Anlotinib Attenuates Liver Fibrosis by Regulating the Transforming Growth Factor ß1/Smad3 Signaling Pathway.

BACKGROUND: Hepatic stellate cell hyperactivation is a central link in liver fibrosis development, transforming growth factor ß1 (TGF-ß1) is a key activator of HSCs. AIMS: This study investigated whether anlotinib attenuates CCl4 induced liver fibrosis in mice and explored its antifibrotic mechanism. METHODS: We used the human hepatic stellate cell line LX-2 for in vitro assays and used TGF-ß1 to induce hepatic fibrosis in LX-2 cells. We analyzed cytotoxicity using a cell-counting kit-8 and transwell chambers to detect the migratory ability of LX-2 cells. Western blotting was used to detect the protein levels of collagen type I, α-smooth muscle actin, and p-Smad3. In addition, mice with CCl4-induced hepatic fibrosis were used as in vivo models. Histopathological examination was performed using H&E staining, Masson's trichrome staining, and immunohistochemistry. RESULTS: Anlotinib significantly reversed TGF-ß1-induced protein levels of Col I, α-SMA and p-Smad3 and inhibits migratory and proliferative abilities in vitro using LX-2 cells. CCl4 cause F4 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 12 to 14 (Ishak), a mean ALT measurement of 130 U/L and a mean measurement AST value of 119 U/L in mice. However, the CCl4-induced changes were markedly attenuated by anlotinib treatment, which returned to F2 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 4 to 6 (Ishak), a mean ALT measurement of 40 U/L and a mean measurement AST value of 56 U/L in mice. CONCLUSIONS: Our results suggest that anlotinib-mediated suppression of liver fibrosis is related to the inhibition of TGF-ß1 signaling pathway. Hepatic stellate cell hyper activation is a central link in liver fibrosis development, transforming growth factor ß1 is a key activator of HSCs. Anlotinib is a multi-targeted tyrosine kinase inhibitor that has similar targets to nintedanib, a clinically used anti-pulmonary fibrosis drug. Our study demonstrates an FDA-approved drug-anlotinib-that could prevent liver fibrosis and inflammation. Experiments in cell cultures and mice show that anlotinib can inhibit the activation of hepatic stellate cells by down-regulating the TGFß1/smad3 pathway, thereby reversing liver fibrosis. In animal experiments, anlotinib showed protective effects on the CCl4-induced liver damage, including ameliorating liver inflammation, reversing liver fibrosis and reducing liver enzymes. This is a very good signal, anlotinib may be useful for halting or reversing the progression of liver fibrosis and could be employed in the development of novel therapeutic drugs for the management of chronic liver diseases.

Long noncoding RNA SNHG9 facilitates growth of glioma stem-like cells via miR-326/SOX9 axis.

BACKGROUND: Glioma stem-like cells (GSCs) are greatly responsible for the progression of glioma. Long noncoding RNAs (lncRNAs) play an important role in glioma tumor progression. This study aims to explore the role and underlying mechanism of lncRNA SNHG9 in regulating GSC cell growth. METHODS: GSCs were obtained from glioma cells (U87 and U251) and referred to as GSC-87 and GSC-251, respectively. The interactions between miR-326 and SNHG9 or SOX9 were analyzed using luciferase reporter assay. Cell growth of GSCs was evaluated by EdU assay and sphere formation assay. RESULTS: SNHG9 expression was significantly higher in GSC-87 and GSC-251 cells than in U87 and U251 cells. SNHG9 overexpression promoted GSC cell growth, whereas SNHG9 knockdown inhibited GSC cell growth. Mechanistically, SNHG9 acted as a competitive endogenous RNA of miR-326 to elevate the expression of SOX9, a direct target of miR-326. Moreover, transfection with miR-326 inhibitor counteracted SNHG9 knockdown-mediated inhibition of GSC cell growth. CONCLUSIONS: SNHG9 facilitates growth of GSCs via the miR-326/SOX9 axis. This study provides a promising therapeutic target for glioma treatment.

