Improving Clinical Outcomes: Hightibialosteotomy Plate Placement Combined with Arthroscopic Surgery.

Objective: Our study aimed to investigate the clinical efficacy of hightibialosteotomy (HTO) posterior plate placement combined with arthroscopic surgery for degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower extremity, improve joint function or relieve pain. Methods: The case data of 98 patients with osteoarthritis of the knee admitted to the Department of Orthopedics in our hospital from January 2019 to January 2023 were selected for retrospective analysis. The patients were divided into 54 patients, each in the study group and the comparison group according to the different treatment regimens. The study group received hightibialosteotomy plate placement combined with arthroscopic surgery, while the comparison group underwent hightibialosteotomy plate placement alone. The differences in knee scores, knee Lysholm scores, Lysholm scores, Healthcare Security and Safety (HSS) scores, Tegner scores, Visual Analog Scale (VAS), lower extremity force lines, femorotibial angles, and tibial plateau were counted and compared between the two groups. Results: HSS knee function scores, Lysholm scores, and VAS scores of the study group were statistically significant compared with those of the comparison group at the final follow-up of patients, and the postoperative clinical outcomes improved significantly (P < .05). The differences in Hip-Knee-Ankle(HKA) angle andMedial-Pateral Tibial Angle (MPTA) of patients in the study group were statistically significant compared with the comparison group, and the increase in HKA (12.31±2.13)°, MPTA (11.84±2.32)° and lower limb force line was significantly improved (P < .05). Preoperatively, there was no statistically significant comparison between the visual analog scores of the knee joint in the study group and the comparison group. After surgery, the difference between the two groups was statistically significant (P < .05). The relative position of the mechanical axis of the lower limb through the tibial plateau, the femorotibial angle, and the posterior tibial plateau angle increased in patients after surgery, and the differences were statistically significant when compared with the preoperative period (P < .05). Both the tibial posterior displacement distance and the lateral knee gap opening were reduced compared with the preoperative period, and the differences were statistically significant (P < .05). Conclusion: Hightibialosteotomy after plate placement combined with arthroscopic surgery has better clinical efficacy in the early stage and can effectively treat the degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower limb, improve the joint function, and relieve the symptoms of patients.

MODMS: a multi-omics database for facilitating biological studies on alfalfa (Medicago sativa L.).

Alfalfa (Medicago sativa L.) is a globally important forage crop. It also serves as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Multi-omics data on alfalfa continue to accumulate owing to recent advances in high-throughput techniques, and integrating this information holds great potential for expediting genetic research and facilitating advances in alfalfa agronomic traits. Therefore, we developed a comprehensive database named MODMS (multi-omics database of M. sativa) that incorporates multiple reference genomes, annotations, comparative genomics, transcriptomes, high-quality genomic variants, proteomics, and metabolomics. This report describes our continuously evolving database, which provides researchers with several convenient tools and extensive omics data resources, facilitating the expansion of alfalfa research. Further details regarding the MODMS database are available at https://modms.lzu.edu.cn/.

Dietary lysolecithin supplementation improves growth performance of weaned piglets via improving nutrients absorption, lipid metabolism, and redox status.

Lysolecithin is widely used as emulsifier to improve the digestibility and retention of fat. The current study aimed to investigate the effects of dietary lysolecithin supplementation on growth performance, nutrients absorption, lipid metabolism, and redox status of weaned pigs. A total of 60 weaned piglets were assigned into 2 dietary treatments in a randomized complete block design, receiving basal diet with 0 or 1,000 mg/kg lysolecithin for a period of 28 d. Each dietary treatment had 10 replicates with 3 piglets per replicate. Growth performance and fecal score were monitored during trial. Samples of blood, ileum, and liver tissues were collected and analyzed for serology, intestinal histomorphology, and lipid metabolism-related gene and protein expressions. Dietary lysolecithin supplementation increased average daily gain (+15%, P < 0.05) and tended to increase average daily feed intake (+14%, P = 0.08) in overall experimental period. At final, the average body weight of piglets in lysolecithin group was 10% greater than that of control group (P = 0.09). In addition, dietary lysolecithin supplementation improved the ability of nutrients absorption as indicated by the higher d-xylose level in plasma (P < 0.05). Moreover, piglets from lysolecithin group had higher concentration of high-density lipoprotein (P < 0.05), but lower triglyceride (P < 0.05) in plasma. The inclusion of lysolecithin in diet increased the level of reduced glutathione (GSH) and GSH to oxidized glutathione (GSSG) ratio in plasma and liver (P < 0.05), but attenuated the levels of malondialdehyde and GSSG in ileum (P < 0.05). The upregulation of lipogenesis-related genes (FAS and ACC), downregulation of lipolysis (PNPLA2 and PABP1), and lipid mobilization (PGC-1α and SRIT1) genes were observed in lysolecithin relative to control piglets. Compared with control group, dietary lysolecithin supplementation upregulated protein expressions of GPX4, SREBP1, and LPL in liver and LPL in ileum (P < 0.05). Collectively, our study indicates that dietary lysolecithin supplementation improved growth performance of weaned piglets, which may be associated with the improved nutrients absorption, redox status, and lipid metabolism.

