The prognostic role of albumin levels in lung cancer patients receiving third-line or advanced immunotherapy: a retrospective study.

Background: Immunotherapy functions by leveraging immunoregulation drugs to bolster the immune system's capacity to identify and eliminate cancerous cells. In contrast to radiotherapy and chemotherapy, immunotherapy exhibits diminished side effects, heightened efficacy, and prolonged survival rates. Nevertheless, meticulous exploration into the determinants governing the advantageous effects of immunotherapy among patients who have previously undergone multiple prior therapies has yet to be conducted. Albumin (ALB) as a nutritional indicator has not been thoroughly studied for its prognostic effect on efficacy or survival. This study aims to identify factors that influence treatment outcomes among patients undergoing third-line or later immunological therapies. Methods: A cohort of 250 lung cancer patients undergoing toripalimab or tislelizumab immunotherapy was the focal point of data collection. The determination of the median value facilitated the establishment of a cut-off point, enabling the categorization of continuous variables. After data collection, a series of statistical analyses of various clinical factors at baseline were performed, including nonparametric tests, logistic regression, and Cox proportional risk modeling. The last follow-up was in May 2022. The primary study endpoint was overall survival (OS). Results: A total of 250 patients were enrolled in the study, of which 129 patients received first- or second-line immunotherapy and 121 patients received third-line or subsequent immunotherapy. According to Cox multifactor regression analysis, in patients receiving either first- or second-line therapy, the ALB level exhibited negligible prognostic relevance (P>0.05). However, in patients subjected to immunotherapy beyond the second line, the ALB level manifested significant prognostic importance (P=0.039). Notably, patients demonstrating elevated ALB levels achieved a higher disease control rate (DCR) (70.0% vs. 52.5%, P=0.05) and displayed a tendency towards a heightened objective response rate (ORR) (20.0% vs. 16.4%, P=0.61) in comparison to those with lower ALB levels. Conclusions: Among patients undergoing immunotherapy in the third line or subsequent treatment phases, elevated ALB levels in baseline correlated with DCR and OS. Thus, the pre-immunotherapy ALB level emerges as an autonomous predictor of OS in patients subjected to third- or later line immunotherapy interventions.

Effect of immune checkpoint inhibitors at different treatment time periods on prognosis of patients with extensive-stage small-cell lung cancer.

BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death. RESULTS: One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001). CONCLUSION: First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.

Construction of an Artificial Light-Harvesting System with Photocatalytic Activity Based on Nor-seco-cucurbit[10]uril in Aqueous Solution.

A supramolecular assembly was constructed based on the tetraphenylethylene derivatives (TPEs) and nor-seco-cucurbit[10]uril (ns-Q[10]). Upon introduction of the dye Rhodamine B (RB) into the TPEs@ns-Q[10] assembly, an energy transfer process can occur from the TPEs@ns-Q[10] assembly to RB. Moreover, after the addition of Nile Red (NiR), a two-step sequential energy transfer process from the TPEs@ns-Q[10] assembly to RB and then to NiR can occur. Additionally, the dye Eosin Y (ESY) was introduced into the TPEs@ns-Q[10] assembly and an energy transfer process can take place from the TPEs@ns-Q[10] assembly to ESY. To utilize the harvested energy from the TPEs@ns-Q[10]-RB-NiR and TPEs@ns-Q[10]-ESY system, we applied the TPEs@ns-Q[10] assembly-based light-harvesting systems (LHSs) as a catalyst for the advancement of the photocatalytic dehalogenation reaction in aqueous solution. When promoted with 0.5 mol % catalyst, the reaction yield reached 78 and 68%, demonstrating the promising potential of TPEs@ns-Q[10] assembly-based LHSs in the promotion of the photocatalytic dehalogenation reaction.

