Precise control of microtubule disassembly in living cells.

Microtubules tightly regulate various cellular activities. Our understanding of microtubules is largely based on experiments using microtubule-targeting agents, which, however, are insufficient to dissect the dynamic mechanisms of specific microtubule populations, due to their slow effects on the entire pool of microtubules. To overcome this technological limitation, we have used chemo and optogenetics to disassemble specific microtubule subtypes, including tyrosinated microtubules, primary cilia, mitotic spindles, and intercellular bridges, by rapidly recruiting engineered microtubule-cleaving enzymes onto target microtubules in a reversible manner. Using this approach, we show that acute microtubule disassembly swiftly halts vesicular trafficking and lysosomal dynamics. It also immediately triggers Golgi and ER reorganization and slows the fusion/fission of mitochondria without affecting mitochondrial membrane potential. In addition, cell rigidity is increased after microtubule disruption owing to increased contractile stress fibers. Microtubule disruption furthermore prevents cell division, but does not cause cell death during interphase. Overall, the reported tools facilitate detailed analysis of how microtubules precisely regulate cellular architecture and functions.

KF-catalyzed direct thiomethylation of carboxylic acids with DMSO to access methyl thioesters.

With dimethyl sulfoxide (DMSO) as the methylthio source, a KF-catalyzed strategy was employed for the direct thiomethylation of carboxylic acids with DMSO for the preparation of methyl thioesters. In this process, a wide range of methyl thioesters were obtained in moderate to excellent yields. This novel strategy features the first use of DMSO as a methylthiolating agent for the construction of methyl thioesters, transition metal-free conditions, inexpensive reagents, easy workup, broad substrate scope and sustainability. Additionally, this procedure can be readily scaled up to a gram scale.

Myostain is involved in ginsenoside Rb1-mediated anti-obesity.

CONTEXT: Obesity, one of the major public health problems worldwide, has attracted increasing attention. Ginsenoside Rb1 is the most abundant active component of Panax ginseng C.A.Mey (Araliaceae) and is reported to have beneficial effects on obesity and diabetes. However, the mechanisms by which Rb1 regulates obesity remain to be explored. OBJECTIVE: This paper intends to further explore the mechanism of Rb1 in regulating obesity. MATERIALS AND METHODS: The C57BL/6 obese mice were divided into two groups: the control (CTR) and Rb1. The CTR group [intraperitoneally (ip) administered with saline] and the Rb1 group (ip administered with Rb1, 40 mg/kg/d) were treated daily for four weeks. In vitro, Rb1 (0, 10, 20, 40 µM) was added to differentiated C2C12 cells and Rb1 (0, 20, 40 µM) was added to 3T3-L1 cells. After 24 h, total RNA and protein from C2C12 cells and 3T3-L1 cells were used to detect myostatin (MSTN) and fibronectin type III domain-containing 5 (FNDC5) expression. RESULTS: Rb1 reduced the body weight and adipocyte size. Improved glucose tolerance and increased basic metabolic activity were also found in Rb1 treated mice. MSTN was downregulated in differentiated C2C12 cells, 3T3-L1 cells and adipose tissues upon Rb1 treatment. FNDC5 was increased after Rb1 treatment. However, MSTN overexpression attenuated Rb1-mediated decrease accumulation of lipid droplets in differentiated 3T3-L1 adipocytes. DISCUSSION & CONCLUSIONS: Rb1 may ameliorate obesity in part through the MSTN/FNDC5 signalling pathway. Our results showed that Rb1 can be used as an effective drug in the treatment of human obesity.

The long-term impact of a chronic total occlusion in a non-infarct-related artery on acute ST-segment elevation myocardial infarction after primary coronary intervention.