Early weaning has been widely adopted to maximize productivity for swine production. However, the weaned piglets suffer from insufficient energy intake due to the reduced feed intake caused by weaning stress, which compromises the growth rate of piglets. In the present study, dietary lysolecithin supplementation increased average daily gain and average daily feed intake in overall experimental period, thereby showed positive effect on final body weight of weaned piglets. In addition, lysolecithin supplementation improved adipogenesis and anti-oxidant capacity, but suppressed lipolysis and pro-oxidant factors.

Targeting Alpha-Ketoglutarate Disruption Overcomes Immunoevasion and Improves PD-1 Blockade Immunotherapy in Renal Cell Carcinoma.

The Warburg effect-related metabolic dysfunction of the tricarboxylic acid (TCA) cycle has emerged as a hallmark of various solid tumors, particularly renal cell carcinoma (RCC). RCC is characterized by high immune infiltration and thus recommended for immunotherapeutic interventions at an advanced stage in clinical guidelines. Nevertheless, limited benefits of immunotherapy have prompted investigations into underlying mechanisms, leading to the proposal of metabolic dysregulation-induced immunoevasion as a crucial contributor. In this study, a significant decrease is found in the abundance of alpha-ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Elevated levels of αKG promote major histocompatibility complex-I (MHC-I) antigen processing and presentation, as well as the expression of ß2-microglobulin (B2M). While αKG modulates broad-spectrum demethylation activities of histone, the transcriptional upregulation of B2M is dependent on the demethylation of H3K4me1 in its promoter region. Furthermore, the combination of αKG supplementation and PD-1 blockade leads to improved therapeutic efficacy and prolongs survival in murine models when compared to monotherapy. Overall, the findings elucidate the mechanisms of immune evasion in anti-tumor immunotherapies and suggest a potential combinatorial treatment strategy in RCC.

Paraventricular Thalamus Dynamically Modulates Aversive Memory via Tuning Prefrontal Inhibitory Circuitry.

The impact of stress on the formation and expression of memory is well studied, especially on the contributions of stress hormones. But how stress affects brain circuitry dynamically to modulate memory is far less understood. Here, we used male C57BL6/J mice in an auditory fear conditioning as a model system to examine this question and focused on the impact of stress on dorsomedial prefrontal cortex (dmPFC) neurons which play an important role in probabilistic fear memory. We found that paraventricular thalamus (PVT) neurons are robustly activated by acute restraining stress. Elevated PVT activity during probabilistic fear memory expression increases spiking in the dmPFC somatostatin neurons which in turn suppresses spiking of dmPFC parvalbumin (PV) neurons, and reverts the usual low fear responses associated with probabilistic fear memory to high fear. This dynamic and reversible modulation allows the original memory to be preserved and modulated during memory expression. In contrast, elevated PVT activity during fear conditioning impairs synaptic modifications in the dmPFC PV-neurons and abolishes the formation of probabilistic fear memory. Thus, PVT functions as a stress sensor to modulate the formation and expression of aversive memory by tuning inhibitory functions in the prefrontal circuitry.SIGNIFICANCE STATEMENT The impact of stress on cognitive functions, such as memory and executive functions, are well documented especially on the impact by stress hormone. However, the contributions of brain circuitry are far less understood. Here, we show that a circuitry-based mechanism can dynamically modulate memory formation and expression, namely, higher stress-induced activity in paraventricular thalamus (PVT) impairs the formation and expression of probabilistic fear memory by elevating the activity of somatostatin-neurons to suppress spiking in dorsomedial prefrontal parvalbumin (PV) neurons. This stress impact on memory via dynamic tuning of prefrontal inhibition preserves the formed memory but enables a dynamic expression of memory. These findings have implications for better stress coping strategies as well as treatment options including better drug targets/mechanisms.

