hazard ratio, HR=1.34; 95% CI: 1.05-1.71), 3 years (pooled HR=1.22; 95% CI: 1.05-1.43), and 5 years (pooled HR=1.26; 95% CI: 1.08-1.46). CONCLUSIONS: Cigarette smoking is associated with an increased risk of mortality in hip-fracture patients, especially in elderly patients aged ≥60 years, current smokers, and White participants. With the extension of follow-up period, the effect on mortality of smoking is profound and lasting.