Detection of basic amino acids under highly alkaline conditions using a perylene amine-derived probe.

pH plays a crucial part in numerous chemical and physiological processes. In this work, a new perylene diimide derivative that acts as a pH-sensitive dye with Bay Area Carboxylic Acid functionality. The derivative utilizes the outstanding thermal, chemical and photochemical stability found in PDI materials and has remarkable UV-visible absorption and fluorescence emission qualities. Based on these properties, a fluorescent probe (PCA) was synthesised using a perylene tetracarbodiimide (PDI) backbone for the recognition of alkaline pH. In alkaline environments where the pH values are between 10 and 14, the fluorescence intensity significantly decreases, and a blue shift occurs, which is a standard feature of alkaline pH probes. The probe demonstrates exceptional sensing ability within the pH range of 10.00-14.00, with notable stability and reversibility. Encapsulation of the probe in a thin polymer film material enhances the pH sensing capability of the system. New sensor has been developed to detect basic amino acids by utilizing the probes' pH response characteristics. this sensor has also been applied to detect the concentration of arginine.

Two new phenolic amides from Allium chinense.

Objective: To isolate the phenolic amides from the dried bulbs of Allium chinense and investigate their myocardium protective activities. Methods: The chemical constituents were isolated and purified by combining with silica gel column, Sephadex LH-20 column, HPLC and other chromatography techniques. Their structures were elucidated by NMR techniques and mass spectrometry. The isolated compounds were evaluated to determine their protective effect for myocardium cells in vitro. Results: Two new phenolic amides, namely, alichinemide I (1) and alichinemide II (2), and six konwn amides were isolated from the dried bulbs of A. chinense. The structures of compounds 3-8 were identified as 3-indolcarbaldehyde (3), 1-(2-aminophenyl)urea (4), 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid (5), N-trans-feruloyltyramine (6), N-trans-p-coumaroyltyramine (7), and N-(3,4-dimethoxyphenethyl) acetamide (8). Compound 3 (50 µmol/L) showed significant inhibitory effect on the damage of H9c2 myocardial cells induced by H2O2in vitro. Conclusion: Compounds 1 and 2 were new phenolic amides. Compound 3 could be one of the potential myocardium protective constituents of A. chinense.

Discovery of Dimethyl Shikonin Oxime 5a, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Type 2 Diabetes Mellitus.

Bombesin receptor subtype-3 (BB3, BRS-3) is an orphan Gαq protein-coupled receptor. The characterization of novel synthetic ligands for BB3 is an alternative and attractive strategy to study its diverse physiological functions. Here, we uncovered the intimate pairing of DMAKO-00 and its derivatives with BB3. Dimethyl shikonin oxime 5a (DSO-5a) was identified as the most potent agonist for BB3 (pEC50 = 8.422 in IP-1 accumulation), which was 898-fold more potent than DMAKO-00. Importantly, without brain penetration, DSO-5a improved glucose tolerance in C57BL/6 mice through BB3 and ameliorated glucose homeostasis in diabetic db/db mice. We further revealed that DSO-5a upregulated PPAR-gamma activity via BB3 through a quantitative proteomics approach. Collectively, our study demonstrated that DSO-5a, a representative compound of DMAKO-00 derivatives, is a potent, selective, and low-brain-penetrating agonist for BB3, and BB3 is a promising treatment target for type 2 diabetes mellitus.

A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier.

Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.

Discovery of oridonin as a novel agonist for BRS-3.