Ionic-Strength Responsive Zwitterionic Copolymer Hydrogels with Tunable Swelling and Adsorption Behaviors.

In this work, we studied the swelling behavior and adsorption behavior of zwitterionic copolymer hydrogels, which were prepared via the free radical copolymerization of sulfobetaine methacrylate (SBMA) and other monomers including sodium p-styrenesulfonate (NaSS), acrylic acid, N-isopropylacrylamide, and 2-(dimethylamino) ethyl methacrylate. The PSBMA hydrogel showed increased swelling ratio with the increase of ionic strength at the same temperature, and the swelling process reflected endothermicity. Interestingly, the PSBMA-NaSS hydrogels collapsed when the ionic strength increased because the ions can weaken the repulsive interaction of the anionic groups of PNaSS. In addition, the PSBMA-NaSS showed high adsorption of methylene blue (760 mg/g). The zwitterionic hydrogels have potential to be used as an adsorbent in the field of wastewater treatment.

Design of Carrageenan-Based Heparin-Mimetic Gel Beads as Self-Anticoagulant Hemoperfusion Adsorbents.

The currently used hemoperfusion adsorbents such as activated carbon and ion-exchange resin show dissatisfactory hemocompatibility, and a large dose of injected heparin leads to the increasing cost and the risk of systematic bleeding. Natural polysaccharide adsorbents commonly have good biocompatibility, but their application is restricted by the poor mechanical strength and low content of functional groups. Herein, we developed an efficient, self-anticoagulant and blood compatible hemoperfusion adsorbent by imitating the structure and functional groups of heparin. Carrageenan and poly(acrylic acid) (PAA) cross-linked networks were built up by the combination of phase inversion of carrageenan and post-cross-linking of AA, and the formed dual-network structure endowed the beads with improved mechanical properties and controlled swelling ratios. The beads exhibited low protein adsorption amounts, low hemolysis ratios, low cytotoxicity, and suppressed complement activation and contact activation levels. Especially, the activated partial thromboplastin time, prothrombin time, and thrombin time of the gel beads were prolonged over 13, 18, and 4 times than those of the control. The self-anticoagulant and biocompatible beads showed good adsorption capacities toward exogenous toxins (560.34 mg/g for heavy metal ions) and endogenous toxins (14.83 mg/g for creatinine, 228.16 mg/g for bilirubin, and 18.15 mg/g for low density lipoprotein (LDL)), thus, highlighting their potential usage for safe and efficient blood purification.

Covalent deposition of zwitterionic polymer and citric acid by click chemistry-enabled layer-by-layer assembly for improving the blood compatibility of polysulfone membrane.

Development of blood compatible membranes is critical for biomedical applications. Zwitterionic polymers have been proved to be resistant to nonspecific protein adsorption and platelet adhesion. In this work, two kinds of zwitterionic copolymers bearing alkynyl and azide groups are synthesized by atom transfer radical polymerization (ATRP) and subsequent reactions, namely alkynyl-poly(sulfobetaine methacrylate) (alkynyl-PSBMA) and azide-poly(sulfobetaine methacrylate) (azide-PSBMA). The copolymers are directly used to modify azido-functionalized polysulfone (PSf-N3) membrane via click chemistry-enabled layer-by-layer (LBL) assembly. Alkynyl-citric acid is then clicked onto the membrane when the outermost layer was azide-PSBMA. The chemical compositions, surface morphologies, and hydrophilicity of the zwitterionic polymer and citric acid multilayer modified membranes are characterized. The composite multilayer is resistant to protein adsorption and platelet adhesion and also prolongs clotting times, indicating that the blood compatibility is improved. Moreover, after clicking the small molecule anticoagulant alkynyl-citric acid onto the outermost of the zwitterionic multilayer, the membrane shows further improved anticoagulant property. The deposition of zwitterionic polymer and citric acid via click chemistry-enabled LBL assembly can improve the blood compatibility of the PSf membrane.

Visual outcome of 25 Gauge vitrectomy for acute post operative infectious endophthalmitis.