Analysis of chemical constituents of Sabia parviflora by ultrahigh performance liquid chromatography quadrupole time of flight tandem mass spectrometry.

Effective and targeted identification of chemical components of the Chinese herbal medicine Sabia parviflora remains a major challenge. Herein, we used ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to analyze the chemical composition of S.parviflora. Its chemical components were rapidly identified using the characteristic ion filtration method, which involves these steps: (1) summarize the characteristic ions based on similar skeletons and compounds with substitution patterns, and establish a database; (2) screen and classify different types of compounds in S. parviflora based on the characteristic ions; and (3) identify the compounds based on molecular weight, secondary fragments, and the database. In the present study, the characteristic ions in S. parviflora were grouped into five major classes. A total of 104 components were identified, including 12 potentially novel compounds. This rapid and accurate method provides an important basis for basic chemical research in S. parviflora.

Exploring the Regulation of Jiangtang Tiaozhi Formula on the Biological Network of Obese T2DM Complicated With Dyslipidemia Based on Clinical Transcriptomics.

Objective: To use systems biology to explore the biomolecular network mechanism of the Jiangtang Tiaozhi Recipe (JTTZR) in the intervention of obese Type 2 diabetes (T2DM) patients with dyslipidemia. Methods: Twelve patients with obese type 2 diabetes mellitus and dyslipidemia (traditional Chinese medicine syndrome differentiation was excess heat syndrome of the stomach and intestines) were treated with JTTZR for 24 weeks, and 12 patients were included in the healthy control group. First, blood samples from 6 patients in each group (disease group before treatment, disease group after treatment, and healthy control group) were collected for RNA microarray analysis. Quantitative polymerase chain reaction (qPCR) was used to validate these target lncRNAs and mRNAs. Finally, a detailed analysis of the differences in the disease group before treatment vs. the healthy control group and the disease group after treatment vs. the disease group before treatment was undertaken. In addition, we focused on disease-related pathways and analyzed the correlation between the differential expression of target lncRNAs and clinical indicators. Results: (1) Disease group before treatment vs. healthy control group: There were 557 up-regulated lncRNAs, 273 down-regulated lncRNAs, 491 up-regulated mRNAs, and 1639 down-regulated mRNAs. GO analysis and pathway analysis showed that T2DM may be related to cell proliferation in the forebrain, post-embryonic organ development, calcium signaling pathway. qPCR validation showed that the expression of XLOC-005590 and HNF1A-AS1 as target lncRNAs increased, and this was verified by gene chip analysis. (2) Disease group after treatment vs. disease group before treatment: 128 lncRNAs were upregulated, 32 lncRNAs were downregulated, 45 mRNAs were upregulated, and 140 mRNAs were downregulated. GO analysis and pathway analysis showed that JTTZR may treat T2DM through endosome transport, the insulin signaling pathway, and glycine, serine, and threonine metabolism. qPCR validation showed that in the healthy control group, XLOC_005590 was upregulated, whereas the downstream gene (ECI2) was downregulated in the disease group before treatment. However, after 24 weeks of intervention with JTTZR, XLOC_005590 was downregulated and ECI2 was upregulated compared with the disease group before treatment (0 weeks) (P <0.05). Conclusion: JTTZR may interfere in patients with obese T2DM with dyslipidemia by regulating pathways such as fatty acid degradation, glycolysis/gluconeogenesis, and pyruvate metabolism.

Efficacy of ω-3 Polyunsaturated Fatty Acids in Patients with Lung Cancer Undergoing Radiotherapy and Chemotherapy: A Meta-Analysis.

Background: Radiotherapy and chemotherapy in patients with lung cancer can lead to a series of problems such as malnutrition and inflammatory reaction. Some studies have shown that ω-3 polyunsaturated fatty acids (PUFAs) could improve malnutrition and regulate inflammatory reaction in these patients, but no relevant meta-analysis exists. Methods: We systematically searched randomized controlled trials of ω-3 PUFAs in the adjuvant treatment of lung cancer in the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang databases. Relevant outcomes were extracted, and we pooled standardized mean differences (SMDs) using a random or fixed-effects model. The risk of bias was evaluated according to the Cochrane Handbook (version 15.1). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: A total of 7 studies were included. The SMDs (95% CI) of body weight change, albumin change, energy intake, and protein intake at the end of intervention were 1.15 (0.50, 1.80), 0.60 (0.11, 1.09), 0.39 (-0.10, 0.89), and 0.27 (-0.04, 0.58), respectively. The SMDs (95% CI) of CRP change and TNF-α change were -3.44 (-6.15, -0.73) and -1.63 (-2.53, -0.73), respectively. Conclusions: ω-3 PUFAs can improve nutritional status and regulate indicators of inflammation in patients with lung cancer undergoing radiotherapy and chemotherapy. This study was registered in the PROSPERO (registration number: CRD42022307699).