OBJECTIVES: To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality. METHODS: The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared. RESULTS: The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47-10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P < 0.01), an in-hospital Killip class ≥ 3 (OR = 4.32, 95% CI: 1.71 ~ 10.95, P < 0.01), and the presence of renal insufficiency (OR = 5.32, 95% CI: 1.49 ~ 19.01, P = 0.01), stress ulcer with gastraintestinal bleeding (SUB) (OR = 6.36, 95% CI: (1.45 ~ 28.01, P = 0.01) were significantly related the 10-year mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 (OR = 2.97,95% CI:1.46 ~ 6.03, P < 0.01) and the presence of renal insufficiency (OR = 5.61, 95% CI: 1.19 ~ 26.39, P = 0.03) were significantly related to the 10-year mortality of patients with STEMI and a CTO. CONCLUSIONS: The presence of a CTO in a non-IRA, an age ≥ 65 years, an in-hospital Killip class ≥ 3, and the presence of renal insufficiency, and SUB were independent risk predictors for the long-term mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 and renal insufficiency were independent risk predictors for the long-term mortality of patients with STEMI and a CTO.

Sonogenetic Modulation of Cellular Activities Using an Engineered Auditory-Sensing Protein.

Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterologous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also noninvasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mouse brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, our sonogenetic tools will serve as new strategies for noninvasive therapy in deep tissues.

Current Situation of Methamphetamine Abuse and Related Research Progress.

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.

Characteristics of ß-oxidative and reductive metabolism on the acyl side chain of cinnamic acid and its analogues in rats.

Cinnamic acid and its analogues (pyragrel and ozagrel) undergo chain-shortened (ß-oxidative) and reductive metabolism on acyl side chain. In this study, we characterized the ß-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues using primary rat hepatocytes, hepatic mitochondrial, and microsomal systems. A compartmental model including parent compounds and metabolites was developed to characterize in vivo ß-oxidative and reductive metabolism following an intravenous dose of parent compounds to rats. The fitted total in vivo clearance values were further compared with the in vitro values predicted by the well-stirred model. We showed that hepatic microsomal CYP450s did not catalyze ß-oxidative or reductive metabolism of the three compounds. Similar to ß-oxidation of fatty acids, ß-oxidative metabolism on their acyl side chain occurred mainly in mitochondria, which was highly dependent on ATP, CoA and NAD+. Fatty acids and NADH inhibited the ß-oxidative metabolism. Reductive metabolism occurred in both mitochondria and microsomes. Reduction in mitochondria was ATP-, CoA-, and NAD(P)H-dependent and reversible, which was suppressed by enoyl reductase inhibitor triclosan. Reduction in microsomes was ATP-, CoA-, and NADPH-dependent but little affected by triclosan. Both plasma concentrations of ß-oxidative metabolites and reductive metabolites were successfully fitted using the compartmental model. The estimated total in vivo clearance values were consistent with those predicted from hepatocytes and organelles, implicating significance of in vitro kinetics. These findings demonstrate the roles of hepatic mitochondria and microsomes in ß-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues along with their metabolic characteristics.

LncRNA HOTAIR promotes renal interstitial fibrosis by regulating Notch1 pathway via the modulation of miR-124.

AIM: To understand the mechanism of long non-coding RNA (LncRNA) HOTAIR on renal interstitial fibrosis (RIF) by regulating Notch1 pathway via the modulation of miR-124. METHODS: Unilateral ureteral occlusion (UUO) was used to construct the RIF rat model. HK-2 cells induced by TGF-ß1 were used for the in vitro experiment, which were divided into five groups: Vehicle, TGF-ß1, si-HOTAIR+TGF-ß1, miR-124 inhibitor+TGF-ß1, and si-HOTAIR+miR-124 inhibitor+TGF-ß1 groups. Quantitative real-time PCR (qRT-PCR) and Western blot were performed to detect the expression of HOTAIR, miR-124, Notch1- and epithelial-to-mesenchymal transition (EMT)-related proteins. RESULTS: Significant elevated HOTAIR and reduced miR-124 were presented in UUO rats and TGF-ß1-induced HK-2 cells in a time-dependent manner, with the increased Jagged1 (JAG1), Notch1, NICD, α-SMA and FN, as well as the decreased E-cadherin (all P < 0.05). Compared with the TGF-ß1 group, cells in the si-HOTAIR+TGF-ß1 group were remarkably declined in cell proliferation and the protein expressions of JAG1, Notch1, NICD, α-SMA, and FN, but dramatically higher in E-cadherin expression (all P < 0.05). However, in comparison with the si-HOTAIR+TGF-ß1 group, cells in the si-HOTAIR+miR-124 inhibitor+TGF-ß1 group were apparently improved in proliferation and the protein expression of JAG1, Notch1, NICD, α-SMA, and FN, but substantially reduced in the level of E-cadherin protein (all P < 0.05). CONCLUSION: Silencing lncRNA HOTAIR can up-regulate miR-124 to block Notch1 pathway, and thereby alleviating EMT and RIF, indicating HOTAIR as a potential target for RIF treatment.