BACKGROUND: The correlation between the change in foveal thickness measured using optical coherence tomography (OCT) following surgery for infectious endophthalmitis and preoperative and postoperative visual acuity is uncertain, and there are few pertinent studies on this topic. OBJECTIVE: We explored the variations in macular thickness using OCT after emergency vitrectomy for post-cataract infectious endophthalmitis and the relationship between macular thickness with changes in visual function. METHODS: We included 10 cases of post-cataract infectious endophthalmitis. Each patient underwent 25-G vitrectomy. RESULTS: The infection in all 10 patients was under control and visual function improved. Postoperative vitreous humor culture was positive in 8 patients, including 7 cases of coagulase-negative Staphylococcus epidermidis and 1 case of Lactobacillus acidophilus. The average age of these 10 patients was 71.60 ± 8.71 years (P< 0.05, two-tailed). There was no significant correlation between time 2 (the time of onset after cataract surgery) and visual prognosis. The average time 1 (the time of the vitrification surgery caused by the onset of the disease) was 1.45 ± 0.76 days (P< 0.05, two-tailed). The postoperative 3dVA ranged from 0.20 to 3.00, with an average visual acuity of 1.87 ± 1.12, which was superior to the preoperative value (P< 0.01, two-tailed). The correlation between the post3dVA and post 1mVA was significant. The post 1mVA ranged from 0.05 to 2.20, with an average visual acuity of 0.94 ± 0.74 (P< 0.05, two-tailed). The correlation between post 1mVA and post3mVA was significant. Also, paired t-tests comparing preoperative and postoperative visual acuity revealed a significant correlation (P< 0.05, two-tailed). The post3mVA was 0-1.00 with an average visual acuity of 0.44 ± 0.41. The postoperative foveal thickness ranged from 176.00 to 514.00 µm, with an average thickness of 281.10 ± 113.12 µm. CONCLUSION: Emergency 25-G minimally invasive vitrectomy can improve visual acuity and decrease the reoperation rate for patients who have acquired post-cataract infectious endophthalmitis. There were significant correlations between age, disease onset to operation time, preoperative and postoperative visual acuity, and postoperative macular thickness.

The efficacy and safety of sintilimab combined with chemotherapy as the first-line treatment for metastatic esophageal squamous cell carcinoma.

Immunotherapy is a new treatment option for patients with esophageal squamous cell carcinoma (ESCC). However, no study has investigated the efficacy and safety of sintilimab combined with nanoparticle albumin-bound paclitaxel (Nab-PTX) and platinum as first-line treatment for metastatic ESCC. In this retrospective study, eligible patients with metastatic ESCC were administered sintilimab plus Nab-PTX, cisplatin, or nedaplatin for up to 4 to 6 cycles. Subsequently, patients without progressive disease (PD) continued to receive sintilimab every 3 weeks as maintenance treatment until unacceptable toxicity, PD, withdrawal of consent, or for up to 2 years. The primary endpoint was the objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. A total of 22 patients diagnosed with metastatic ESCC were enrolled, 1 patient reached a complete response (CR), 15 patients achieved a partial response (PR), 4 patients had stable disease, and 2 had PD. The ORR was 72.7% (16/22) and the DCR was 90.9% (20/22). The time to response was 1.9 months (95% confidence interval [CI]:1.7-2.2 months). The median PFS was 8.9 months (95% CI, 7.1-10.7 months), and the median OS was 19.0 months. Exploratory biomarker analysis revealed that lactic dehydrogenase (LDH) was a potential marker for OS, and patients with high LDH levels had shorter mOS (13.0 months, 95% CI:7.5-18.5 months). Treatment-related adverse events (AEs) occurred in 21 patients (95.5%), most of which were grade 1 or 2. No treatment-related deaths occurred in this study. The results of this study suggested that sintilimab combined with Nab-PTX and platinum in patients with metastatic ESCC had a significantly high ORR and encouraging mPFS and mOS. LDH was a potential marker for OS, and the safety profile was manageable.

Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment.

Introduction: The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir. Methods: A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development. Results: Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment. Discussion: In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Aroma volatile compounds from two fresh pineapple varieties in China.

Volatile compounds from two pineapples varieties (Tainong No.4 and No.6) were isolated by headspace solid phase microextraction (HS-SPME) and identified and quantified by gas chromatography-mass spectrometry (GC/MS). In the Tainong No. 4 and No. 6 pineapples, a total of 11 and 28 volatile compounds were identified according to their retention time on capillary columns and their mass spectra, and quantified with total concentrations of 1080.44 µg·kg(-1) and 380.66 µg·kg(-1) in the Tainong No.4 and No. 6 pineapples, respectively. The odor active values (OAVs) of volatile compounds from pineapples were also calculated. According to the OAVs, four compounds were defined as the characteristic aroma compounds for the Tainong No. 4 pineapple, including furaneol, 3-(methylthio)propanoic acid methyl ester, 3-(methylthio)propanoic acid ethyl ester and δ-octalactone. The OAVs of five compounds including ethyl-2-methylbutyrate, methyl-2-methylbutyrate, 3-(methylthio)propanoic acid ethyl ester, ethyl hexanoate and decanal were considered to be the characteristic aroma compounds for the Tainong No. 6 pineapple.

Recombinant human thrombopoietin treatment in patients with chronic liver disease-related thrombocytopenia undergoing invasive procedures: A retrospective study.

BACKGROUND: Chronic liver disease (CLD) related thrombocytopenia increases the risk of bleeding and poor prognosis. Many liver disease patients require invasive procedures or surgeries, such as liver biopsy or endoscopic variceal ligation, and most of them have lower platelet counts, which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders. Unfortunately, there is no defined treatment modality for CLD-induced thrombocytopenia. Recombinant human thrombopoietin (rhTPO) is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy; however, there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia. AIM: To evaluate the efficacy of rhTPO in the treatment of patients with CLD-associated thrombocytopenia undergoing invasive procedures. METHODS: All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021. Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia. Adverse events related to treatment, such as bleeding, thrombosis, and disseminated intravascular coagulation, were also investigated. RESULTS: Among the enrolled patients, 78 (78%) showed a platelet count increase after rhTPO use, while 22 (22%) showed no significant change in platelet count. The mean platelet count after rhTPO treatment in all patients was 101.53 ± 81.81 × 109/L, which was significantly improved compared to that at baseline (42.88 ± 16.72 × 109/L), and this difference was statistically significant (P < 0.001). In addition, patients were further divided into three subgroups according to their baseline platelet counts (< 30 × 109/L, 30-50 × 109/L, > 50 × 109/L). Subgroup analyses showed that the median platelet counts after treatment were significantly higher (P < 0.001, all). Ninety (90%) patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO. No serious adverse events related to rhTPO treatment were observed. Overall, rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia. CONCLUSION: rhTPO can improve platelet count, reduce the risk of bleeding, and decrease the platelet transfusion rate, which may promote the safety of invasive procedures and improve overall survival of patients with CLD.

[Two-photon sensors for proton derived from 7-pyridinylbenzo[c] [1,2,5]thiadiazole receptor].

Two new chromophores with carbazole as molecular focal point bearing either one o-pyridine-benzothiadiazole unit or two o-pyridine-benzothiadiazole units at the periphery respectively, named as 2,8-(o-pyridine-benzothiadiazole)-N-ethyl-carbazole (CPTZ1) and 2,8-bis(o-pyridine-benzothiadiazole)-N-ethyl-carbazole (CPTZ2), were synthesized and characterized by IR spectra, 1H NMR spectra and MS. The influence of proton upon one-photon and two-photon fluorescence about these two compounds was discussed. Stern-Volmer equation gives that the S-V constants (k(SV)(1P)) of one-photon fluorescence (1PF) of CPTZ1 and CPTZ2 are 0.04 and 0.10 L mol(-1), respectively; while the k(SV)(2P) of two-photon fluorescence (2PF) of CPTZ1 and CPTZ2 are 0.20 and 0.22 L mol(-1), respectively. Obviously, two-photon (2P) fluorescence detection presented more sensitivity than one-photon (1P) fluorescence response, which exhibits the potential application of two-photon sensor in PH detection.