Reduction of psychological cravings and anxiety in women compulsorily isolated for detoxification using autonomous sensory meridian response (ASMR).

OBJECTIVE: To explore the effects of the autonomous sensory meridian response (ASMR) on the psychological cravings and anxiety of women compulsorily isolated for detoxification. METHOD: Around 122 women were recruited in a female drug detoxification center. Except for the 12-week training of ASMR, the experimental conditions of the experimental group (n = 60) were the same as those of the control group (n = 62). The addiction Stroop task was used to assess the level of psychological cravings and the State-Trait Anxiety Inventory was used to assess the level of anxiety. RESULTS: After the training, the decrease in state anxiety of the experimental group was larger than that of the control group, and the reaction time of the experimental group in the Stroop was also significantly lower than before the training. CONCLUSIONS: ASMR could thus reduce to a certain extent the state anxiety and attentional bias for drug-related clues under signaling psychological cravings among women compulsorily isolated for detoxification. HIGHLIGHTS: Intervention effects on psychological cravings and anxiety of women isolated for detoxification Basis for role of ASMR in regulating psychological cravings and anxiety in forced abstainers ASMR intervention reduced forced abstainers' attentional bias to drug-related clues.

A natural product targets BRD4 to inhibit phase separation and gene transcription.

The BET-bromodomain protein BRD4 uses two bromodomains to target acetyl-histones and other domains to recruit P-TEFb and other transcription factors to stimulate transcription of proto-oncogenes and key cell identity genes. Recent studies show that its ability to form phase-separated condensates that cluster preferentially at the super-enhancer regions of target genes is key for BRD4 to exert its functions. Here, we describe the identification of a natural product called PCG from polygonum cuspidatum Sieb.et Zucc., a traditional Chinese medicinal herb, that directly binds to BRD4. This binding inhibits BRD4 phase separation, turns dynamic BRD4 nuclear condensates into static aggregates, and effectively shuts down transcription of BRD4-dependent genes. Thus, through PCG we have discovered a BET inhibitor that not only selectively targets BRD4 but also works by suppressing phase separation, a mechanism of action that is different from those of the other known BET inhibitors.

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches.

Andrographis paniculata (Burm. f.) Wall. ex Nees, a renowned herb medicine in China, is broadly utilized in traditional Chinese medicine (TCM) for the treatment of cold and fever, sore throat, sore tongue, snake bite with its excellent functions of clearing heat and toxin, cooling blood and detumescence from times immemorial. Modern pharmacological research corroborates that andrographolide, the major ingredient in this traditional herb, is the fundamental material basis for its efficacy. As the main component of Andrographis paniculata (Burm. f.) Wall. ex Nees, andrographolide reveals numerous therapeutic actions, such as antiinflammatory, antioxidant, anticancer, antimicrobial, antihyperglycemic and so on. However, there are scarcely systematic summaries on the specific mechanism of disease treatment and pharmacokinetics. Moreover, it is also found that it possesses easily ignored security issues in clinical application, such as nephrotoxicity and reproductive toxicity. Thereby it should be kept a lookout over in clinical. Besides, the relationship between the efficacy and security issues of andrographolide should be investigated and evaluated scientifically. In this review, special emphasis is given to andrographolide, a multifunctional natural terpenoids, including its pharmacology, pharmacokinetics, toxicity and pharmaceutical researches. A brief overview of its clinical trials is also presented. This review intends to systematically and comprehensively summarize the current researches of andrographolide, which is of great significance for the development of andrographolide clinical products. Noteworthy, those un-cracked issues such as specific pharmacological mechanisms, security issues, as well as the bottleneck in clinical transformation, which detailed exploration and excavation are still not to be ignored before achieving integration into clinical practice. In addition, given that current extensive clinical data do not have sufficient rigor and documented details, more high-quality investigations in this field are needed to validate the efficacy and/or safety of many herbal products.