Wavelength tuning of surface plasmon coupled quantum well infrared photodetectors.

A novel method of detection wavelength tuning for surface plasmon coupled quantum well infrared photodetectors (QWIPs) was demonstrated. By changing of the thickness of the top contact layer, the detection wavelength can be adjusted. The displacement of the detection wavelength is related to the effective dielectric constant of the dielectric layers in the device structure. The peak wavelength moves toward longer wavelength as the contact layer thickness decreases. With a proper match of the 2D metal hole array and the QW absorption region, the responsivity can be kept within a reasonable range for samples with different top contact layer thicknesses.

Effects of Preoperative Isokinetic Eccentric Training and Whey Protein Isolate Supplement on Quadriceps Strength and Knee Function in Patients with Anterior Cruciate Ligament Rupture.

Objective To explore the effect of preoperative isokinetic eccentric training with or not whey protein isolate supplement before operation on lower limb muscle strength and knee function in patients with anterior cruciate ligament (ACL) rupture. Methods A total of 22 male volunteers aged 18-40 years with ACL rupture were recruited in outpatient service. With randomized block design,subjects were randomly assigned to isokinetic eccentric training (IE) group and isokinetic eccentric training with whey protein isolate supplement (IE+WPI) group. The IE group received isokinetic eccentric training of the injured limb on an isokinetic dynamometer under the guidance of physiatrist in laboratory before operation. There were 3-4 sets per day with 8-10 repetitions for each set,twice a week,with at least one day between sessions. The IE+WPI group were supplied with whey protein isolate 22 g per day on the basis of isokinetic eccentric training,taking breakfast or 30-60 minutes after the training. The intervention lasted for 6 weeks. Isokinetic muscle strength of limbs,the function and laxity of knee,the circumferences of thigh and knee,and the body composition were measured before and after the treatment. Results Compared with baseline,the peak torque (PT) of isokinetic-eccentric contraction (IE group:41.0%,P=0.018;IE+WPI group:46.7%,P=0.008) and the concentric contraction (IE group:29.6%,P=0.018;IE+WPI group:38.9%,P=0.038) of quadriceps in the two training groups significantly increased after isokinetic eccentric training. The Lysholm score increased significantly in IE+WPI group compared with baseline (P=0.018). Conclusions Isokinetic eccentric training before operation for ACL rupture patients can increase the strength of quadriceps and improve the function of knees. Protein isolate supplement can improve such effect.

Recombinant IL-33 prolongs leflunomide-mediated graft survival by reducing IFN-γ and expanding CD4(+)Foxp3(+) T cells in concordant heart transplantation.