[Yin-yang penetrating acupuncture with elongated needle for spastic limb dysfunction after stroke: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect between yin-yang penetrating acupuncture with elongated needle and routine acupuncture for spastic limb dysfunction after stroke. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each group. Both groups received basic treatment, yin-yang penetrating acupuncture with elongated needle was applied from Yanglingquan (GB 34) to Xuanzhong (GB 39), Quchi (LI 11) to Wenliu (LI 7), Huantiao (GB 30) to Fengshi (GB 31), Jianyu (LI 15) to Quchi (LI 11), etc. on the affected side in the observation group; routine acupuncture was applied at Neiguan (PC 6), Shuigou (GV 26), Sanyinjiao (SP 6), Jiquan (HT 1), Chize (LU 5), Weizhong (BL 40), Jianyu (LI 15), etc. on the affected side in the control group. Once a day, 5 times a week, 2 weeks as a course, 2 courses were required in the two groups. Before and after treatment，the modified Ashworth scale (MAS) grade, Fugl-Meyer assessment scale (FMA) score, activity of daily living scale (ADL) (Barthel index) score were observed, and the clinical effect was evaluated in the two groups. RESULTS: Compared before treatment, the MAS grade after treatment was improved in the two groups (P<0.05), that in the observation group was superior to the control group (P<0.05). Compared before treatment, the FMA and ADL scores after treatment were increased in the two groups (P<0.05), the changes in the observation group were larger than the control group (P<0.05). The total effective rate in the observation group was 80.0% (24/30), which was superior to 70.0% (21/30) in the control group (P<0.05). CONCLUSION: Yin-yang penetrating acupuncture with elongated needle could improve muscle tension, spasm grade and motor function in patients with spastic limb dysfunction after stroke, enhance the activity of daily living, its clinical effect is superior to routine acupuncture.

Biomechanical researches on tissue engineering bone constructed by deproteinated bone.

OBJECTIVE: To study biomechanical changes of newly formed bones 24 weeks after repairing large defects of long bones of goats using heterogeneous deproteinated bone (DPB) prepared by modified methods as an engineering scaffold. METHODS: According to a fully randomized design, 18 goats were evenly divided into three groups: normal bone control group (Group A), autologous bone group (Group B) and experimental group (Group C). Each goat in Groups B and C were subjected to the periosteum and bone defect at middle-lower part of the right tibia (20% of the whole tibia in length), followed by autologous bone or DPB plus autologous MSCs + rhBMP2 implantation, respectively and semi-ring slot fixation; while goats in Group A did not perform osteotomy. At 24 weeks after surgery, biomechanical tests were carried out on the tibias. RESULTS: At 24 weeks after surgery, the results of anti-compression test on tibias in three groups were recorded by a functional recorder presented as linear pressure-deformation curve. The shapes of the curves and their change tendency were similar among three groups. The ultimate pressure values were 10.74 MPa+/-1.23 MPa, 10.11 MPa+/-1.35 MPa and 10.22 MPa+/-1.32 MPa and fracture compression rates were 26.82%+/-0.87%, 27.17%+/-0.75% and 28.22%+/-1.12% in Groups A, B and C, respectively. Comparisons of anti-compression ultimate pressures and fracture compression rates among three groups demonstrated no significant difference (P(AB) equal to 0.415, P(BC) equal to 0.494). Three-point anti-bend test on tibias was recorded as load-deformation curves, and the shapes of the curves and their change tendency were similar among three groups. The ultimate pressure values of the anti-bend test were 481.52 N+/-12.45 N, 478.34 N+/-14.68 N and 475.62 N+/-13.41 N and the fracture bend rates were 2.62 mm+/-0.12 mm, 2.61 mm+/-0.15 mm and 2.81 mm+/-0.13 mm in Groups A, B and C, respectively. There was no significant difference between groups (P(AB) equal to 0.7, P(BC) equal to 0.448). The ultimate anti-torsion torque values were 6.55 Nm+/-0.25 Nm, 6.34 Nm+/-0.18 Nm and 6.42 Nm+/-0.21 Nm and fracture torsion rates were 29.51 degree+/-1.64degree, 28.88 degree+/-1.46 degree and 28.81 degree+/-1.33 degree in Groups A, B and C, respectively. There was no significant difference between groups (P(AB) equal to 0.123, P(BC) equal to 0.346). CONCLUSIONS: The biomechanical characteristics of newly formed bones from heterogeneous DPB for repairing large segmental long bone defect are comparable to those of normal bones and autologous bones. DPB has the potential for clinical usage as bone graft material.