BACKGROUND: Bombesin Receptor Subtype-3 (BRS-3, Bombesin-like receptor, BB3) is an orphan G-protein coupled receptor (GPCR). Recent studies have shown that BRS-3 played a vital role in glucose regulation, insulin secretion, and energy homeostasis. Therefore, discovering more novel exogenous ligands with diverse structures for BRS-3 will be of great importance for target validation and drug development. PURPOSE: In this study, we aim to discover new agonists of BRS-3 from our natural compound libraries, providing a new probe to study the function of BRS-3. STUDY DESIGN: Multiple cell-based assays and in vivo experiments were performed to identify the new ligand. METHODS: BRS-3 overexpression cells were coupled with FLIPR assay, homogeneous time-resolved fluorescence (HTRF) IP-ONE assay, dynamic mass redistribution (DMR) assay, ß-arrestin2 recruitment assay, and western blot to determine receptor activation and downstream signaling events. To further validate the target of BRS-3, a series of in vitro and in vivo experiences were conducted, including glucose uptake, glucose transporter type 4 (GLUT4) transportation in C2C12, and oral glucose tolerance test (OGTT) in mice. RESULTS: We discovered and identified oridonin as a novel small molecule agonist of BRS-3, with a moderate affinity (EC50 of 2.236 × 10-7 M in calcium mobilization assay), specificity, and subtype selectivity. Further in vitro and in vivo tests demonstrated that oridonin exerted beneficial effects in glucose homeostasis through activating BRS-3. CONCLUSIONS: Oridonin, as the discovered new ligand of BRS-3, provides a valuable tool compound to investigate BRS-3's function, especially for target validation in type 2 diabetes and obesity. Oridonin is promising as a lead compound in the treatment of metabolic disorders. Compared to the known agonists of BRS-3, we can take advantage of the multiple reported pharmacological activities of ODN as a natural product and assess whether these pharmacological activities are regulated by BRS-3. This may facilitate the discovery of novel functions of BRS-3.

Oxymatrine attenuates TNBS-induced colinutis in rats through TLR9/Myd88/NF-κB signal pathway.

Objective: Due to its well-known anti-inflammatory property, oxymatrine (OMT) has received more attention on the aspect of treating ulcerative colitis. Although efforts have been undertaken to understand the therapeutic mechanism of OMT on ulcerative colitis (UC), the remedial principle is still ambiguous. Numerous studies have shown that TLR9/Myd88/NF-κB signal pathway played a key role in the pathogenesis of UC. Moreover, TLR9/Myd88/NF-κB signal pathway is a part of the most important pathways for regulating the immune response.Methods: We explored the influence of OMT with different dosages on UC by establishing a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Moreover, the participation of TLR9/Myd88/NF-κB signal pathway and whether OMT protects against UC though targeting this pathway are further studied.Results: Our data revealed that OMT could significantly relieve the symptom of TNBS-induced colitis in rats by reactivating the tight junction protein and, more important, by inhibiting the activation of TLR9/Myd88/NF-κB pathway and protein expression levels of its downstream inflammatory factors.Conclusion: OMT could relieve colitis in rat models by impacting tight junction proteins' TLR9/Myd88/NF-κB signal pathways and activity.

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions.

A novel hemicucurbituril-based macrocycle, alternately consisting of amidobenzene and 2-imidazolidione moieties was designed and synthesized. Based on the fragment coupling strategy, nitrobenzene-containing hemicucurbituril was firstly prepared facilely under alkaline environment, and reduction of the nitro groups produced the desired amidobenzene-containing hemicucurbituril. As an original fluorescent chemosensor, it exhibited strong interactions with Fe3+ over other metal cations. The experimental evidence of fluorescence spectra suggested that a 1:1 complex was formed between this macrocycle and Fe3+ with an association constant up to (2.1 ± 0.3) × 104 M-1. Meanwhile, this macrocycle showed no obvious or only slight enhancement of the fluorescence intensity with selected anions.

Study on the interactions between melamine-cored Schiff bases with cucurbit[n]urils of different sizes and its application in detecting silver ions.

Three different complexes, TMeQ[6]-TBT, Q[7]-TBT, and Q[8]-TBT are constructed by three different cucurbiturils and synthesized by guest melamine-cored Schiff bases (TBT) through outer-surface interaction and host-guest interactions. TBT forms a TMeQ[6]-TBT complex with TMeQ[6] through outer-surface interaction, while Q[7]-TBT and Q[8]-TBT form complexes with Q[7,8] through host-guest interactions. Among them, Q[7]-TBT is selected as a UV detector for the detection of silver ions (Ag+). This work makes full use of the characteristics of each cucurbituril and melamine-cored Schiff base to construct a series of complexes and these are applied to metal detection.

Effects of Photoperiod on Acetaminophen-Induced Hepatotoxicity in Mice.