Interleukin (IL)-33 is a novel IL-1 family member, and its administration has been associated with promotion of T helper type-2 (Th2) cell activity and cytokines, particularly IL-4 and IL-5 in vivo. Recently, IL-33 was shown to increase CD4(+)Foxp3(+) regulatory T cells (Tregs) and to suppress levels of the Th1-type cytokine IFN-γ in allogeneic heart transplantation in mice. Therefore, we hypothesized that IL-33 and leflunomide (Lef) could prolong graft survival in the concordant mouse-to-rat heart transplantation model. In this model, xenografts undergo acute humoral xenograft rejection (AHXR) typically on day 3 or cell-mediated rejection approximately on day 7 if AHXR is inhibited by Lef treatment. Recipients were treated with Lef (n=6), IL-33 (n=6), IL-33 combined with Lef (n=6), or left untreated (n=6) for survival studies. Heart grafts were monitored until they stopped beating. Mouse heterotopic grafts were performed, and recipients were sacrificed on days 2 and 7 for histological and flow cytometric analyses. The combination of IL-33 and Lef significantly prolonged the grafts from 17.3±2.3 to 2.8±0.4 days, compared to untreated controls. IL-33 administration with Lef, while facilitating Th2-associated cytokines (IL-4 on day 2 but not day 7), also decreased IFN-γ on day 2 and day 7, compared with Lef treatment only. Furthermore, IL-33 with Lef administration caused an expansion of suppressive CD4(+)Foxp3(+) Tregs in rats. The IL-33 and Lef combination therapy resulted in significantly prolonged graft survival, associated with markedly decreased Th1 cells and increased IL-10 levels. In addition, the combination therapy significantly decreased the percentage of CD-45(+) B cells on days 2 and 7, compared with monotherapy. These findings reveal a new immunoregulatory property of IL-33. Specifically, it facilitates regulatory cells, particularly functional CD4(+)Foxp3(+) Tregs that underlie IL-33-mediated cardiac xenograft survival. Moreover, it can decrease Th1 cells and cytokine expression of Th1 T cells in xenograft recipients, for example IFN-γ.

Repression of flowering under a noninductive photoperiod by the HDA9-AGL19-FT module in Arabidopsis.

Posttranslational acetylation of histones is reversibly regulated by histone deacetylases (HDACs). Despite the evident significance of HDACs in Arabidopsis development, the biological roles and underlying molecular mechanisms of many HDACs are yet to be elucidated. By a reverse-genetic approach, we isolated an hda9 mutant and performed phenotypic analyses on it. In order to address the role of HDA9 in flowering, genetic, molecular, and biochemical approaches were employed. hda9 flowered early under noninductive short-day (SD) conditions and had increased expression of the floral integrator FLOWERING LOCUS T (FT) and the floral activator AGAMOUS-LIKE 19 (AGL19) compared with the wild-type. The hda9 mutation increased histone acetylation and RNA polymerase II occupancy at AGL19 but not at FT during active transcription, and the HDA9 protein directly targeted AGL19. AGL19 expression was higher under SD than under inductive long-day (LD) conditions, and an AGL19 overexpression caused a strong up-regulation of FT. A genetic analysis showed that an agl19 mutation is epistatic to the hda9 mutation, masking both the early flowering and the increased FT expression of hda9. Taken together, our data indicate that HDA9 prevents precocious flowering under SD conditions by curbing the hyperactivation of AGL19, an upstream activator of FT, through resetting the local chromatin environment.

Completing the Picture of the Roper Resonance.

We employ a continuum approach to the three valence-quark bound-state problem in relativistic quantum field theory to predict a range of properties of the proton's radial excitation and thereby unify them with those of numerous other hadrons. Our analysis indicates that the nucleon's first radial excitation is the Roper resonance. It consists of a core of three dressed quarks, which expresses its valence-quark content and whose charge radius is 80% larger than the proton analogue. That core is complemented by a meson cloud, which reduces the observed Roper mass by roughly 20%. The meson cloud materially affects long-wavelength characteristics of the Roper electroproduction amplitudes but the quark core is revealed to probes with Q(2)≳3m(N)(2).

[Effect of anterior cruciate ligament rupture on hamstring: quadriceps ratio during isokinetic knee extension and flexion at 30 degrees of flexion].