Elucidating the estrogen-like effects and biocompatibility of the herbal components in the Qing' E formula.

ETHNOPHARMACOLOGICAL RELEVANCE: The Qing' E Formula (QEF) is a compound preparation that was originally recorded in the 'Prescriptions of the Bureau of Taiping People's Welfare Pharmacy' during the Song Dynasty (10th century CE). It consists of four Chinese medicinal herbs, Eucommiae Cortex (Eucommia ulmoides), Psoraleae Fructus (Psoralea corylifolium), Juglandis Semen (Juglans regia), and Garlic Rhizoma. According to traditional Chinese medicine (TCM), QEF has the ability to tonify the kidney and strengthen muscle and bone. According to the 'kidney governing bone' theory in TCM, QEF is also used to treat the symptoms of climacteric syndrome, especially osteoporosis caused by reduced production of estrogen during the perimenopausal period; however, the therapeutic roles of the individual components of the QEF and their compatibility within the formula has not been investigated. AIM OF THE STUDY: In this study, the compatibility mechanism and estrogen-like action properties of the four herbal components in the QEF was elucidated according to the organizing principle of Chinese medicine formulas using both in vitro and in vivo models. MATERIALS AND METHODS: The estrogen-like effects of QEF and its herbal components were investigated in MCF7 and HEK293 cells as well as ovariectomized (OVX) rats. The estrogen-like effects of the QEF and its components were analyzed in vitro using Cell Counting Kit-8 and Luciferase reporter gene assays. In the in vivo studies, the blood plasma levels of hormones, lipids, neurotransmitters, aromatase, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured through enzyme-linked immunosorbent assays (ELISAs). The histological morphologies of the target organs after exposure to QEF were investigated by HE staining and immunohistochemical methods. The expression levels of estrogen pathway-related proteins and genes in the OVX rats were measured by Western blotting and real time quantitative PCR (RT-qPCR), respectively. RESULTS: The in vitro results showed that the QEF, Eucommia (EC) and Psoralea (PF) promoted the proliferation of MCF-7 cells and upregulated the expression of ERα, ERß and pS2 genes in the MCF-7 cells. Notably, the QEF demonstrated the most active estrogen-like effects compared to the individual ingredients. The in vivo results showed that the QEF, EC, and PF increased the uterine coefficient, upregulated the expression of both ERs (ERα and ERß) in the uterus, and increased blood serum hormone levels. QEF and its individual components ameliorated menopausal-derived lipid metabolism dysfunction, increased neurotransmitter production by stimulating the adrenal glands, enhanced the antioxidant activity in the serum by increasing the concentration of SOD, reversed ovariectomy-derived atrophy in the uterus, and reduced the weight gain associated with estrogen reduction in the OVX rats. The QEF also antagonize the loss of appetite of OVX animals caused by feeding Psoralea alone, which could explain the compatibility mechanism of Qing' E Formula with reducing toxicity and increasing efficiency. CONCLUSIONS: The estrogen-like effects of Eucommia and Psoralea were mainly mediated through activation of ERα and ERß. The phytoestrogen components regulated hormone production and the expression of related proteins and genes, which indicated that these components exhibited estrogen-like therapeutic effects. However, the QEF showed the greatest estrogen-like effects compared to the individual components. Overall, this corroborated the therapeutic prowess of the QEF and clarified the pharmacodynamic interactions between the different components extracts in the QEF.

Xueshuantong Improves Functions of Lymphatic Ducts and Modulates Inflammatory Responses in Alzheimer's Disease Mice.

Recent studies have revealed significant contributions of lymphatic vessels (LVs) to vital functions of the brain, especially related to clearance of waste from the brain and immune responses in the brain. These studies collectively indicate that enhancing the functions of LVs may improve brain functions during brain aging and in Alzheimer's disease (AD) where LV functions are impaired. However, it is currently unknown whether this enhancement can be achieved using small molecules. We have previously shown that a widely used Chinese herbal medicine Xueshuantong (XST) significantly improves functions and reduces pathology in AD transgenic mice associated with elevated cerebral blood flow (CBF). Here, we show that XST partially rescues deficits in lymphatic structures, improves clearance of amyloid-ß (Aß) from the brain, and reduces the inflammatory responses in the serum and brains of transgenic AD mice. In addition, we showed that this improvement in the lymphatic system occurs independently of elevated CBF, suggesting independent modulation and limited interaction between blood circulation and lymphatic systems. Moreover, XST treatment leads to a significant increase in GLT-1 level and a significantly lower level of MMP-9 and restores AQP4 polarity in APP/PS1 mice. These results provide the basis for further exploration of XST to enhance or restore LV functions, which may be beneficial to treat neurodegenerative diseases or promote healthy aging.