PURPOSE: Acetaminophen (APAP) is a clinically popular analgesic and antipyretic drug, but excessive APAP can cause fatal hepatotoxicity. Many factors affect the degree of APAP-induced liver injury. This study aimed to investigate how circadian rhythm affects the development of APAP-induced hepatotoxicity and to clarify the roles of photoperiod and dietary rhythm on APAP-induced hepatotoxicity in mice. METHODS: APAP-induced hepatotoxicity models were established by intraperitoneal injection of APAP (400 mg/kg) to mice. The mice were then divided into three treatment groups: normal diet, reversed diet, and reversed photoperiod. RESULTS: More severe liver injury was observed at zeitgeber time 12 (ZT12) than at zeitgeber time 0 (ZT0) in all treatment groups, suggesting that photoperiod played a critical role in APAP-induced liver injury. We observed a change in the expression of the circadian gene Per2, which may be responsible for regulation of liver injury by photoperiod. Our results showed negligible change in Per2 expression with diet reversion, whereas Cry1, Cry2, and Dbp expressions were more highly affected by diet reversion than was Per2 expression. Downstream effects including liver enzyme expression, GSH level, and inflammation factors were also examined to identify the mechanism of liver injury. The results indicated that the circadian gene Per2 participated in APAP biometabolism by regulating the expression of Cyp2e1, which may explain the more severe hepatotoxicity at ZT12 than at ZT0. CONCLUSION: APAP-induced hepatotoxicity can be mediated by photoperiod through the circadian gene Per2, suggesting that medicines containing APAP should be administered not only with food but also according to the appropriate photoperiod.

Microsomal prostaglandin E synthase 2 deficiency is resistant to acetaminophen-induced liver injury.

Acetaminophen (APAP)-induced liver injury is the main cause of acute liver failure. This study investigated the role of microsomal prostaglandin E synthase 2 (mPGES-2), discovered as one of the prostaglandin E2 (PGE2) synthases, in mediating APAP-induced liver injury. Using mPGES-2 wild-type (WT) and knockout (KO) mice, marked resistance to APAP-induced liver damage was found in mPGES-2 KO, as indicated by robust improvement of liver histology, changes in liver enzyme release, and marked decrease in APAP-cysteine adducts (APAP-CYS) and inflammatory markers. Moreover, the results confirmed that increase in liver PGE2 content in KO mice under basal conditions was not critical for the protection from APAP-induced liver injury. Importantly, mPGES-2 deletion inhibited the production of malondialdehyde (MDA), increasing glutathione (GSH) level. Enhanced GSH level may contribute to the inhibition of APAP toxicity in mPGES-2 KO mice. To further elucidate the role of mPGES-2 in the liver injury induced by APAP, adeno-associated viruses (AAV) were used to overexpress mPGES-2 in the liver. The results showed that mPGES-2 overexpression aggravates liver injury associated with an increase in inflammatory markers and chemokines after APAP treatment. Moreover, a lower level of GSH was detected in the mPGES-2 overexpression group compared to the control group. Collectively, our findings indicate that mPGES-2 plays a critical role in regulating APAP-induced liver injury, possibly by regulating GSH and APAP-CYS level, which may provide a potential therapeutic strategy for the prevention and treatment of APAP-induced liver injury.

Mangiferin ameliorates acetaminophen-induced hepatotoxicity through APAP-Cys and JNK modulation.