OBJECTIVE: To evaluate the change in hamstring (H):quadriceps (Q) ratio following anterior cruciate ligament (ACL) rupture during isokinetic knee extension and flexion at 30 degrees of flexion which is important for knee dynamic function. METHODS: A study was performed in 25 male complete unilateral ACL ruptures. Isokinetic concentric and eccentric quadriceps and hamstring muscle tests in both the deficient knees and intact knees were performed at 60°/s, respectively. At 30 degrees of flexion, the average torque of quadriceps and hamstring, Qe:Qc ratios (ratios of eccentric quadriceps to concentric quadriceps muscle torque), He:Hc ratios (eccentric hamstring to concentric hamstring), Hc:Qc ratios (concentric hamstring to concentric quadriceps), He:Qc ratios (eccentric hamstring to concentric quadriceps), and Hc:Qe ratios (concentric hamstring to eccentric quadriceps) were calculated. Wilcoxon matched-pairs signed-ranks test was used. RESULTS: At 30 degrees of knee flexion, a significant reduction (P<0.05) in the average torque of quadriceps was observed at concentric and eccentric 60°/s produced by the deficient-side compared with the intact side. In addition, Hc:Qc, He:Qc, and Qe:Qc significantly increased on the ACL-deficient side. CONCLUSION: The change in H :Q ratio in the mode of isokinetic 60°/s at 30 degrees of knee flexion might therefore be a new tool to objectively document muscle function in ACL-deficient knee.

Ozone dissociation to oxygen affected by Criegee intermediate.

The detailed potential energy surfaces for the reactions of Criegee intermediate (CI, H2COO) and formaldehyde (H2CO) with ozone (O3) have been investigated at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-311++G(2d,2p) level of theory, respectively. New alternative reaction mechanisms, to the one previously proposed (J. Phys. Chem. Lett. 2013, 4, 2525) have been found. The lower barrier of the new mechanism shows that it is easy for H2COO + O3 to dissociate to formaldehyde and oxygen. For the reactions of H2CO with O3 to produce H2COO and O2, we find relatively high energy barriers, which makes the ozone dissociation to oxygen unlikely to be catalyzed by CI.

Systemic inflammation in patients with chronic obstructive pulmonary disease undergoing percutaneous coronary intervention.

BACKGROUND AND OBJECTIVE: Systemic inflammation plays an important role in both chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). The purpose of the present study was to assess the association of high-sensitivity C-reactive protein (hs-CRP), a biomarker of systemic inflammation, with in-hospital outcomes in patients with COPD undergoing percutaneous coronary intervention (PCI). METHODS: A total of 378 patients with COPD who were treated with PCI from January 2007 through January 2012, were divided into two groups according to hs-CRP level at admission. Demographics, clinical, angiographic data and in-hospital outcomes were compared. RESULTS: Patients with elevated hs-CRP (≥3 mg/L) were more likely to be female and current smokers, had more severe airflow limitation, more hypertension, diabetes and cardiac dysfunction and had increased incidence of three-vessel disease and more type C lesions. Subjects with elevated hs-CRP were also less likely to have been prescribed with statins and B-blockers, perhaps. Rate of in-hospital composite major adverse cardiovascular events (MACEs) was higher (15.5% vs. 8.2%, P = 0.041) and hospital stay was longer (8.2 ± 2.0 vs. 7.5 ± 1.7 days, P < 0. 001) in patients with elevated hs-CRP. A combined analysis of MACE on the basis of airflow limitation and hs-CRP showed an exaggerated hazard ratio in the presence of both severe airflow limitation and elevated hs-CRP. In a multivariate analysis, elevated periprocedural hs-CRP was independently related with MACEs and hospital stay. CONCLUSIONS: Elevated periprocedural hs-CRP is independently and additively related with increased incidence of in-hospital adverse outcomes in COPD patients undergoing PCI.

[Prenatal screening for major fetal heart defects by training sonographers in township hospitals and county health centers: a feasibility study].

OBJECTIVE: To explore the feasibility of screening for major fetal heart disease by training sonographers in township or county level hospitals. METHODS: Training of B ultrasound scan for congenital heart defects was given to the sonographers from one county hospital, and thirteen township hospitals (or the district hospitals), and training of fetal echocardiography was given to sonographers from four city/county hospitals. The trained sonographers who had passed the examinations and had obtained qualifications after six months of independent practice began to screen fetal congenital heart defects. To evaluate the effectiveness, sensitivity and specificity of screening was calculated by using the diagnosis of expert neonatal/fetal echocardiographers as the gold standard. RESULTS: A total of 3 425 fetuses received one fetal B ultrasound screening, one fetal echocardiography and one neonatal echocardiography from April 1, 2004 to December 31, 2005. One hundred and sixty-five B ultrasound screening images (4.9%) from township hospitals and fifty-six fetal echocardiography images (1.7%) from county or city centers couldn't be reviewed because of poor quality. The sensitivity of fetal B ultrasound screening in the township and county hospitals was 30% and 0, and the specificity 93.3% and 99.9%, respectively. Nine fetuses with a major congenital heart disease were eventually found by the trained sonographers, and two cases were misdiagnosed and two unnoticed. The total sensitivity and specificity of fetal echocardiography were 81.8% and 99.9%, respectively. The sensitivity in the county and city hospitals was 66.7% and 100%, respectively. The specificity in the county and city hospitals was 99.9% and 100%, respectively. CONCLUSION: Under the current circumstances, township hospitals are unable to perform effective fetal cardiac screening. Screening on fetal congenital heart disease is suggested to be taken by trained sonographers in county and city level medical centers.