Application of WALANT technique for repairing finger skin defect with a random skin flap.

BACKGROUND: Wide-awake local anesthesia no tourniquet (WALANT) technique has emerged among hand surgeons with other indications. Surgeries involving pedicled flap and revascularization are no longer used as contraindications. The present study aimed to evaluate the feasibility and merits of the WALANT technique in random skin flap surgery. METHODS: From May 2018 to March 2019, 12 patients with finger skin defects repaired with random skin flaps were reviewed. Abdominal skin flaps or thoracic skin flaps were used to cover the wound. Both the fingers and the donor sites were anesthetized by the WALANT technique. A 40-mL conventional volume consisted of a mixture of epinephrine and lidocaine. A volume of 5 mL was injected at the distal palmar for nerve block, the other 5 mL was injected around the wound for hemostasis, and the remaining was injected at the donor site of flaps for both analgesia and hemostasis. Baseline data with respect to sex, age, side, type of finger, donor sites, flap size, dosage of anesthetics, usage of finger tourniquet, intraoperative and postoperative pain, hemostasis effect, operation time, Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH) score, and hospitalization expense, were collected. RESULTS: All patients tolerated the procedure, and none of them needed sedation. Single finger skin defect in 8 patients and double finger skin defect occurred in 4 patients; 5 patients were repaired by abdominal skin flaps, and 7 patients were repaired by thoracic skin flaps. The good surgical field visibility was 91.7%. All flaps survived adequately, without necrosis, pulling fingers out, and other complications. The average visual analog scale (VAS) score of the maximal pain was 1.1 in fingers vs. 2.1 in donor sites during the operation. On postoperative day one, the average VAS score of the maximal pain in fingers and donor sites was 1.3 and 1.1, respectively. The average hospitalization expense before reimbursement of the whole treatment was 11% less expensive compared to the traditional method. The average QuickDASH score was 9.1. CONCLUSIONS: Under wide-awake anesthesia, patients have the ability to control their injured upper extremities consciously, avoiding the complications due to pulling flap pedicles. With the merits of safety, painlessness, less bleeding, and effectivity, the WALANT technique in random skin flaps is feasible and a reliable alternative to deal with finger skin defect.

Efficacy of Shenlingbaizhu formula on irritable bowel syndrome: a systematic review.

OBJECTIVE: To evaluate the effectiveness and safety of a Shenlingbaizhu (SLBZ) formula in the treatment of irritable bowel syndrome (IBS). The effectiveness of SLBZ with or without conventional treatment was compared to that of conventional treatment alone. METHODS: A comprehensive literature search of four Chinese electronic databases, three English language databases, and two English language trial registries from inception to June 2019 was performed. Two authors independently screened the citations and retrieved full publications of randomized trials on the use of SLBZ with or without conventional treatment for IBS. The methodological quality of the trials was assessed with the Cochrane Collaboration's tool for assessing the risk of bias. Data were extracted and subjected to Meta-analysis to compare the efficacy of the SLBZ formula with or without conventional treatment to conventional treatment alone. RESULTS: Thirteen trials (comprising a total of 868 patients with IBS) were included in this review. The risk of bias of all 13 included trials was assessed as moderate. The SLBZ formula was associated with significant improvements in cure rate [relative risk (RR) score of 2.38, 95% confidence interval (CI) 1.43 to 3.95, I 2 = 0%; 8 trials, n = 487, fixed-effects model (FEM)], diarrhea severity score [mean difference (MD) score of －0.62, 95% CI －1.05 to －0.20, I 2 = 88%; 4 trials, n = 286, random effects model (REM)], abdominal pain severity score (MD score of －0.61, 95% CI －0.70 to －0.52, I 2 = 63%; 4 trials, n = 286, FEM), and abdominal distention severity score (MD score of －0.88, 95% CI －1.54 to －0.21, I 2 = 91%; 3 trials, n = 226, REM) compared to the conventional treatment alone. Adverse events were reported in five trials but only one of these indicated any adverse events associated with SLBZ. CONCLUSION: Based on the 13 trials reviewed here, the SLBZ formula with or without conventional treatment appeared to be safe and more effective in improving the cure rate and reducing the severity of diarrhea, abdominal pain, and abdominal distention compared to conventional treatment alone. However, these trials only generated a moderate quality of evidence, and well-designed and high-quality random controlled trials of the SLBZ formula for the treatment of IBS are required to confirm the efficacy of this treatment option.