[Characteristics of Haze Pollution Episodes During Autumn and Winter in 2018 in Shijiazhuang].

The mass concentration and chemical composition of fine particles were continuously observed on-line from October 31 to December 3, 2018 at Hebei Key Laboratory of Haze Pollution Prevention and Control in Shijiazhuang. The characteristics of haze pollution in autumn and winter in Shijiazhuang were analyzed. The results showed that during the observation period, four haze pollution episodes occurred with PM2.5 as the primary pollutant, and the maximum daily concentration was 154, 228, 379, and 223 µg·m-3, respectively, reaching a heavy pollution level or above. The main components of PM2.5were water-soluble inorganic ions (WSⅡ) and carbon-containing aerosols, accounting for (60.7±15.6)% and (21.6±9.7)% of PM2.5 mass concentration, respectively. Compared with clean days, the mass concentration of WSⅡ and carbon aerosol during haze pollution increased by 4.4 times and 3.1 times, respectively, which was the main cause of haze pollution. NO3-, SO42-, and NH4+(SNA) were the main components of WSⅡ, accounting for (91.5±17.3)% of the total WSⅡ concentration, of which NO3- took up the highest proportion. The explosive growth of SNA during haze pollution was the main reason for the extremely high PM2.5concentration. Under non-high humidity conditions, the formation rates of unit mass substrates (NO3-, SO42-) were not significantly different, but the transformation of SO42- was significantly promoted after the liquid phase oxidation of SO2 was triggered under high humidity conditions. The atmosphere in Shijiazhuang is rich in NH3, and the molar ratio of n(NH4+) to n(NO3-+2×SO42-) in PM2.5 was greater than 1. The presence of a large amount of NH3 could promote the transformation of NO3- and SO42- and aggravate pollution. During the haze pollution period, the accumulation of primary pollutants from coal and motor vehicles was the main reason for the increase in carbon-containing aerosol. Compared with clean days, the formation of SOC was inhibited. Before the beginning of the warm season, the mobile form was the main pollution source of PM2.5, contributing 30.8% and 39.8% of PM2.5 mass concentration. With the increase of coal combustion emissions, the contribution of coal-fired sources gradually increased to 25.5%, becoming the primary pollution source.

Multifunctionalized polyethersulfone membranes with networked submicrogels to improve antifouling property, antibacterial adhesion and blood compatibility.

Intensive efforts have been employed in modifying biomedical membranes. Among them, blending is recognized as a simple method. However, the conventional blending materials commonly lead to an insufficient modification, which is mainly caused by the poor miscibility between the blending materials and the matrixes, the elution of the hydrophilic materials from the matrixes during the use and storage, and the insufficient surface enrichment of the blending materials. Aiming to solve the abovementioned disadvantages, we developed novel polyethersulfone/poly(acrylic acid-co-N-vinyl-2-pyrrolidone) networked submicrogels (PES/P(AA-VP) NSs), which were blended with PES to enhance the antifouling properties, antibacterial adhesion and haemocompatible properties of PES membranes. As results, the PES/P(AA-VP) NSs showed good miscibility with the PES matrix, and hydrophilic submicrogels would enrich onto the membrane surface during the phase inversion process due to the surface segregation. The entanglement between the PES matrix and the networked submicrogels would effectively limit the elution of the submicrogels. In conclusion, the modified PES membranes prepared by blending with the PES/P(AA-VP) NSs might draw great attention for the application in haemodialysis fields.