[Effect of zhenqing recipe on non-alcoholic fatty liver in type 2 diabetes rats and the expression of SIK1].

OBJECTIVE: To observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats. METHODS: A rat model of type 2 diabetes was established by high fat/sucrose diet combined with intraperitoneal injection of small dose streptozotocin (STZ) . Modeled rats were randomly divided into the model group, the ZQR group, and the metformin group, 8 in each group. Eight rats were recruited as a normal control group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150 mg/kg was administered to rats in the metformin group by gastrogavage. Equal volume of distilled water was administered to rats in the normal control group and the model group. All medication lasted for 12 weeks. The levels of fasting blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected. The body weight and wet liver weight were weighed, and the liver weight index calculated. The liver TG content was measured. The pathological changes of liver and the expression of SIK1 were observed by HE staining and immunohistochemistry. The mRNA and protein expression of SIK1 and SREBP-1c were detected using RT-PCR and Western blot. RESULTS: Compared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight index, and liver TG contents significantly increased (P < 0.01); liver steatosis was severe, the mRNA and protein expression of SIK1 obviously decreased (P < 0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver weight index significantly decreased, liver TG contents significantly decreased, the mRNA and protein expression of SIK1 obviously increased, while mRNA and protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological changes were also improved. All the indices were improved more in the ZQR group (all P < 0.05). CONCLUSION: In this experiment, we found that the expression of SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at mRNA and protein levels.

[Accuracy and clinical efficacy of robot-assisted transiliac-transsacral screw placement for posterior pelvic ring fractures].

OBJECTIVE: To explore accuracy and clinical effect of robot-assisted implantation of sacroiliac penetrating screw in orthopedic surgery for posterior pelvic ring fracture. METHODS: The clinical data of 24 patients with posterior pelvic ring fracture treated with robot-assisted sacroiliac penetration screws from August 2022 to August 2023 were retrospectively analyzed, including 10 males and 14 females; aged from 21 to 73 years old with an average of (49.29±14.48) years old;according to Tile pelvic fractures, 13 patients were type B and 11 were type C. The effect of screw placement was evaluated according to Gras criteria based on postoperative CT scan results. At the final follow-up, fracture healing was evaluated according to Matta score, and functional recovery was evaluated by Majeed score. RESULTS: All patients were followed up for 3 to 13 months with an average of (6.00±3.28) months. Totally 36 sacroiliac penetrating screws, 18 S1 penetrating screws, 18 S2 penetrating screws were inserted, a total of 29 were excellent and 7 good according to Gras standard. Screw adjustment times was 0.00 (0.00, 0.75) times. At the final follow-up, Matta score was excellent in 18 patients, 5 good and 1 moderate, and the maximum displacement distance was 2.55 (0.00, 5.65) mm. Majeed score was 84.37±8.38, 15 patients were excellent, 7 good and 2 moderate. CONCLUSION: Robot could accurately and safely assist in the placement of sacroiliac joint screws for the treatment of posterior pelvic ring fractures, and promote postoperative functional recovery of patients.

Modulatory Effects of XIAOPI Formula on CXCL1 and Selected Outcomes in Triple-Negative Breast Cancer: A Randomized Controlled Clinical Trial.

Background: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients' emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown. Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores. Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials. Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.