Specific lineage transition of tumor-associated macrophages elicits immune evasion of ascitic tumor cells in gastric cancer with peritoneal metastasis.

BACKGROUND: Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs). METHODS: Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs. RESULTS: Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsinhigh (CTShigh) to complement 1qhigh (C1Qhigh) TAM. CTShigh TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Qhigh TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Qhigh TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway. CONCLUSIONS: For the first time, we identified an immunosuppressive macrophage transition from CTShigh to C1Qhigh TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.

Curcumin analogues exert potent inhibition on human and rat gonadal 3ß-hydroxysteroid dehydrogenases as potential therapeutic agents: structure-activity relationship and in silico docking.

Curcuminoids are functional food additives, and the effect on gonadal hormone biosynthesis remains unclear. Gonads contain 3ß-hydroxysteroid dehydrogenase isoforms, h3ß-HSD2 (humans) and r3ß-HSD1 (rats), which catalyse pregnenolone into progesterone. The potency and mechanisms of curcuminoids to inhibit 3ß-HSD activity were explored. The inhibitory potency was bisdemethoxycurcumin (IC50, 1.68 µM) >demethoxycurcumin (3.27 µM) > curcumin (13.87 µM) > tetrahydrocurcumin (109.0 µM) > dihydrocurcumin and octahydrocurcumin on KGN cell h3ß-HSD2, while that was bisdemethoxycurcumin (1.22 µM) >demethoxycurcumin (2.18 µM) > curcumin (4.12 µM) > tetrahydrocurcumin (102.61 µM) > dihydrocurcumin and octahydrocurcumin on testicular r3ß-HSD1. All curcuminoids inhibited progesterone secretion by KGN cells under basal and forskolin-stimulated conditions at >10 µM. Docking analysis showed that curcuminoids bind steroid-active site with mixed or competitive mode. In conclusion, curcuminoids inhibit gonadal 3ß-HSD activity and de-methoxylation of curcumin increases inhibitory potency and metabolism of curcumin by saturation of carbon chain losses inhibitory potency.

Direct inhibition of bisphenols on human and rat 11ß-hydroxysteroid dehydrogenase 2: Structure-activity relationship and docking analysis.

Bisphenols (BPs) as endocrine-disrupting compounds have drawn attention to their health hazards. Whether a BP interferes with glucocorticoid metabolism remains unclear. 11ß-Hydroxysteroid dehydrogenase 2 (11ß-HSD2) is a key glucocorticoid-metabolizing enzyme that controls fetal glucocorticoid levels across the placental barrier and mineralocorticoid receptor specificity in the kidney. In this study, 11 BPs were tested to inhibit human placental and rat renal 11ß-HSD2 and were analyzed for inhibitory potency, mode action, and docking parameters. BPs had inhibitory potency against human 11ß-HSD2: BPFL>BPAP>BPZ>BPB>BPC>BPAF>BPA>TDP and the IC10 values were 0.21, 0.55, 1.04, 2.04, 2.43, 2.57, 14.43, and 22.18 µM, respectively. All BPs are mixed inhibitors except BPAP, which is a competitive inhibitor for human 11ß-HSD2. Some BPs also inhibited rat renal 11ß-HSD2, with BPB (IC50, 27.74 ± 0.95) > BPZ (42.14 ± 0.59) > BPAF (54.87 ± 1.73) > BPA (77.32 ± 1.20) > other BPs (about 100 µM). Docking analysis showed that all BPs bound to the steroid-binding site, interacting with the catalytic residue Tyr232 of both enzymes and the most potent human 11ß-HSD2 inhibitor BPFL acts possibly due to its large fluorene ring that has hydrophobic interaction with residues Glu172 and Val270 and π-stacking interaction with catalytic residue Tyr232. The increase in the size of substituted alkanes and halogenated groups in the methane moiety of the bridge of BPs increases its inhibitory potency. Regressions of the lowest binding energy with inhibition constant indicated that there was an inverse regression. These results indicated that BPs significantly inhibited human and rat 11ß-HSD2 activity and that there were species-dependent differences.

Blood retinol and retinol-binding protein concentrations are associated with diabetes: a systematic review and meta-analysis of observational studies.