Immunomodulatory Effect of Lentinan on Aberrant T Subsets and Cytokines Profile in Non-small Cell Lung Cancer Patients.

As a purified active component from traditional Chinese medicine, lentinan administration can be applied as beneficial chemo-immunotherapy for anti-tumor. In this study, the immunomodulatory effects of lentinan on aberrant T subsets and cytokines profile were evaluated for non-small cell lung cancer (NSCLC). Of all NSCLC patients treated with NP chemotherapeutic protocol (combination of vinorelbin and cisplatin), 73 cases were recruited in this retrospective cohort trial study, of which 38 cases received additional lentinan. The changes of aberrant T subsets and cytokines profile were compared between two groups (chemotherapy in combination with lentinan vs. conserved single chemotherapy) by flow cytometry and molecular biology. Higher subset ratio of CD3+CD8+ cytotoxic T cells was confirmed in the peripheral blood of NSCLC patients. Chemo-immunotherapy of lentinan resulted in a significant increase of CD3 + CD56+ NKT cells (15.7 ± 3.1%), compared with 8.6 ± 1.4% of NKT cells in single chemotherapy group, and up-regulated CD3+CD8+ and CD3+CD4+ subsets as well, but caused the decrease of CD4+CD25+ Tregs induction, accompanied by significant alleviation of IL-10 and TGF-ß1, and elevation of IFN-γ, TNF-α, and IL-12 (P < 0.05). It could be confirmed that lentinan could not only enhance the cellular immunity and promote the beneficial of anti-tumor by associated immunotherapy, but also had the ability to inhibit the expansion of immune suppressive Tregs in the NSCLC patients, in whom there was a raised Tregs induction compared to health control. Lentinan-based chemo-immunotherapy is a promising strategy for anti-tumor via enhancing the proliferation of cytotoxic T cells, followed by the elevation of inflammatory chemokines/cytokines. Meanwhile, the percentage of CD4+ CD25+ Tregs is down-regulated, leading to a shift in the inflammatory status from Th2 to Th1 in NSCLC patients treated with lentinan.

Flaxseed oil supplementation improves intestinal function and immunity, associated with altered intestinal microbiome and fatty acid profile in pigs with intrauterine growth retardation.

Flaxseed oil (FO), enriched in n-3 polyunsaturated fatty acids (PUFAs), is an important oil source for intestinal development and health. We aimed to study the different effects of FO versus soybean oil (SO) on growth, intestinal health and immune function of neonates with intrauterine growth retardation (IUGR) using a weaned piglet model. Forty pairs of male IUGR and normal birth weight piglets, weaned at 21 ± 1 d, were fed diets containing either 4% FO or SO for 3 weeks consecutively. Growth performance, nutrient digestibility and intestinal function parameters, immunology and microbiota composition were determined. IUGR led to a poor growth rate, nutrient digestibility and abnormal immunology variables, whereas feeding FO diet improved systemic and gut immunity, as indicated by increased plasma concentration of immunoglobulin G and decreased CD3+CD8+ T lymphocytes, and down-regulated intestinal expression of genes (MyD88, NF-κB, TNF-α, IL-10). Although IUGR tended to decrease villous height, feeding FO diet tended to increase the villi-crypt ratio and up-regulated expressions of tight junction genes (Claudin-1 and ZO-1), together with increased mucosa contents of n-3 PUFAs and a lower Σn-6/Σn-3 ratio. Besides, FO diet decreased the abundance of pathogenic bacteria Spirochaetes, and increased phylum Actinobacteria, and genera Blautia and Bifidobacterium in colonic digesta. Our findings indicate that IUGR impairs growth rate, nutrient digestibility, and partly immunology variables, whereas feeding FO-supplemented diet could improve intestinal function and immunity of both IUGR and NBW pigs, associated with the altered gut microbiome and mucosal fatty acid profile.

The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model.