An overdose of the most popular analgesic, acetaminophen (APAP), is one of the leading causes of acute liver failure. It is well established that glutathione is exhausted by APAP-reactive intermediate N­acetyl­p­benzoquinone-imine (NAPQI). This leads to elevated phosphorylated-c-Jun N-terminal kinase (p-JNK), which further activates reactive oxygen species (ROS), initiates an inflammatory response, and finally leads to severe hepatic injury. The present study was conducted to investigate the protective role of mangiferin (MAN), a naturally occurring xanthone and anti-oxidant, on APAP-induced hepatotoxicity. C57BL/6 mice were pretreated with or without MAN at 1 h prior to APAP challenge. MAN was administered at a dose of 12.5-50 mg/kg along with APAP at a dose of 400 mg/kg. According to the ALT/AST ratio, 25 mg/kg MAN was the most potent dose for further experiments. Serum ALT and AST depletion were observed in APAP + MAN (25 mg/kg)-treated mice at 6, 12, and 24 h. Early (1 h after APAP treatment) GSH depletion by APAP overdose was restored by MAN treatment, which reduced APAP-Cys adduct formation and promoted protection. p-JNK downregulation and AMPK activation were observed in MAN-treated mice, which could mechanistically reduce oxidative stress and inflammation. MAN up-regulated liver GSH and SOD and reduced lipid peroxidation. HO-1 protein and p47 phox mRNA expression indicated that MAN regulated oxidative stress along with JNK deactivation. The expression of inflammatory response genes TNF-α, IL-6, MCP-1, CXCL-1, and CXCL-2 reached the basal levels after MAN treatment. mRNA, protein, and serum levels of IL-1ß were reduced, and NF-κB expression was similar to that of the MAN-treated APAP mice. MAN post-treatment (1 h after APAP treatment) also protected the mice from hepatotoxicity. In conclusion, MAN had a protective and therapeutic role in APAP-induced hepatotoxicity by improving the metabolism of acetaminophen and APAP-Cys adduct formation followed by JNK-mediated oxidative stress and inflammation.

A Novel Prebiotic Blend Product Prevents Irritable Bowel Syndrome in Mice by Improving Gut Microbiota and Modulating Immune Response.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder yet it still lacks effective prevention therapies. The aim of this study is to determine whether a novel prebiotic blend (PB) composed of fructo-oligosaccharide (FOS), galactooligosaccharide (GOS), inulin and anthocyanins could be effective in preventing the development of IBS. We explored the possible mechanisms both in animal and in cells. Post-infectious IBS models in C57BL/6 mice were established and were pretreated with the PB, PB and probiotic strains 8 weeks in advance of infection. Eight weeks after infection, intestinal tissues were collected for assessing histomorphology, visceral sensitivity, barrier function, pro-inflammatory cytokines expression and proteomics analysis. Fecal samples were also collected for microbiota analysis. The pro-inflammatory cytokines expression in Caco-2 cells were evaluated after co-incubation with PB and Salmonella typhimurium 14028. The results showed that PB significantly decreased the pro-inflammatory cytokines both in infected Caco-2 cells and PI-IBS models. The loss of body weight, decreased expression of tight junction protein Occludin (OCLN), and changes of the microbiota composition induced by infections could be greatly improved by PB intervention (p < 0.05). The proteomics analysis revealed that this function was associated with Peroxisome proliferator-activated receptor (PPAR)γ pathway.

Fast onset of action of sublingual immunotherapy in house dust mite-induced allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVES/HYPOTHESIS: To investigate how quickly an allergic rhinitis (AR) patients' symptoms will improve with sublingual immunotherapy (SLIT). STUDY DESIGN: Double-blind placebo study. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled study of SLIT used to treat house dust mite-induced AR. A total of 120 AR patients, aged 4 to 60 years, were treated for 6 months and randomized into two groups: 1) SLIT with Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farina (D.f.) extract (n = 60) ; and 2) matched placebo controls (n = 60). Symptom, medications received, and a visual analog scale score were recorded during the whole study. Serum-specific IgE and IgG4 to D. p. and D. f. were assessed before and after the treatment. RESULTS: Eighty-five patients (70.8%) completed the study. Twelve patients (20%) chose to withdraw from the SLIT group, but none because of serious adverse effects. The total symptom and visual analog scores VAS in the SLIT group decreased significantly when compared to the placebo controls (P <0.05) after week 14, as well as for the significant (P <0.05) improvement of all individual AR symptoms in the SLIT group (e.g., sneezing, nasal discharge, itching, and nasal obstruction) after week 22. There was a significant (P <0.05) increase of IgG4 to both D.f. and D.p. in the SLIT, but not in the placebo group after treatment. CONCLUSION: SLIT with a mixture of D.f. and D.p. extract is an effective and safe treatment for patients with house dust mite-induced AR. Its onset of action can be observed as early as 14 weeks after treatment.

[Maturation of Cordyceps sinensis associates with alterations of fungal expressions of multiple Ophiocordyceps sinensis mutants in stroma of Cordyceps sinensis].