PURPOSE: The associations between blood retinol, retinol-binding protein (RBP) concentrations and diabetes mellitus were inconsistent in literature. The objective is to investigate these associations by a systematic review and meta-analysis and provide basis for clinical intervention. METHODS: PubMed, Web of science, and Cochrane databases were searched from the beginning to July 1, 2021. A total of 13 studies on retinol and 31 studies on RBP are included in the current meta-analysis. RESULTS: The blood retinol concentration was significantly lower in the type I diabetes mellitus (T1DM) [standardized mean difference (SMD) (95% CI): - 0.59 (- 0.81, - 0.37), P < 0.01] and gestational diabetes mellitus (GDM) patients [SMD (95% CI): - 0.54 (- 0.87, - 0.20), P < 0.01] than in the controls. However, the difference was not significant between the type II diabetes mellitus (T2DM) patients and the controls. The RBP concentration was significantly higher in the diabetic patients than in the controls [SMD (95% CI): 0.24 (0.12, 0.35), P < 0.01]. Particularly, the RBP concentration was significantly higher in the T2DM and GDM patients. CONCLUSION: The blood retinol concentration was negatively associated with T1DM and GDM, while the blood RBP concentration was positively associated with T2DM and GDM. Future work should use a more sensitive retinol measurement method like retinol isotope dilution method to confirm whether blood retinol concentration differs between the diabetes patients and the controls.

Enzyme-catalyzed biodegradation of penicillin fermentation residues by ß-lactamase OtLac from Ochrobactrum tritici.

BACKGROUND: Biodegradation of antibiotics is a promising method for the large-scale removal of antibiotic residues in the environment. However, the enzyme that is involved in the biodegradation process is the key information to be revealed. RESULTS: In this study, the beta-lactamase from Ochrobactrum tritici that mediates the biodegradation of penicillin V was identified and characterized. When searching the proteins of Ochrobactrum tritici, the ß-lactamase (OtLac) was identified. OtLac consists of 347 amino acids, and predicted isoelectric point is 7.0. It is a class C ß-lactamase according to BLAST analysis. The coding gene of OtLac was amplified from the genomic DNA of Ochrobactrum tritici. The OtLac was overexpressed in E. coli BL21 (DE3) and purified with Ni2+ column affinity chromatography. The biodegradation ability of penicillin V by OtLac was identified in an in vitro study and analyzed by HPLC. The optimal temperature for OtLac is 32 â„ƒ and the optimal pH is 7.0. Steady-state kinetics showed that OtLac was highly active against penicillin V with a Km value of 17.86 µM and a kcat value of 25.28 s-1 respectively. CONCLUSIONS: OtLac demonstrated biodegradation activity towards penicillin V potassium, indicating that OtLac is expected to degrade penicillin V in the future.

Effects of resistant starch supplementation on oxidative stress and inflammation biomarkers: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Animal experiments showed that resistant starch (RS) had an antioxidant and antiinflammatory effect. However, clinical studies showed both insignificant and significant effects of RS on inflammation and oxidative stress. The purpose of this work is to conduct a systematic review and meta-analysis of previous randomized controlled trials (RCTs) to investigate these effects. METHODS AND STUDY DESIGN: A systematic literature search was conducted on Web of Science, Scopus, PubMed and Cochrane electronic databases, which included studies from the earliest date of the database to September 2021. Key inclusion criteria were: RCTs; reporting at least one inflammatory or oxidative stress biomarker as endpoint; more than seven day intervention. Key exclusion criteria were: using a mixture of RS and other functional food ingredients as intervention substance; inappropriate controls. RESULTS: A total of 16 RCTs including 706 subjects were included. RS supplementation significantly improved total antioxidant capacity [standard mean difference (SMD) (95% CI): 2.64 (0.34, 4.94), p=0.03], and significantly reduced blood malondialdehyde concentration [SMD (95% CI): -0.55 (- 0.94, -0.17), p=0.01]. RS supplementation significantly reduced blood C-reactive protein concentration in type 2 diabetes mellitus (T2DM) patients [SMD (95% CI): -0.35 (-0.65, -0.05), p=0.02]. RS consumption significantly reduced blood interlukin-6 and tumor necrosis factor- concentration if removing one distinct trial. CONCLUSIONS: RS supplementation may significantly reduce a few oxidative-stress and inflammation biomarkers such as malondialdehyde and C-reactive protein, particularly in T2DM patients. Future work should investigate the optimal dosage of RS supplementation for modulating oxidative stress and inflammation biomarkers related to T2DM.

Simultaneous production of propionic acid and vitamin B12 from corn stalk hydrolysates by Propionibacterium freudenreichii in an expanded bed adsorption bioreactor.