BACKGROUND: N-methyl-D-aspartate receptor (NMDAR) hypofunction has been proposed to underlie the pathogenesis of schizophrenia. Specifically, reduced function of NMDARs leads to altered balance between excitation and inhibition which further drives neural network malfunctions. Clinical studies suggested that NMDAR modulators (glycine, D-serine, D-cycloserine and glycine transporter inhibitors) may be beneficial in treating schizophrenia patients. Preclinical evidence also suggested that these NMDAR modulators may enhance synaptic NMDAR function and synaptic plasticity in brain slices. However, an important issue that has not been addressed is whether these NMDAR modulators modulate neural activity/spiking in vivo. METHODS: By using in vivo calcium imaging and single unit recording, we tested the effect of D-cycloserine, sarcosine (glycine transporter 1 inhibitor) and glycine, on schizophrenia-like model mice. RESULTS: In vivo neural activity is significantly higher in the schizophrenia-like model mice, compared to control mice. D-cycloserine and sarcosine showed no significant effect on neural activity in the schizophrenia-like model mice. Glycine induced a large reduction in movement in home cage and reduced in vivo brain activity in control mice which prevented further analysis of its effect in schizophrenia-like model mice. CONCLUSIONS: We conclude that there is no significant impact of the tested NMDAR modulators on neural spiking in the schizophrenia-like model mice.

Vitamin D supplementation could reduce the risk of acute cellular rejection and infection in vitamin D deficient liver allograft recipients.

BACKGROUND: Vitamin D regulates the immune system and affects the outcome of allografts. We investigated the mechanisms underlying the preventative potential of vitamin D in acute cellular rejection (ACR) and infection, and determined its effects on the induction of both T cells and complement. METHODS: A total of 141 patients who received a liver allograft at our center between 2012 and 2016 were enrolled in the study and divided into a vitamin D supplementation group (case group, n = 71) and a non-vitamin D supplementation group (control group, n = 70). Serum was collected in the hours prior to transplantation and within the first month of transplantation. We evaluated the relationship between the serum levels of 25-hydroxyvitamin D ACR, infection, T cells, complement, and graft function. Follow-up was conducted until patient death or June 30, 2018. RESULTS: Vitamin D deficiency was an important independent risk factor for ACR. The incidence of ACR, and bacterial and fungal infection was reduced in patients with vitamin D supplementation. The frequency of Treg, Tmemory, T naïve cells and CD8 + CD28+ T cells (CTL) and the level of complement component 3 were related to ACR in the first month after transplantation. This study showed increased numbers of Treg cells and Tmemory cells and decreased numbers of Naïve cells and CTL in the case group. Vitamin D status was significantly associated with mortality. CONCLUSIONS: Vitamin D supplementation is associated with a lower risk of ACR and infection, suggesting that it may promote immune tolerance towards the liver allografts.

The dual-functional memantine nitrate MN-08 alleviates cerebral vasospasm and brain injury in experimental subarachnoid haemorrhage models.

BACKGROUND AND PURPOSE: Cerebral vasospasm and neuronal apoptosis after subarachnoid haemorrhage (SAH) is the major cause of morbidity and mortality in SAH patients. So far, single-target agents have not prevented its occurrence. Memantine, a non-competitive NMDA re3ceptor antagonist, is known to alleviate brain injury and vasospasm in experimental models of SAH. Impairment of NO availability also contributes to vasospasm. Recently, we designed and synthesized a memantine nitrate MN-08, which has potent dual functions: neuroprotection and vasodilation. Here, we have tested the therapeutic effects of MN-08 in animal models of SAH. EXPERIMENTAL APPROACH: Binding to NMDA receptors (expressed in HEK293 cells), NO release and vasodilator effects of MN-08 were assessed in vitro. Therapeutic effects of MN-08 were investigated in vivo, using rat and rabbit SAH models. KEY RESULTS: MN-08 bound to the NMDA receptor, slowly releasing NO in vitro and in vivo. Consequently, MN-08 relaxed the pre-contracted middle cerebral artery ex vivo and increased blood flow velocity in small vessels of the mouse cerebral cortex. It did not, however, lower systemic blood pressure. In an endovascular perforation rat model of SAH, MN-08 improved the neurological scores and ameliorated cerebral vasospasm. Moreover, MN-08 also alleviated cerebral vasospasm in a cisterna magna single-injection model in rabbits. MN-08 attenuated neural cell apoptosis in both rat and rabbit models of SAH. Importantly, the therapeutic benefit of MN-08 was greater than that of memantine. CONCLUSION AND IMPLICATIONS: MN-08 has neuroprotective potential and can ameliorate vasospasm in experimental SAH models.