OBJECTIVE: To examine maturational changes in expressions of Ophiocordyceps sinensis (O.sinensis) transition and transversion mutation genotypes in Cordyceps sinensis (C.sinensis) stroma. METHODS: MassARRAY single nucleotide polymorphism (SNP) matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrum genotyping was used, and 8 SNP extension primers were designed based on the scattered, multiple point mutations of known sequences for the O.sinensis mutants within their internal transcribed spacer (ITS) segments. Of the extension primers, 5 (not capable of distinguishing between the 2 AT-biased genotypes) located in rDNA ITS1 and ITS2 regions: 067721-211, 067721-240, 067721-477, 067721-531 and 067721-581. The other 3 extension primers located in 5.8S rDNA region: 067740-324, 067740-328 and 067740-360, to distinguish between the 2 AT-biased genotypes. RESULTS: MS chromatograms at the 8 SNP sites showed dynamic alterations of mutant alleles in C.sinensis stroma. The allele for the AT-biased genotypes at 067721-211 site showed higher peak height than its GC-biased counterpart in the premature C.sinensis stroma, but disappeared with C.sinensis maturation. Chromatograms displayed not only the transition mutation alleles, but also transversion mutants. Some of the transversion mutation alleles displayed higher peak heights than those for GC- and AT-biased alleles, but their peak heights and detection rates tended to be decreased with C.sinensis maturation. When distinguishing between the 2 AT-biases, AB067744 and AB067740 genotype alleles co-existed in the premature C.sinensis stroma. The allele peak height for AB067744 genotype was greatly decreased with C.sinensis maturation, while that for AB067740 genotype increased. CONCLUSION: Co-existence of at least 5 transition and transversion mutant genotypes of O.sinensis and the dynamic changes in their expressions in C.sinensis stroma along with C.sinensis maturation may be of extreme importance in C.sinensis stroma germination and maturation, enabling C.sinensis to complete its life cycle.

[Detection of multiple Ophiocordyceps sinensis mutants in premature stroma of Cordyceps sinensis by MassARRAY SNP MALDI-TOF mass spectrum genotyping].

OBJECTIVE: To examine the mutants of Ophiocordyceps sinensis (Os) in the stroma of premature Cordyceps sinensis (Cs). METHODS: Used MassARRAY single nucleotide polymorphism (SNP) MALDI-TOF mass spectrum genotyping, designed eight SNP extension primers on the basis of the scattered, multiple point mutations of known Os mutants within their internal transcribed spacer (ITS) segments, and examined the Os mutant genotypes relating to the GC-biased Os genotype (gb #AB067721) in premature Cs stroma. RESULTS: The two AT-biased genotypes and the GC-biased Os were simultaneously detected in premature Cs stroma. SNP genotyping also detected at least two other Os genotypes of unknown sequences. CONCLUSION: Coexistence of the three known Os genotypes indicates the existence of possible transition point mutations within Os genes during germination and early maturation of Cs. Simultaneous detection of at least two unknown genotypes coexisting with those known mutants possibly evidences the transversion mutations within Os genes.

[Clinical efficacy of subcutaneous and sublingual immunotherapy in mite-sensitized patients with allergic rhinitis].