Unsatisfying antiviral therapeutic effect in patients with mother-to-child transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study.

BACKGROUND: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. METHODS: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. RESULTS: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. CONCLUSION: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. TRIAL REGISTRATION: NCT01962155; https://clinicaltrials.gov.

Engineering sodium alginate-based cross-linked beads with high removal ability of toxic metal ions and cationic dyes.

Sodium alginate (SA) beads with ultrahigh adsorption capacity were prepared via hydrogen bonds between SA and 2-acrylamido-2-methylpropa-1-propanesulfonic acid (AMPS), and the AMPS was then post-cross-linked to manufacture SA/PAMPS beads. The equilibrium adsorption capacities of methylene blue (MB) and Pb2+ for the SA/PAMPS10 beads were 2977 and 2042 mg/g, respectively. Although the SA beads exhibited higher equilibrium adsorption capacities of MB and Pb2+ than those of the SA/PAMPS10 beads, the SA/PAMPS10 beads had better mechanical property and higher stability. The pseudo-second-order kinetic model and the Langmuir isotherm described the adsorption processes of the SA/PAMPS10 beads for MB well. In addition, the SA/PAMPS10 beads could be reused with stable adsorption capacity for at least three cycles. The beads also had excellent performances on absorbing methylene violet and other heavy metal ions (Cu2+, Cd2+ and Ni2+). Therefore, the SA-based beads with high adsorption capacity might be good candidates for industrial pollutant treatments.

Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats.

BACKGROUND: The hypothalamus plays a central role in the regulation of metabolism by sensing metabolic demands and releasing regulatory neurotransmitters. This study investigated the response of the hypothalamus to glucose ingestion in rats by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and immunohistochemical techniques to determine the role of the hypothalamus in glyco-regulation during disturbances in carbohydrate metabolism. METHODS: The signal intensity of the hypothalamus was monitored by fMRI for 60 minutes after oral glucose intake in 48 healthy rats (age 14 months), which included 24 normal weight rats (weighing (365 +/- 76.5) g) and 24 overweight rats (weighing (714 +/- 83.5) g). Then, 12 rats (6 normal, 6 overweight) underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for fMRI with water intake was the same as for glucose ingestion. fMRI data was processed using time cluster analysis and intensity averaging method. After fMRI, the expression of neuropeptide Y (NPY) and 5-hydroxytryptamine (5-HT) in the hypothalamus of all rats was determined by immunohistochemistry. Positive cells for NPY or 5-HT were counted. RESULTS: There was a transient, but significant, decrease in fMRI signal intensity in all rats (mean (3.12 +/- 0.78)%) in the hypothalamus within 19.5 - 25.5 minutes of oral glucose ingestion. In overweight rats, the decrease in signal intensity in response to the glucose ingestion was more markedly attenuated than that observed in normal weight rats ((2.2 +/- 1.5)% vs (4.2 +/- 0.7)% inhibition, t = 2.12, P < 0.05). There was no significant response in the hypothalamus after oral water ingestion. The percentage of NPY positive cells in obese rats were slightly lower than those in control group (21% vs 23%, t = 0.71, P > 0.05); but there was no significant difference between the two groups; the percentage of 5-HT positive cells in obese rats were significantly lower than those in the control group (22% vs 31%, t = 3.25, P < 0.01). CONCLUSIONS: There is a transient, but significant, decrease in BOLD signal intensity in the hypothalamus following glucose ingestion, which is similar to that observed in humans. The response of the hypothalamus to glucose ingestion was different in overweight and normal weight rats. The percentage of NPY positive cells in obese rats were lower than those in the control group, although this difference was not statistically significant. The percentage of 5-HT positive cells in obese rats was significantly lower than those in the control group.