Vitamin B12 and propionic acid that were simultaneous produced by Propionibacterium freudenreichii are both favorable chemicals widely used in food preservatives, medicine, and nutrition. While the carbon source and propionic acid accumulation reflected fermentation efficiency. In this study, using corn stalk as a carbon source and fed-batch fermentation process in an expanded bed adsorption bioreactor was studied for efficient and economic biosynthesis of acid vitamin B12 and propionic. With liquid hot water pretreated corn stalk hydrolysates as carbon source, 28.65 mg L-1 of vitamin B12 and 17.05 g L-1 of propionic acid were attained at 168 h in batch fermentation. In order to optimize the fermentation outcomes, fed-batch fermentation was performed with hydrolyzed corn stalk in expanded bed adsorption bioreactor (EBAB), giving 47.6 mg L-1 vitamin B12 and 91.4 g L-1 of propionic acid at 258 h, which correspond to product yields of 0.37 mg g-1 and 0.75 g g-1, respectively. The present study provided a promising strategy for economically sustainable production of vitamin B12 and propionic acid by P. freudenreichii fermentation using biomass cornstalk as carbon source and expanded bed adsorption bioreactor.

Novel one-, two-, and three-dimensional selenidostannates templated by iron(II) complex cation.

The novel iron selenidostannates [Fe(bipy)3]Sn4Se9·2H2O (1) and [Fe(bipy)3]2[Sn3Se7]2·bipy·2H2O (2) (bipy = bipyridine) were prepared by the reactions of Sn, Se, FeCl2·4H2O, bipy, and dien with/without KSCN under hydrothermal conditions (dien = diethylenetriamine). In 1, four SnSe5 units condense via edge sharing to form the novel 3-D framework selenidostannate (∞)³[Sn4Se9²â»] containing an interpenetrating channel system. The [Fe(bipy)3]²âº cations are accommodated in the different channels according to the conformation of the [Fe(bipy)3]²âº cation. In 2, three SnSe5 units share edges to form a 2-D (∞)²[Sn3Se7²â»] layered anion, while two SnSe5 units and one SnSe4 unit are connected via edge sharing, forming a 1-D (∞)¹[Sn3Se7²â»] chainlike anion. The (∞)¹[Sn3Se7²â»], [Fe(bipy)3]²âº, bipy, and H2O species are embedded between the (∞)²[Sn3Se7²â»] layers. 2 is the first example of a selenidostannate constructed by both (∞)²[Sn3Se7²â»]and (∞)¹[Sn3Se7²â»] anions. The coexistence of 1-D (∞)¹[Sn3Se7²â»] and 2-D (∞)²[Sn3Se7²â»] anions in 2 might support the possible reaction mechanism that the (∞)²[Sn3Se7²â»] anions are formed by condensation of the (∞)¹[Sn3Se7²â»] chains. 1 and 2 exhibit band gaps at 1.43 and 2.01 eV, respectively.

Tracking circulating PD-L1-positive cells to monitor the outcome of patients with gastric cancer receiving anti-HER2 plus anti-PD-1 therapy.

Dual blockade of HER2 and PD-1/PD-L1 is the most promising regimen for HER2-positive patients with gastric cancer (GC); PD-L1 combined positive score, rather than HER2 status, indicates potential benefit. Circulating tumor cells (CTCs) and circulating endothelial cells (CECs) derived from the tumor microenvironment provide platforms for the dynamic evaluation of PD-L1 expression. Whether PD-L1 positive CTCs/CECs (PD-L1+CTCs/CECs) can serve as biomarkers for evaluating the efficacy of combination therapy remains unknown. Therefore, this study investigated PD-L1 expression and heterogeneous karyotypic features of CTCs/CECs and their involvement in the clinical response to treatment in 72 patients with advanced GC by applying a pre-established surface molecule-independent subtraction enrichment (SE)-iFISH strategy. In the captured PD-L1 positive cells, there were 42.80% and 57.20% of CTCs and CECs, respectively. PD-L1+ CTCs were pre-therapeutically detected in 0% (0/11) of HER2-negative patients and 14.75% (9/61) of HER2-positive patients. The presence of baseline PD-L1+CTCs was relevant to inferior prognosis (mPFS: 14.40 months vs 5.00 months, P = 0.065); post-treatment PD-L1+ CECs were associated with longer irPFS (immunotherapeutic-related PFS) (mPFS: 15.57 months vs 6.73 months, P = 0.053). Further dynamic karyotype-based profiling of PD-L1+ CTCs/CECs indicated that multiploidy and triploidy were the dominant subtypes of baseline PD-L1+ CTCs, and that triploidy was specifically associated with therapeutic resistance. Intratherapeutically detected multiploid PD-L1+ CECs demonstrated a superior clinical response; triploidy and tetraploidy contributed to acquired resistance. The karyotypic features of PD-L1+CTCs/CECs should be dynamically profiled in patients with GC treated with anti-HER2 plus anti-PD-1 therapy. Triploid-PD-L1+ CTCs and multiploid-PD-L1+ CECs are potential indicators of therapeutic response.