OBJECTIVE: To investigate the clinical efficacy of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for persistent allergic rhinitis (PER). METHODS: Ninety-eight patients with moderate to severe PER caused by HDM and who completed SCIT (Alutard SQ, ALK-Abell¨®) or SLIT (Chanllergen-Df drops, Wolwo Pharma) regimen for two years were enrolled in this open-label controlled study. The patients were divided into two groups: SCIT group consisted of 40 patients aged 7 to 57 years old [(19.0 ± 2.7) years, x(-) ± s], and SLIT group consisted of 58 patients aged 6 to 50 years old [(17.7 ± 3.2) years]. The nasal symptoms (sneezing, rhinorrhea, nasal obstruction and pruritus) were evaluated using a four-point rating scale (from 0 = absent to 3 = severe) as well as 10 cm-visual analogue scale (VAS). Efficacy of SCIT and SLIT was assessed as the mean change from baseline in nasal symptom scores after 2-year course of immunotherapy, and the results were compared. SAS software version 9.1.3 was applied for statistical analysis. RESULTS: Both SCIT and SLIT significantly reduced the individual symptom score of sneezing, rhinorrhea, nasal obstruction and pruritus, and the total nasal symptom scores (including 4-point scale and VAS) after 2-year treatment when compared with the baseline (Z value were -3.14, -3.76, -3.09, -3.48, -4.13; -3.63, -3.21, -2.48, -3.56, -3.98, respectively, all P < 0.05). There was no significant difference in decreased mean score of the individual and total nasal symptoms (4-point scale) between SCIT and SLIT groups (Z value were -0.97, -0.67, -0.36, -0.04, -0.67, respectively, all P > 0.05). However, a significant reduction of VAS score of nasal obstruction was found in SCIT group after 2-year treatment, compared with SLIT group (t = -2.21, P = 0.032). There was no significant difference in decreased VAS score of three other nasal symptoms as well as global rhinitis severity between two immunotherapy groups (t value were -0.57, -1.93, -1.73, -0.99, respectively, all P > 0.05). CONCLUSIONS: Both SCIT and SLIT demonstrated clinical improvement in moderate to severe PER patients sensitized to HDM after two years treatment. It is suggested that SCIT may relieve nasal obstruction significantly; however, the overall clinical efficacy is consistent with SCIT and SLIT.

[Compliance and safety evaluation of subcutaneous versus sublingual immunotherapy in mite-sensitized patients with allergic rhinitis].

OBJECTIVE: To investigate the safety profile of subcutaneous immunotherapy (SCIT) versus sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) caused by house dust mites. The treatment compliance and related factors were also evaluated. METHODS: A total of 160 patients with AR were enrolled in this study and received either SCIT (Alutard SQ, ALK-Abelló) or SLIT (Chanllergen-Df drops, Wolwo Pharma). All subjects were divided into two groups: SCIT group consisted of 81 patients aged 7 to 62 years [(21.5 ± 14.6) years, x ± s], and SLIT group consisted of 79 patients aged 6 to 53 years [(15.1 ± 10.3) years]. The selected patients were persistent and moderate to severe AR sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Local and systemic reactions, as well as patient's adherence to the treatment, were carefully recorded and analyzed during the immunotherapy schedules (followed up for 6 months to 2 years). Statistical analysis was performed using a SPSS13.0 software. RESULTS: Local swelling commonly occurred following injections throughout the treatment duration (62.9% of overall injections) in the SCIT group. Oral itching associated with drop intakes was reported by 4 subjects (5.1%) in the SLIT group. All local reactions were mild, well tolerated and self-limiting in both groups. A total of 11 patients (13.6%) with 18 injections (0.9%) experienced systemic reactions in the SCIT group, involving respiratory distress, asthmatic attacks, and urticaria. These adverse effects were mostly immediate reactions, and occurred more frequently in patients during the maintenance phase of treatment. There were also 11 patients (13.9%) who experienced systemic reactions in the SLIT group, including gastrointestinal symptoms, urticaria, and rhinitis exacerbations. However, systemic reactions to SLIT were mainly observed in patients during the up-dosing phase of treatment. No significant difference in the overall incidence of systemic adverse effects was found between the SCIT and SLIT groups (13.6% and 13.9% respectively, χ(2) = 0.004, P > 0.05). There was only one case of non-life-threatening systemic reaction (severe asthma) in the SCIT group. Others were mild or moderate and no anaphylactic shock occurred in any group. No significant difference in treatment compliance was found between the SCIT and SLIT groups (86.4% and 79.7% respectively, χ(2) = 0.84, P > 0.05), with an overall rate of compliance (83.1%) among 160 patients. The most common cause for treatment withdrawal was insufficient ineffectiveness, in both groups of SCIT (6.2%) and SLIT (10.1%). CONCLUSION: The results suggest that the frequency of systemic adverse effects of SCIT is not significantly different from SLIT in mite-sensitized patients with AR, and both treatments are well tolerated and had favorable compliance during the study period.