Boosting photothermal-assisted photocatalytic H2 production over black g-C3N4 nanosheet photocatalyst via incorporation with carbon dots.

Although photocatalytic H2 production based on semiconductor materials has a wide potential application, it still facing challenges such as slow reaction kinetics or complex synthesis processes. To meet these challenges, the carbon dots loaded black g-C3N4 (CN-B-CDs) was synthesized by simple calcination method to achieve efficient photothermal-assisted photocatalytic H2 production. Photothermal imaging experiments confirmed the photothermal effect of CN-B and CDs as dual heat sources to increase the temperature of the composite system, thus improving the effective separation of photo-generated charges. In addition, multiple photocatalytic H2 production tests exhibited that CN-B-CDs photocatalysts not only have strong stability but also can accommodate a variety of complex water bodies, which displayed the potential for industrial application. This study combined the photothermal effect and the mechanism by which the CDs promote the charge transfer to design a new photocatalytic H2 production system and provided a new scheme for achieving efficient photothermal-assisted photocatalytic H2 production using carbon-based materials.

Vitamin D receptor gene polymorphisms, bioavailable 25-hydroxyvitamin D, and hepatocellular carcinoma survival.

BACKGROUND: Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. METHODS: We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was only significant in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS. CONCLUSIONS: Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

Multiple electromagnet synergistic control enabled fast and automatic biosensing of Salmonella in a sealed microfluidic chip.

Point-of-care testing of pathogens is vital for prevention of food poisoning. Herein, a colorimetric biosensor was elaborately developed to rapidly and automatically detect Salmonella in a sealed microfluidic chip with one central chamber for housing immunomagnetic nanoparticles (IMNPs), bacterial sample and immune manganese dioxide nanoclusters (IMONCs), four functional chambers for housing absorbent pad, deionized water and H2O2-TMB substrate, and four symmetric peripheral chambers for achieving fluidic control. Four electromagnets were placed under peripheral chambers and synergistically controlled to manipulate their respective iron cylinders at the top of these chambers for deforming these chambers, resulting in precise fluidic control with designated flowrate, volume, direction and time. First, the electromagnets were automatically controlled to mix IMNPs, target bacteria and IMONCs, resulting in the formation of IMNP-bacteria-IMONC conjugates. Then, these conjugates were magnetically separated by a central electromagnet and the supernatant was directionally transferred to the absorbent pad. After these conjugates were washed by deionized water, the H2O2-TMB substrate was directionally transferred to resuspend the conjugates and catalyzed by the IMONCs with peroxidase-mimic activity. Finally, the catalysate was directionally transferred back to its initial chamber, and its color was analyzed by the smartphone APP to determinate bacterial concentration. This biosensor could detect Salmonella quantitatively and automatically in 30 min with a low detection limit of 101 CFU/mL. More importantly, the whole bacterial detection procedure from bacterial separation to result analysis was achieved on a sealed microfluidic chip through multiple electromagnet synergistic control, and this biosensor has great potential for point-of-care testing of pathogens without cross contaminations.

Platelet-rich plasma in the pathologic processes of tendinopathy: a review of basic science studies.

Tendinopathy is a medical condition that includes a spectrum of inflammatory and degenerative tendon changes caused by traumatic or overuse injuries. The pathological mechanism of tendinopathy has not been well defined, and no ideal treatment is currently available. Platelet-rich plasma (PRP) is an autologous whole blood derivative containing a variety of cytokines and other protein components. Various basic studies have found that PRP has the therapeutic potential to promote cell proliferation and differentiation, regulate angiogenesis, increase extracellular matrix synthesis, and modulate inflammation in degenerative tendons. Therefore, PRP has been widely used as a promising therapeutic agent for tendinopathy. However, controversies exist over the optimal treatment regimen and efficacy of PRP for tendinopathy. This review focuses on the specific molecular and cellular mechanisms by which PRP manipulates tendon healing to better understand how PRP affects tendinopathy and explore the reason for the differences in clinical trial outcomes. This article has also pointed out the future direction of basic research and clinical application of PRP in the treatment of tendinopathy, which will play a guiding role in the design of PRP treatment protocols for tendinopathy.

[Research progress on the role and clinical application of Siglecs in tumor immunity].

Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.

Plasmonic coupling-boosted photothermal nanoreactor for efficient solar light-driven photocatalytic water splitting.

Photothermal nanoreactor with rapid charge transfer and improved spectral utilization is a key point in photocatalysis research. Herein, silver sulfide quantum dots (Ag2S QDs) were coating on the surface of porous graphitic carbon nitride nano vesicles (PCNNVs) to form Ag2S/PCNNVs nanoreactors by a simple calcination method for obtaining efficient photothermal-assisted photocatalytic hydrogen (H2) evolution under simulated/real sunlight irradiation. In particularly, the as-prepared optimal 3% Ag2S/PCNNVs sample exhibited the H2 production rate of 34.8 mmol h-1 g-1, which was 3.5 times higher than that of bare PCNNVs. The enhancement of photothermal-assisted activity over the Ag2S/PCNNVs composite system is mainly attributed to the coupling of the photothermal conversion performance of Ag2S QDs and the thermal insulation performance of PCNNVs based on the plasmonic coupling-boosted photothermal nanoreactor. This study presents a promising strategy for the development of high-efficient photothermal-assisted photocatalysts.

Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global public health problem. Chronic hepatitis B (CHB) patients can be divided into treatment indication and non-treatment indication individuals according to alanine transaminase (ALT), HBV DNA, serum hepatitis B e antigen status, disease status [liver cirrhosis, hepatocellular carcinoma (HCC), or liver failure], liver necroinflammation or fibrosis, patients' age, and family history of HCC or cirrhosis. For example, normal ALT patients in 'immune-tolerant' phase with HBV DNA higher than 107 or 2 × 107 IU/mL, and those in 'inactive-carrier' phase with HBV DNA lower than 2 × 103 IU/mL do not require antiviral therapy. However, is it reasonable to set the defined values of HBV DNA as the fundamental basis to estimate the disease state and to determine whether to start treatment? In fact, we should pay more attention to those who do not match the treatment indications (gray-zone patients both in the indeterminate phase and in the 'inactive-carrier' phase). AIM: To analyze the correlation of HBV DNA level and liver histopathological severity, and to explore the significance of HBV DNA for CHB with normal ALT. METHODS: From January 2017 to December 2021, a retrospective cross-sectional set of 1299 patients with chronic HBV infection (HBV DNA > 30 IU/mL) who underwent liver biopsy from four hospitals, including 634 with ALT less than 40 U/L. None of the patients had received anti-HBV treatment. The degrees of liver necroinflammatory activity and liver fibrosis were evaluated according to the Metavir system. On the basis of the HBV DNA level, patients were divided into two groups: Low/moderate replication group, HBV DNA ≤ 107 IU/mL [7.00 Log IU/mL, the European Association for the Study of the Liver (EASL) guidelines] or ≤ 2 × 107 IU/mL [7.30 Log IU/mL, the Chinese Medical Association (CMA) guidelines]; high replication group, HBV DNA > 107 IU/mL or > 2 × 107 IU/mL. Relevant factors (demographic characteristics, laboratory parameters and noninvasive models) for liver histopathological severity were analyzed by univariate analysis, logistics analysis and propensity score-matched analysis. RESULTS: At entry, there were 21.45%, 24.29%, and 30.28% of the patients had liver histopathological severities with ≥ A2, ≥ F2, and ≥ A2 or/and ≥ F2, respectively. HBV DNA level (negative correlation) and noninvasive model liver fibrosis 5 value (positive correlation) were independent risk factors for liver histopathological severities (liver necroinflammation, liver fibrosis, and treatment indication). The AUROCs of the prediction probabilities (PRE_) of the models mentioned above (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.814 (95%CI: 0.770-0.859), 0.824 (95%CI: 0.785-0.863), and 0.799 (95%CI: 0.760-0.838), respectively. HBV DNA level (negative correlation) was still an independent risk factor when diagnostic models were excluded, the P values (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.011, 0.000, and 0.000, respectively. For the propensity score-matched pairs, whether based on EASL guidelines or CMA guidelines, the group with significant liver histology damage (≥ A2 or/and ≥ F2) showed much lower HBV DNA level than the group with non- significant liver histology damage (< A2 and < F2). Patients in the moderate replication group (with indeterminate phase) had the most serious liver disease pathologically and hematologically, followed by patients in the low replication group (with 'inactive-carrier' phase) and then the high replication group (with 'immune-tolerant' phase). CONCLUSION: HBV DNA level is a negative risk factor for liver disease progression. The phase definition of CHB may be revised by whether the level of HBV DNA exceeds the detection low limit value. Patients who are in the indeterminate phase or 'inactive carriers' should receive antiviral therapy.

[Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

OBJECTIVE: To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). METHODS: The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. RESULTS: Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P < 0.05). CONCLUSIONS: Monotherapy with icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

Chemodrug-gated mesoporous nanoplatform for new near-infrared light controlled drug release and synergistic chemophotothermal therapy of tumours.

Controlled drug release and synergistic therapies have an important impact on improving therapeutic efficacy in cancer theranostics. Herein, a new near-infrared (NIR) light-controlled multi-functional nanoplatform (GNR@mSiO2-DOX/PFP@PDA) was developed for synergistic chemo-photothermal therapy (PTT) of tumours. In this nano-system, doxorubicin hydrochloride (DOX) and perfluoro-n-pentane (PFP) were loaded into the channels of mesoporous SiO2 simultaneously as a first step. A polydopamine (PDA) layer as the gatekeeper was coated on their surface to reduce premature release of drugs at physiological temperature. Upon 808 nm NIR irradiation, the gold nanorods (GNR) in the core of the nanoplatform show high photothermal conversion efficiency, which not only can provide the heat for PTT, but also can decompose the polymer PDA to allow DOX release from the channels of mesoporous SiO2. Most importantly, the photothermal conversion of GNR can also lead the liquid-gas phase transition of PFP to generate bubbles to accelerate the release of DOX, which can realize the chemotherapy of tumours. The subsequent synergistic chemo-PTT (contributed by the DOX and GNR) shows good anti-cancer activity. This work shows that the NIR-triggered multi-functional nanoplatform is of capital significance for future potential applications in drug delivery and cancer treatment.

Quantitative proteomic analysis reveals the effects of mu opioid agonists on HT22 cells.

Introduction: At present, the mu opioid receptor is the most important neuroaesthetics receptor in anesthesiology research, and the damage that it does to the nervous system is unknown. Methods: We investigated the effects of loperamide, an agonist of the mu opioid receptor, on protein expression in HT22 cells using stable isotope labeling of amino acids in cell culture (SILAC), immobilized metal affinity chromatography (IMAC) enrichment, and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 7,823 proteins were identified. Results and Discussion: Bioinformatic analysis revealed that mu opioid receptor agonism can induce distinct changes in the proteome of HT22 cells. These findings improve our understanding of narcotic drugs.

Associating the blood vitamin A, C, D and E status with tuberculosis: a systematic review and meta-analysis of observational studies.

Vitamins may play an important role in preventing tuberculosis. The purpose of this work is to associate the vitamin A, C, D and E status with tuberculosis through a systematic review and meta-analysis of observational studies. Web of Science, Pubmed and Scopus were searched from the earliest date of the database to May 2021. The standardized mean differences (SMDs) of blood vitamin concentrations and odds ratios (ORs) of vitamin deficiency between the tuberculosis patients and the control subjects were used as the main effect sizes. The effect sizes were pooled by a random-effects model using the Stata software (Version 11). The vitamin A concentration was significantly lower in the tuberculosis group than in the control group [SMD (95% CI): -0.96 (-1.31, -0.61), p < 0.01]. Only two case-control studies reported the vitamin C concentrations in the tuberculosis group versus the control group, and the difference was not significant. The blood vitamin D concentration was significantly lower in the tuberculosis group than in the control group [SMD (95% CI): -0.53 (-0.75, -0.32), p < 0.01]. Consistently, the number of people with vitamin D deficiency was significantly higher in the tuberculosis group [OR (95% CI): 2.29 (1.55, 3.37), p < 0.01]. The vitamin E concentration was significantly lower in the tuberculosis group than in the control group [SMD (95% CI): -0.34 (-0.61, -0.08), p = 0.01]. The current meta-analysis suggested a negative association between the vitamin A, D and E status and tuberculosis, and the association between the vitamin C status and tuberculosis was inconclusive due to the limited studies available.